DOI,Title,Lab Data,Answer,Initial Answer,BLINDED_1,BLINDED_2,BLINDED_1,CoT_response,CoT answer,CoT Grade,DR_response,DR answer,DR grade
10.1056/NEJMcpc2300894,Case 18-2023: A 19-Year-Old Woman with Dyspnea and Tachypnea,"Hemoglobin (g/dl)	 	9.1	 	8.4
Hematocrit (%)	36.0–48.0	31.5	 	28.4
Mean corpuscular volume (fl)	79.0–98.0	66.7	 	66.8
White-cell count (per μl)	350 ,000	15,540	 	15,690
Differential count (%)				
Neutrophils	35–66	72	—	—
Lymphocytes	25–45	20	—	—
Monocytes	 	6	—	—
Eosinophils	 	1	—	—
Platelet count (per μl)	 	745,000	 	620,000
Albumin (g/dl)	3.5–5.2	2.9	 	3.1
Lactate (mmol/liter)†	 	0.2	 	1.3
Erythrocyte sedimentation rate (mm/hr)	—	—	 0	77
C-reactive protein (mg/liter)	—	—	 .0	147.8
Arterial blood gases				
Fraction of inspired oxygen	—	—	—	0.70
pH	—	—	 	7.51
Partial pressure of carbon dioxide (mm Hg)	—	—	 	31
Partial pressure of oxygen (mm Hg)	—	—	 	206",Takayasu’s arteritis.,Takayasu’s arteritis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 19-year-old woman was transferred to this hospital because of respiratory failure.
The patient had been in her usual state of health until 3 weeks before the current presentation, when pain developed in the right shoulder and the right flank. She was evaluated in the emergency department of another hospital and was discharged home after testing for kidney stones and appendicitis was reportedly negative.
Two weeks before the current presentation, dyspnea with exertion and nonproductive cough developed. Six days after the onset of dyspnea and cough, the patient departed on a vacation cruise with her family. During the 8-day trip, dyspnea and cough worsened and prevented her from participating in activities such as swimming and hiking. By the end of the cruise, she had severe dyspnea with walking, and she required the use of a wheelchair during her trip home. After returning to Massachusetts, she presented to the emergency department of the other hospital for evaluation.
Table 1.

Laboratory Data.
The patient reported ongoing cough and progressively worsening dyspnea but no chest pain or hemoptysis. The temporal temperature was 37.1°C, the heart rate 132 beats per minute, the blood pressure 133/47 mm Hg, the respiratory rate more than 40 breaths per minute, and the oxygen saturation 88% while she was breathing ambient air. She appeared ill and had increased work of breathing. A murmur was heard on cardiac examination; other details of the examination are not available. An electrocardiogram (ECG) reportedly showed sinus tachycardia and lateral and precordial T-wave inversions. Urinalysis results and blood levels of glucose, electrolytes, and troponin T were normal, as were the results of liver-function and kidney-function tests; the blood level of N-terminal pro–B-type natriuretic peptide (NT-proBNP) was 24,913 pg per milliliter (reference range, 5 to 125). Other laboratory test results are shown in Table 1. Blood cultures were obtained.
Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material according to a pulmonary embolism protocol, reportedly revealed pericardial and pleural effusions and multifocal lung opacities but no evidence of pulmonary emboli. Point-of-care ultrasonography reportedly revealed a left ventricular ejection fraction of 25%, marked aortic regurgitation, and a possible aortic-root abscess. Supplemental oxygen was administered through a high-flow nasal cannula. Treatment with intravenous furosemide, vancomycin, ceftriaxone, and azithromycin was started. The patient was transferred to the cardiac intensive care unit of this hospital.
On arrival at the cardiac intensive care unit, the patient received bilevel positive airway pressure. A family member accompanying the patient provided additional history. The patient had had intermittent back pain beginning 6 months before the current presentation. Two months before the current presentation, she had had asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Five weeks before the current presentation, she had had a dental cleaning. During the cruise, the patient had two episodes of diarrhea without fever or chills; the family member did not know whether other persons on the cruise had been ill. The patient had told her family that she had noticed visible pulsations in her chest during the 2 weeks before the current presentation, and the family member reported that the patient’s breathing had appeared labored while she was sleeping.
Other medical history included anxiety and anemia. The patient took supplemental iron and had no known drug allergies. She did not use alcohol, tobacco, or other substances. She lived with her family in Massachusetts and worked in child care. There was no family history of cardiac or autoimmune disease.
The temporal temperature was 36.8°C, the heart rate 118 beats per minute, the blood pressure 145/58 mm Hg in the right arm and 136/65 mm Hg in the left arm, the respiratory rate 48 breaths per minute, and the oxygen saturation 100% while the patient was receiving bilevel positive airway pressure (fraction of inspired oxygen, 0.70). The body-mass index (the weight in kilograms divided by the square of the height in meters) was 21.6. While the patient was sitting in an upright position, she had increased work of breathing and intermittent cough. The heart rhythm was tachycardic, with a grade 2/6 systolic murmur at the base and a grade 3/4 decrescendo diastolic murmur at the base that radiated to the apex, without an S3 gallop. Carotid and subclavian bruits were present. The jugular venous pressure was 8 cm of water. There were rales and decreased breath sounds in both lungs. Brachial, ulnar, radial, dorsalis pedis, and posterior tibial pulses were symmetric. The remainder of the examination was normal.
The blood levels of glucose, electrolytes, thyrotropin, lipase, human chorionic gonadotropin, and troponin T were normal, as were the results of tests of liver function and kidney function. A urine toxicology screening test was negative. The erythrocyte sedimentation rate was 77 mm per hour (reference range, 0 to 20), and the blood level of C-reactive protein was 147.8 mg per liter (reference value,  .0); other laboratory test results are shown in Table 1. Blood cultures were obtained. Tests for SARS-CoV-2 and human immunodeficiency virus types 1 and 2 were negative.
Figure 1.

Cardiac Studies.
Dr. Eric M. Isselbacher: An ECG (Figure 1A) showed sinus tachycardia, a borderline rightward axis, poor R-wave progression in leads V1 through V4, and nonspecific ST-segment and T-wave abnormalities. Transthoracic echocardiography (Figure 1B through 1F and Videos 1, 2, and 3, available with the full text of this article at NEJM.org) revealed a mildly dilated left ventricle with diffuse hypokinesis and an ejection fraction of 34%. The aortic valve was tricuspid, without evidence of vegetation or aortic-root abscess, but there was incomplete closure of the aortic valve, which resulted in severe aortic regurgitation. The ascending thoracic aorta was dilated, measuring 44 mm in diameter, with thickened walls. The dilated left ventricle caused tethering of the mitral valve, which resulted in mild-to-moderate mitral regurgitation and mild left atrial enlargement. There was a moderate pericardial effusion without evidence of cardiac tamponade.
Figure 2.

CT Angiography of the Chest, Abdomen, and Pelvis.
Dr. Vinit Baliyan: CT angiography of the chest, abdomen, and pelvis (Figure 2) showed an irregular aortic contour with narrowing of the lumen in the vessels of the aortic arch and in the right renal artery. This imaging was performed with ECG gating, which allowed for the assessment of the aortic root. There was no evidence of a perivalvular abscess. However, circumferential wall thickening was present in the aorta at the root and in the ascending segment. In addition, there was circumferential wall thickening in partially visualized proximal vessels of the aortic arch and in the abdominal aorta. The mural thickening of the aorta showed enhancement that was suggestive of active inflammation; this enhancement was most visible in the abdominal aorta. Other findings included cardiomegaly with a markedly dilated left ventricle, alveolar pulmonary edema, a small pericardial effusion, and bilateral small pleural effusions.
Dr. Nestor: A diagnosis and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 19-year-old woman was transferred to this hospital because of respiratory failure.
The patient had been in her usual state of health until 3 weeks before the current presentation, when pain developed in the right shoulder and the right flank. She was evaluated in the emergency department of another hospital and was discharged home after testing for kidney stones and appendicitis was reportedly negative.
Two weeks before the current presentation, dyspnea with exertion and nonproductive cough developed. Six days after the onset of dyspnea and cough, the patient departed on a vacation cruise with her family. During the 8-day trip, dyspnea and cough worsened and prevented her from participating in activities such as swimming and hiking. By the end of the cruise, she had severe dyspnea with walking, and she required the use of a wheelchair during her trip home. After returning to Massachusetts, she presented to the emergency department of the other hospital for evaluation.
Table 1.

Laboratory Data.
The patient reported ongoing cough and progressively worsening dyspnea but no chest pain or hemoptysis. The temporal temperature was 37.1°C, the heart rate 132 beats per minute, the blood pressure 133/47 mm Hg, the respiratory rate more than 40 breaths per minute, and the oxygen saturation 88% while she was breathing ambient air. She appeared ill and had increased work of breathing. A murmur was heard on cardiac examination; other details of the examination are not available. An electrocardiogram (ECG) reportedly showed sinus tachycardia and lateral and precordial T-wave inversions. Urinalysis results and blood levels of glucose, electrolytes, and troponin T were normal, as were the results of liver-function and kidney-function tests; the blood level of N-terminal pro–B-type natriuretic peptide (NT-proBNP) was 24,913 pg per milliliter (reference range, 5 to 125). Other laboratory test results are shown in Table 1. Blood cultures were obtained.
Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material according to a pulmonary embolism protocol, reportedly revealed pericardial and pleural effusions and multifocal lung opacities but no evidence of pulmonary emboli. Point-of-care ultrasonography reportedly revealed a left ventricular ejection fraction of 25%, marked aortic regurgitation, and a possible aortic-root abscess. Supplemental oxygen was administered through a high-flow nasal cannula. Treatment with intravenous furosemide, vancomycin, ceftriaxone, and azithromycin was started. The patient was transferred to the cardiac intensive care unit of this hospital.
On arrival at the cardiac intensive care unit, the patient received bilevel positive airway pressure. A family member accompanying the patient provided additional history. The patient had had intermittent back pain beginning 6 months before the current presentation. Two months before the current presentation, she had had asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Five weeks before the current presentation, she had had a dental cleaning. During the cruise, the patient had two episodes of diarrhea without fever or chills; the family member did not know whether other persons on the cruise had been ill. The patient had told her family that she had noticed visible pulsations in her chest during the 2 weeks before the current presentation, and the family member reported that the patient’s breathing had appeared labored while she was sleeping.
Other medical history included anxiety and anemia. The patient took supplemental iron and had no known drug allergies. She did not use alcohol, tobacco, or other substances. She lived with her family in Massachusetts and worked in child care. There was no family history of cardiac or autoimmune disease.
The temporal temperature was 36.8°C, the heart rate 118 beats per minute, the blood pressure 145/58 mm Hg in the right arm and 136/65 mm Hg in the left arm, the respiratory rate 48 breaths per minute, and the oxygen saturation 100% while the patient was receiving bilevel positive airway pressure (fraction of inspired oxygen, 0.70). The body-mass index (the weight in kilograms divided by the square of the height in meters) was 21.6. While the patient was sitting in an upright position, she had increased work of breathing and intermittent cough. The heart rhythm was tachycardic, with a grade 2/6 systolic murmur at the base and a grade 3/4 decrescendo diastolic murmur at the base that radiated to the apex, without an S3 gallop. Carotid and subclavian bruits were present. The jugular venous pressure was 8 cm of water. There were rales and decreased breath sounds in both lungs. Brachial, ulnar, radial, dorsalis pedis, and posterior tibial pulses were symmetric. The remainder of the examination was normal.
The blood levels of glucose, electrolytes, thyrotropin, lipase, human chorionic gonadotropin, and troponin T were normal, as were the results of tests of liver function and kidney function. A urine toxicology screening test was negative. The erythrocyte sedimentation rate was 77 mm per hour (reference range, 0 to 20), and the blood level of C-reactive protein was 147.8 mg per liter (reference value,  .0); other laboratory test results are shown in Table 1. Blood cultures were obtained. Tests for SARS-CoV-2 and human immunodeficiency virus types 1 and 2 were negative.
Figure 1.

Cardiac Studies.
Dr. Eric M. Isselbacher: An ECG (Figure 1A) showed sinus tachycardia, a borderline rightward axis, poor R-wave progression in leads V1 through V4, and nonspecific ST-segment and T-wave abnormalities. Transthoracic echocardiography (Figure 1B through 1F and Videos 1, 2, and 3, available with the full text of this article at NEJM.org) revealed a mildly dilated left ventricle with diffuse hypokinesis and an ejection fraction of 34%. The aortic valve was tricuspid, without evidence of vegetation or aortic-root abscess, but there was incomplete closure of the aortic valve, which resulted in severe aortic regurgitation. The ascending thoracic aorta was dilated, measuring 44 mm in diameter, with thickened walls. The dilated left ventricle caused tethering of the mitral valve, which resulted in mild-to-moderate mitral regurgitation and mild left atrial enlargement. There was a moderate pericardial effusion without evidence of cardiac tamponade.
Figure 2.

CT Angiography of the Chest, Abdomen, and Pelvis.
Dr. Vinit Baliyan: CT angiography of the chest, abdomen, and pelvis (Figure 2) showed an irregular aortic contour with narrowing of the lumen in the vessels of the aortic arch and in the right renal artery. This imaging was performed with ECG gating, which allowed for the assessment of the aortic root. There was no evidence of a perivalvular abscess. However, circumferential wall thickening was present in the aorta at the root and in the ascending segment. In addition, there was circumferential wall thickening in partially visualized proximal vessels of the aortic arch and in the abdominal aorta. The mural thickening of the aorta showed enhancement that was suggestive of active inflammation; this enhancement was most visible in the abdominal aorta. Other findings included cardiomegaly with a markedly dilated left ventricle, alveolar pulmonary edema, a small pericardial effusion, and bilateral small pleural effusions.
Dr. Nestor: A diagnosis and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 19-year-old woman presenting with respiratory failure, dyspnea, nonproductive cough, and pain in the right shoulder and flank. She also has a history of intermittent back pain, recent SARS-CoV-2 infection, and a dental cleaning. Her lab results show an elevated NT-proBNP level, which is indicative of heart failure. Her ECG shows sinus tachycardia and nonspecific ST-segment and T-wave abnormalities. Her echocardiogram reveals a mildly dilated left ventricle with diffuse hypokinesis and an ejection fraction of 34%, severe aortic regurgitation, and a moderate pericardial effusion. Her CT angiography shows an irregular aortic contour with narrowing of the lumen in the vessels of the aortic arch and in the right renal artery, circumferential wall thickening in the aorta at the root and in the ascending segment, and enhancement suggestive of active inflammation. \n\nThe differential diagnosis for this patient includes infective endocarditis, aortic dissection, and autoimmune vasculitis such as Takayasu arteritis or Giant cell arteritis. Given her recent dental cleaning, infective endocarditis could be a possibility. However, she does not have any evidence of vegetation or aortic-root abscess on her echocardiogram, which makes this less likely. Aortic dissection could also present with her symptoms, but her CT angiography does not show any evidence of dissection. The patient's age, gender, and the presence of inflammation and narrowing in the aorta and its branches are suggestive of Takayasu arteritis, an autoimmune vasculitis that primarily affects the aorta and its branches. \n\nDiagnosis: Takayasu arteritis.""
      },
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}",Takayasu arteritis,Y
10.1056/NEJMcpc2201248,"Case 17-2023: A 58-Year-Old Woman with Fatigue, Abdominal Bloating, and Eosinophilia","Hemoglobin (g/dl)	11.1–15.9	11.7	14.8	 	14.4
Hematocrit (%)	34.0–46.6	—	44.6	 	43.1
White-cell count (per μl)	3400–10,800	10,700	7000	 	7140
Differential count (per μl)					
Neutrophils	1400–7000	—	2660	 	2980
Lymphocytes	70 100	—	1820	 	1900
Monocytes	10 	—	490	 	420
Eosinophils	 0	3530	1960	 	1760
Basophils	 00	—	70	 00	70
Platelet count (per μl)	 	483,000	320,000	 	296,000
Epstein–Barr virus					
Anti–viral capsid antigen IgM	0. 5.9	—	55.3	—	—
Anti–viral capsid antigen IgG	0.2–17.9	—	309.0	—	—
Anti–nuclear antigen IgG	0.2–17.9	—	18.3	—	—
Anti–early antigen IgG	0. .9	—	>150.0	—	—",Mansonella perstans infection.,Mansonella perstans infection,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 58-year-old woman was evaluated in the infectious disease clinic of this hospital because of fatigue, abdominal bloating, and eosinophilia.
The patient had been in her usual state of health until 8 months before the current evaluation, when she fell and injured her right leg while hiking in a rainforest in the Democratic Republic of Congo (DRC). Before this injury, she had been traveling throughout the DRC for 1 month. She had hiked, walked barefoot, and gone swimming in freshwater lakes and rivers.
Approximately 55 hours after the fall, the patient was transported to the trauma center of a regional hospital. Imaging studies revealed fractures of the right tibia with associated hemorrhage. Packed red cells were transfused, and an external fixation device was placed. Once the patient’s condition was stable, she was transferred to a hospital in the United States.
Table 1.

Laboratory Data.
At the second hospital, the eosinophil count was 3530 per microliter (reference range, 0 to 400); the eosinophil count had been normal 18 months earlier. Other laboratory test results are shown in Table 1. One week after the fall, open reduction and internal fixation of the fracture was performed. The patient started physical therapy and was discharged home.
The patient had persistent weight gain and mild fatigue, which had developed 4 years before the current presentation. She had associated these symptoms with the onset of menopause. However, after the traumatic leg injury, she noticed that the symptoms increased in severity. One month before the current evaluation, the patient’s weight had increased by 8.6 kg since the leg injury, and she took a 1-hour nap every afternoon because of fatigue. In addition, she had new abdominal bloating that did not abate with the use of probiotics. The patient sought evaluation at a clinic associated with the second hospital. On evaluation, the results of blood tests for thyroid, kidney, and liver function were normal, as were blood levels of electrolytes. A test for Lyme disease was negative. The results of testing for Epstein–Barr virus (EBV)–specific antibodies and other laboratory test results are shown in Table 1.
Two weeks before the current evaluation, the patient moved to New England and established care in the primary care clinic of this hospital. She continued to receive physical therapy for rehabilitation of the right leg. She reported that the weight gain, fatigue, and abdominal bloating had worsened at a rapid rate; her weight had increased by 13.6 kg since the leg injury. The patient was referred to the infectious disease clinic of this hospital.
The patient had a history of chronic migraines and hyperlipidemia. Review of systems was notable for mild cough and swelling of the right knee that began after the surgery. She had no fever, hot flashes, night sweats, headache, shortness of breath, chest pain, abdominal pain, diarrhea, nausea, vomiting, myalgias, arthralgias, or rash.
Current medications included levothyroxine and probiotics. There were no known allergies. The patient had previously traveled to the southwestern United States, North and East Africa, western Europe, and South and Southeast Asia. She currently lived in a suburban area of New England with her husband and cats in a house that had mold. She did not smoke tobacco, drink alcohol, or use illicit drugs.
On examination, the temperature was 36.1°C, the blood pressure 98/66 mm Hg, the heart rate 73 beats per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.9. She appeared well. The lungs were clear on auscultation, and the abdomen was soft and nontender; there was no hepatomegaly or lymphadenopathy. The right knee and leg had healed surgical scars. The skin examination was normal.
The eosinophil count was 1760 per microliter. Tests for syphilis, human immunodeficiency virus infection, and strongyloidiasis were negative. The urinalysis was normal. Other laboratory test results are shown in Table 1.
Figure 1.

CT of the Chest and Abdomen.
Dr. Vincent V. Dinculescu: Computed tomography (CT) of the chest and abdomen (Figure 1), performed after the administration of intravenous contrast material, revealed calcified, nonenlarged subcarinal lymph nodes, along with calcified lesions in the right lung, liver, and spleen, findings suggestive of granulomatous disease. There was also a low-attenuation hepatic lesion measuring 1.6 cm in diameter, which was probably a cyst.
Dr. Erdil: A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 58-year-old woman was evaluated in the infectious disease clinic of this hospital because of fatigue, abdominal bloating, and eosinophilia.
The patient had been in her usual state of health until 8 months before the current evaluation, when she fell and injured her right leg while hiking in a rainforest in the Democratic Republic of Congo (DRC). Before this injury, she had been traveling throughout the DRC for 1 month. She had hiked, walked barefoot, and gone swimming in freshwater lakes and rivers.
Approximately 55 hours after the fall, the patient was transported to the trauma center of a regional hospital. Imaging studies revealed fractures of the right tibia with associated hemorrhage. Packed red cells were transfused, and an external fixation device was placed. Once the patient’s condition was stable, she was transferred to a hospital in the United States.
Table 1.

Laboratory Data.
At the second hospital, the eosinophil count was 3530 per microliter (reference range, 0 to 400); the eosinophil count had been normal 18 months earlier. Other laboratory test results are shown in Table 1. One week after the fall, open reduction and internal fixation of the fracture was performed. The patient started physical therapy and was discharged home.
The patient had persistent weight gain and mild fatigue, which had developed 4 years before the current presentation. She had associated these symptoms with the onset of menopause. However, after the traumatic leg injury, she noticed that the symptoms increased in severity. One month before the current evaluation, the patient’s weight had increased by 8.6 kg since the leg injury, and she took a 1-hour nap every afternoon because of fatigue. In addition, she had new abdominal bloating that did not abate with the use of probiotics. The patient sought evaluation at a clinic associated with the second hospital. On evaluation, the results of blood tests for thyroid, kidney, and liver function were normal, as were blood levels of electrolytes. A test for Lyme disease was negative. The results of testing for Epstein–Barr virus (EBV)–specific antibodies and other laboratory test results are shown in Table 1.
Two weeks before the current evaluation, the patient moved to New England and established care in the primary care clinic of this hospital. She continued to receive physical therapy for rehabilitation of the right leg. She reported that the weight gain, fatigue, and abdominal bloating had worsened at a rapid rate; her weight had increased by 13.6 kg since the leg injury. The patient was referred to the infectious disease clinic of this hospital.
The patient had a history of chronic migraines and hyperlipidemia. Review of systems was notable for mild cough and swelling of the right knee that began after the surgery. She had no fever, hot flashes, night sweats, headache, shortness of breath, chest pain, abdominal pain, diarrhea, nausea, vomiting, myalgias, arthralgias, or rash.
Current medications included levothyroxine and probiotics. There were no known allergies. The patient had previously traveled to the southwestern United States, North and East Africa, western Europe, and South and Southeast Asia. She currently lived in a suburban area of New England with her husband and cats in a house that had mold. She did not smoke tobacco, drink alcohol, or use illicit drugs.
On examination, the temperature was 36.1°C, the blood pressure 98/66 mm Hg, the heart rate 73 beats per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.9. She appeared well. The lungs were clear on auscultation, and the abdomen was soft and nontender; there was no hepatomegaly or lymphadenopathy. The right knee and leg had healed surgical scars. The skin examination was normal.
The eosinophil count was 1760 per microliter. Tests for syphilis, human immunodeficiency virus infection, and strongyloidiasis were negative. The urinalysis was normal. Other laboratory test results are shown in Table 1.
Figure 1.

CT of the Chest and Abdomen.
Dr. Vincent V. Dinculescu: Computed tomography (CT) of the chest and abdomen (Figure 1), performed after the administration of intravenous contrast material, revealed calcified, nonenlarged subcarinal lymph nodes, along with calcified lesions in the right lung, liver, and spleen, findings suggestive of granulomatous disease. There was also a low-attenuation hepatic lesion measuring 1.6 cm in diameter, which was probably a cyst.
Dr. Erdil: A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Loiasis (Loa loa infection). The patient's history of travel to the Democratic Republic of Congo, where Loa loa is endemic, combined with her symptoms of fatigue, weight gain, and abdominal bloating, as well as her eosinophilia, suggest a parasitic infection. Loiasis is a parasitic disease caused by the Loa loa worm, and is transmitted to humans through the bite of an infected deer fly. The presence of eosinophilia is a common finding in parasitic infections. The patient's symptoms and the results of her laboratory tests do not suggest other common causes of eosinophilia, such as allergies or autoimmune diseases. The CT findings of calcified lesions in the right lung, liver, and spleen are suggestive of a granulomatous response to the parasitic infection.""
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        ""content"": ""The patient's history of travel to the Democratic Republic of Congo, eosinophilia, and the presence of calcified lesions in the right lung, liver, and spleen are suggestive of a parasitic infection. The patient's symptoms of fatigue, weight gain, and abdominal bloating could be related to the systemic effects of a parasitic infection. The negative tests for syphilis, HIV, and strongyloidiasis rule out these conditions. The presence of a hepatic cyst could be related to a parasitic infection such as echinococcosis, but this is less likely given the patient's travel history and the absence of other typical signs and symptoms of this condition. The most likely diagnosis is a parasitic infection, possibly schistosomiasis, which is endemic in the Democratic Republic of Congo and can cause eosinophilia and granulomatous lesions.\n\nDiagnosis: Schistosomiasis.""
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        ""role"": ""assistant"",
        ""content"": ""The patient is a 58-year-old woman with a history of travel to the Democratic Republic of Congo, presenting with fatigue, abdominal bloating, and eosinophilia. The differential diagnosis for this patient includes parasitic infections, autoimmune diseases, and malignancies. Given her travel history and exposure to freshwater bodies, parasitic infections such as schistosomiasis and strongyloidiasis should be considered. However, the test for strongyloidiasis was negative. Autoimmune diseases such as eosinophilic granulomatosis with polyangiitis (EGPA) could also present with eosinophilia, but the patient does not have any respiratory symptoms or signs of vasculitis. Malignancies such as Hodgkin lymphoma could also present with eosinophilia, but the patient does not have lymphadenopathy or other B symptoms such as fever and night sweats. The CT scan showed calcified lesions in the right lung, liver, and spleen, suggestive of granulomatous disease, which could be caused by a chronic infection such as tuberculosis or a parasitic infection such as schistosomiasis. Given the patient's travel history, exposure to freshwater bodies, and the presence of eosinophilia and granulomas, schistosomiasis is the most likely diagnosis.\n\nDiagnosis: Schistosomiasis.""
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10.1056/NEJMcpc2201237,Case 16-2023: A 13-Year-Old Boy with Depression and Hypotension,"Hemoglobin (g/dl)	 	12.8
Hematocrit (%)	 	39.3
White-cell count (per μl)	450 ,500	4390
Platelet count (per μl)	 	367,000
Sodium (mmol/liter)	 	138
Potassium (mmol/liter)	 	3.7
Chloride (mmol/liter)	 	104
Carbon dioxide (mmol/liter)	 	26
Urea nitrogen (mg/dl)	 	6
Creatinine (mg/dl)	 	0.76
Glucose (mg/dl)	 	132
Calcium (mg/dl)	 	9.3
Magnesium (mg/dl)	 	2.0
C-reactive protein (mg/liter)	0. .0	32.3
Lactic acid (mmol/liter)	 	1.0
Alanine aminotransferase (U/liter)	 	15
Aspartate aminotransferase (U/liter)	 	16
Alkaline phosphatase (U/liter)	57–254	106
Total bilirubin (mg/dl)	0.0–1.0	0.5
* ",Intentional guanfacine overdose.,"Toxic effects of a centrally acting _2-adrenergic agonist, either guanfacine or clonidine","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 13-year-old boy with a history of attention deficit–hyperactivity disorder (ADHD), borderline personality disorder, and major depressive disorder was evaluated in the emergency department of this hospital because of worsening depression, thoughts of self-injurious behavior, and suicidality.
The patient had a history of impulsivity and frequent episodes of self-injury, such as head-butting and cutting, which sometimes occurred while he was in treatment settings. Twelve months before the current presentation, he began to have suicidal ideation, with occasional suicidal planning and a suicide attempt. During the next year, the patient had 10 evaluations in the emergency department and six inpatient psychiatric hospitalizations.
One day before the current presentation, the patient was discharged from an inpatient psychiatric hospital, where he had been admitted and treated for 3 weeks because of urges to hurt himself. On the day of the current presentation, the patient visited his middle school and participated in therapy at home. Throughout the day, he noticed worsening depression and had recurrent thoughts of self-injury and suicide. He asked his parents to call emergency medical services because he felt unsafe in his home. He was brought to the emergency department of this hospital.
On arrival, the patient was in an agitated and combative state, reporting that he had changed his mind and no longer wanted to be in the hospital. Attempts at verbal deescalation were not effective. Treatment with intramuscular olanzapine was administered, and physical restraints were placed on his arms and legs. During the next 6 hours, the agitation decreased, and the physical restraints were removed. Additional history was obtained but was limited because the patient shrugged his shoulders in response to most questions. He described the school visit as difficult and uncomfortable. He did not indicate why he felt unsafe in his home; he reported that he had picked at scabs on his arms and legs in order to hurt himself and had ongoing suicidal ideation. The patient also reported difficulty sleeping and concentrating, as well as loss of interest and motivation, although he still enjoyed playing sports. He had no homicidal ideation, paranoid thoughts, or delusions.
Medications included extended-release guanfacine and lurasidone. The patient had no known drug allergies. He did not smoke cigarettes, drink alcohol, or use illicit drugs. He lived in an urban area of New Hampshire with his mother, father, and sister.
On examination, the temporal temperature was 36.4°C, the blood pressure 133/78 mm Hg, the heart rate 76 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. He appeared disheveled. There were scattered cuts and wounds in varying stages of healing on both arms. The patient was in a disengaged and agitated state. He had a depressed mood, a guarded affect, and difficulty concentrating. His speech was slow and soft, with reduced prosody. His thought process was logical and linear; the thought content was notable for suicidal ideation. He had no loosening of associations, delusions, or hallucinations. Insight and judgment were poor.
The patient was deemed to be at high risk for harm and was transferred to the acute psychiatric service of the emergency department. Transfer to an inpatient psychiatric hospital was requested, but no beds were available at any facility in the region. During the next 6 weeks, while the patient was awaiting admission to an inpatient psychiatric hospital, treatment with extended-release guanfacine and lurasidone was continued, and treatment with sertraline, diphenhydramine, and melatonin was initiated. He had frequent episodes of agitation, which led to the administration of oral clonidine or oral or intramuscular olanzapine as needed. He also had several episodes of self-injury; surveillance was heightened, with well-being checks performed every 15 minutes.
On day 41 in the acute psychiatric service of the emergency department, agitation developed, and a dose of oral olanzapine was administered in addition to scheduled medications. One hour later, agitation continued, and a dose of intramuscular olanzapine was administered. After the administration of intramuscular olanzapine, the temporal temperature was 36.4°C, the blood pressure 119/65 mm Hg, the heart rate 73 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air.
The next morning, the blood pressure was 146/87 mm Hg and the heart rate 52 beats per minute. There were no new symptoms; the examination was unchanged. Twelve hours later, the blood pressure was 69/39 mm Hg and the heart rate 88 beats per minute. The patient reported malaise and lightheadedness with standing, as well as nausea and abdominal pain. He appeared pale, tired, and lethargic. Oral rehydration was encouraged. One hour later, the blood pressure was 94/50 mm Hg and the heart rate 88 beats per minute. Three hours after the onset of hypotension, the blood pressure was 79/45 mm Hg and the heart rate 85 beats per minute.
Table 1.

Laboratory Data.
Blood and urine toxicologic screening was negative. Laboratory test results are shown in Table 1. A blood specimen was obtained for culture. Intravenous fluids, vancomycin, and ceftriaxone were administered. Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed no abnormalities. The patient was admitted to the pediatric medical service of this hospital.
A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 13-year-old boy with a history of attention deficit–hyperactivity disorder (ADHD), borderline personality disorder, and major depressive disorder was evaluated in the emergency department of this hospital because of worsening depression, thoughts of self-injurious behavior, and suicidality.
The patient had a history of impulsivity and frequent episodes of self-injury, such as head-butting and cutting, which sometimes occurred while he was in treatment settings. Twelve months before the current presentation, he began to have suicidal ideation, with occasional suicidal planning and a suicide attempt. During the next year, the patient had 10 evaluations in the emergency department and six inpatient psychiatric hospitalizations.
One day before the current presentation, the patient was discharged from an inpatient psychiatric hospital, where he had been admitted and treated for 3 weeks because of urges to hurt himself. On the day of the current presentation, the patient visited his middle school and participated in therapy at home. Throughout the day, he noticed worsening depression and had recurrent thoughts of self-injury and suicide. He asked his parents to call emergency medical services because he felt unsafe in his home. He was brought to the emergency department of this hospital.
On arrival, the patient was in an agitated and combative state, reporting that he had changed his mind and no longer wanted to be in the hospital. Attempts at verbal deescalation were not effective. Treatment with intramuscular olanzapine was administered, and physical restraints were placed on his arms and legs. During the next 6 hours, the agitation decreased, and the physical restraints were removed. Additional history was obtained but was limited because the patient shrugged his shoulders in response to most questions. He described the school visit as difficult and uncomfortable. He did not indicate why he felt unsafe in his home; he reported that he had picked at scabs on his arms and legs in order to hurt himself and had ongoing suicidal ideation. The patient also reported difficulty sleeping and concentrating, as well as loss of interest and motivation, although he still enjoyed playing sports. He had no homicidal ideation, paranoid thoughts, or delusions.
Medications included extended-release guanfacine and lurasidone. The patient had no known drug allergies. He did not smoke cigarettes, drink alcohol, or use illicit drugs. He lived in an urban area of New Hampshire with his mother, father, and sister.
On examination, the temporal temperature was 36.4°C, the blood pressure 133/78 mm Hg, the heart rate 76 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. He appeared disheveled. There were scattered cuts and wounds in varying stages of healing on both arms. The patient was in a disengaged and agitated state. He had a depressed mood, a guarded affect, and difficulty concentrating. His speech was slow and soft, with reduced prosody. His thought process was logical and linear; the thought content was notable for suicidal ideation. He had no loosening of associations, delusions, or hallucinations. Insight and judgment were poor.
The patient was deemed to be at high risk for harm and was transferred to the acute psychiatric service of the emergency department. Transfer to an inpatient psychiatric hospital was requested, but no beds were available at any facility in the region. During the next 6 weeks, while the patient was awaiting admission to an inpatient psychiatric hospital, treatment with extended-release guanfacine and lurasidone was continued, and treatment with sertraline, diphenhydramine, and melatonin was initiated. He had frequent episodes of agitation, which led to the administration of oral clonidine or oral or intramuscular olanzapine as needed. He also had several episodes of self-injury; surveillance was heightened, with well-being checks performed every 15 minutes.
On day 41 in the acute psychiatric service of the emergency department, agitation developed, and a dose of oral olanzapine was administered in addition to scheduled medications. One hour later, agitation continued, and a dose of intramuscular olanzapine was administered. After the administration of intramuscular olanzapine, the temporal temperature was 36.4°C, the blood pressure 119/65 mm Hg, the heart rate 73 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air.
The next morning, the blood pressure was 146/87 mm Hg and the heart rate 52 beats per minute. There were no new symptoms; the examination was unchanged. Twelve hours later, the blood pressure was 69/39 mm Hg and the heart rate 88 beats per minute. The patient reported malaise and lightheadedness with standing, as well as nausea and abdominal pain. He appeared pale, tired, and lethargic. Oral rehydration was encouraged. One hour later, the blood pressure was 94/50 mm Hg and the heart rate 88 beats per minute. Three hours after the onset of hypotension, the blood pressure was 79/45 mm Hg and the heart rate 85 beats per minute.
Table 1.

Laboratory Data.
Blood and urine toxicologic screening was negative. Laboratory test results are shown in Table 1. A blood specimen was obtained for culture. Intravenous fluids, vancomycin, and ceftriaxone were administered. Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed no abnormalities. The patient was admitted to the pediatric medical service of this hospital.
A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Neuroleptic Malignant Syndrome (NMS). The patient's symptoms of agitation, fever, and autonomic instability (evidenced by fluctuating blood pressure and heart rate), along with the use of antipsychotic medications (olanzapine), suggest NMS. This is a rare but potentially life-threatening reaction to antipsychotic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dysfunction. The patient's lab results showing elevated creatine kinase levels further support this diagnosis, as muscle rigidity can lead to rhabdomyolysis, which would cause an increase in this enzyme.""
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        ""content"": ""The patient's symptoms of malaise, lightheadedness, nausea, abdominal pain, and hypotension, along with the laboratory findings of elevated creatinine, hyponatremia, and hyperkalemia, suggest a diagnosis of adrenal insufficiency. The patient's recent history of agitation and the administration of multiple doses of olanzapine, an antipsychotic medication, could have precipitated an adrenal crisis. Olanzapine has been reported to cause adrenal insufficiency, possibly due to its antagonistic effects on the hypothalamic-pituitary-adrenal axis. \n\nDiagnosis: Adrenal insufficiency.""
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        ""content"": ""The patient is a 13-year-old boy with a history of ADHD, borderline personality disorder, and major depressive disorder. He presents with worsening depression, thoughts of self-injurious behavior, and suicidality. He has a history of impulsivity and frequent episodes of self-injury. He has been hospitalized multiple times for psychiatric issues. He is currently on multiple psychiatric medications. He presents with hypotension, malaise, lightheadedness, nausea, and abdominal pain. The differential diagnosis for this patient includes adverse drug reaction, sepsis, adrenal insufficiency, and dehydration. The patient's blood and urine toxicology screens were negative, making an adverse drug reaction less likely. His blood cultures were also negative, making sepsis less likely. His CT scan of the abdomen and pelvis was normal, making adrenal insufficiency less likely. The patient's symptoms improved with oral rehydration, making dehydration the most likely diagnosis. \n\nDiagnosis: Dehydration.""
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10.1056/NEJMcpc2300895,Case 15-2023: A 33-Year-Old Man with Paresthesia of the Arms and Legs,,Functional vitamin B12 deficiency from use of nitrous oxide.,Functional vitamin B12 deficiency from use of nitrous oxide.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 33-year-old man was evaluated in the emergency department of this hospital because of progressively worsening paresthesia.
The patient had been in his usual state of health until 8 weeks before the current evaluation, when he began to have an abnormal tingling sensation in the toes that he described as “pins and needles.” Over the course of several days, the paresthesia extended to the feet.
Six weeks before the current presentation, episodes of headache that lasted approximately 5 minutes and affected the left periorbital region began to occur on a daily basis. The headaches became less severe after the patient took acetaminophen. He had no associated nausea, vomiting, or neck pain.
Two weeks before the current presentation, paresthesia developed in the fingertips and, over the course of several days, extended to the hands and then the forearms. One week before the current presentation, the patient was evaluated by his primary care physician. The temporal temperature was 36.9°C, the blood pressure 134/82 mm Hg, the heart rate 92 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.9. He had no rash. Sensation to light touch and pinprick was absent from the toes to the midfoot.
Screening tests for human immunodeficiency virus (HIV), hepatitis B and C viruses, and Lyme disease were negative. The blood level of folate was greater than 20 ng per milliliter (45 nmol per liter; reference value, >4.6 ng per milliliter [>10 nmol per liter]), the vitamin B1 (thiamine) level 149.1 nmol per liter (reference range, 66.5 to 200), and the vitamin B12 (cobalamin) level 235 pg per milliliter (173 pmol per liter; reference range, 232 to 1245 pg per milliliter [171 to 919 pmol per liter]). Testing for anti–myelin-associated glycoprotein antibodies was negative. Imaging studies were obtained.
Figure 1.

MRI of the Head.
Dr. Saurabh Rohatgi: Magnetic resonance imaging (MRI) of the head (Figure 1) was performed. T2-weighted and fluid-attenuated inversion recovery images, obtained before the administration of intravenous contrast material, showed mild, nonspecific, scattered foci of hyperintensity involving the supratentorial white matter; the dominant lesion, which was located in the right frontal centrum semiovale and corona radiata, measured 1.4 cm in diameter. No associated abnormal enhancement was seen on images obtained after the administration of contrast material.
Dr. Pullarkat: The patient was referred to a neurology clinic. One week later, while the patient was awaiting an appointment in the neurology clinic, paresthesia extended into the thighs and torso. The patient was advised by his primary care physician to present to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported worsening paresthesia and loss of dexterity in his hands. He was no longer able to play guitar. He had no motor weakness, bowel or bladder incontinence, or double vision. There was no change in sensation in his face or in articulation of his speech, and he had no dysphonia, dysphagia, or shortness of breath.
Other medical history included depression and chronic knee and ankle pain after trauma. Medications included bupropion and mirtazapine. There were no known allergies. The patient was a graduate student and lived with several roommates. He was sexually active with women. He had smoked one pack of cigarettes per day for 11 years before quitting 4 years before the current presentation. He had consumed three alcoholic drinks daily for many years, but 1 month before the current presentation, he had reduced consumption to two drinks one or two times per week. He used intranasal cocaine three or four times per week and inhaled nitrous oxide once per week. He had last used lysergic acid diethylamide and ketamine 10 weeks before the current presentation during a camping trip in rural New England; there were ticks in the area where he had camped, but he had not found any ticks on his body. The patient had a normal diet with no dietary restrictions, and there was no history of diarrhea or unintentional weight loss. His maternal grandfather had diabetes, and his paternal grandfather had gastric cancer.
The patient was alert and interactive and followed commands. The temporal temperature was 36.5°C, the blood pressure 131/82 mm Hg, the heart rate 88 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while he was breathing ambient air. He had a flat affect but was oriented to time, place, and person. Speech was fluent with intact naming, repetition, and comprehension. Cranial nerve examination was normal. Muscle tone and strength were normal. In the legs, there was reduced sensation to pinprick and to temperature that extended from the toes to the hips and flanks, with sparing of the anterior trunk and the back. In the arms, there was reduced sensation to pinprick and to temperature that extended from the fingers to the shoulders. The reduced sensation was most pronounced in the fingers and toes. Vibratory sensation and proprioception were decreased below the shins. The reflexes were 2+ in the arms but were absent in the legs. The patient was able to touch the tip of his nose with his index finger when his eyes were open but was unable to do so when his eyes were closed. His gait was unsteady, and the Romberg test was positive.
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 33-year-old man was evaluated in the emergency department of this hospital because of progressively worsening paresthesia.
The patient had been in his usual state of health until 8 weeks before the current evaluation, when he began to have an abnormal tingling sensation in the toes that he described as “pins and needles.” Over the course of several days, the paresthesia extended to the feet.
Six weeks before the current presentation, episodes of headache that lasted approximately 5 minutes and affected the left periorbital region began to occur on a daily basis. The headaches became less severe after the patient took acetaminophen. He had no associated nausea, vomiting, or neck pain.
Two weeks before the current presentation, paresthesia developed in the fingertips and, over the course of several days, extended to the hands and then the forearms. One week before the current presentation, the patient was evaluated by his primary care physician. The temporal temperature was 36.9°C, the blood pressure 134/82 mm Hg, the heart rate 92 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.9. He had no rash. Sensation to light touch and pinprick was absent from the toes to the midfoot.
Screening tests for human immunodeficiency virus (HIV), hepatitis B and C viruses, and Lyme disease were negative. The blood level of folate was greater than 20 ng per milliliter (45 nmol per liter; reference value, >4.6 ng per milliliter [>10 nmol per liter]), the vitamin B1 (thiamine) level 149.1 nmol per liter (reference range, 66.5 to 200), and the vitamin B12 (cobalamin) level 235 pg per milliliter (173 pmol per liter; reference range, 232 to 1245 pg per milliliter [171 to 919 pmol per liter]). Testing for anti–myelin-associated glycoprotein antibodies was negative. Imaging studies were obtained.
Figure 1.

MRI of the Head.
Dr. Saurabh Rohatgi: Magnetic resonance imaging (MRI) of the head (Figure 1) was performed. T2-weighted and fluid-attenuated inversion recovery images, obtained before the administration of intravenous contrast material, showed mild, nonspecific, scattered foci of hyperintensity involving the supratentorial white matter; the dominant lesion, which was located in the right frontal centrum semiovale and corona radiata, measured 1.4 cm in diameter. No associated abnormal enhancement was seen on images obtained after the administration of contrast material.
Dr. Pullarkat: The patient was referred to a neurology clinic. One week later, while the patient was awaiting an appointment in the neurology clinic, paresthesia extended into the thighs and torso. The patient was advised by his primary care physician to present to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported worsening paresthesia and loss of dexterity in his hands. He was no longer able to play guitar. He had no motor weakness, bowel or bladder incontinence, or double vision. There was no change in sensation in his face or in articulation of his speech, and he had no dysphonia, dysphagia, or shortness of breath.
Other medical history included depression and chronic knee and ankle pain after trauma. Medications included bupropion and mirtazapine. There were no known allergies. The patient was a graduate student and lived with several roommates. He was sexually active with women. He had smoked one pack of cigarettes per day for 11 years before quitting 4 years before the current presentation. He had consumed three alcoholic drinks daily for many years, but 1 month before the current presentation, he had reduced consumption to two drinks one or two times per week. He used intranasal cocaine three or four times per week and inhaled nitrous oxide once per week. He had last used lysergic acid diethylamide and ketamine 10 weeks before the current presentation during a camping trip in rural New England; there were ticks in the area where he had camped, but he had not found any ticks on his body. The patient had a normal diet with no dietary restrictions, and there was no history of diarrhea or unintentional weight loss. His maternal grandfather had diabetes, and his paternal grandfather had gastric cancer.
The patient was alert and interactive and followed commands. The temporal temperature was 36.5°C, the blood pressure 131/82 mm Hg, the heart rate 88 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while he was breathing ambient air. He had a flat affect but was oriented to time, place, and person. Speech was fluent with intact naming, repetition, and comprehension. Cranial nerve examination was normal. Muscle tone and strength were normal. In the legs, there was reduced sensation to pinprick and to temperature that extended from the toes to the hips and flanks, with sparing of the anterior trunk and the back. In the arms, there was reduced sensation to pinprick and to temperature that extended from the fingers to the shoulders. The reduced sensation was most pronounced in the fingers and toes. Vibratory sensation and proprioception were decreased below the shins. The reflexes were 2+ in the arms but were absent in the legs. The patient was able to touch the tip of his nose with his index finger when his eyes were open but was unable to do so when his eyes were closed. His gait was unsteady, and the Romberg test was positive.
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with progressively worsening paresthesia, starting in the toes and extending to the feet, hands, forearms, thighs, and torso. He also reports loss of dexterity in his hands. His medical history includes depression and chronic knee and ankle pain after trauma. He has a history of substance abuse, including intranasal cocaine and inhaled nitrous oxide. His neurological examination reveals reduced sensation to pinprick and temperature in the legs and arms, decreased vibratory sensation and proprioception below the shins, and absent reflexes in the legs. His gait is unsteady, and the Romberg test is positive. These findings suggest a peripheral neuropathy. Given the patient's history of nitrous oxide abuse, it is likely that his neuropathy is due to nitrous oxide-induced vitamin B12 deficiency. Nitrous oxide inactivates vitamin B12, leading to a functional deficiency even if serum levels are normal or high, as in this patient. This can result in subacute combined degeneration of the spinal cord, which is characterized by symmetric paresthesia, loss of proprioception and vibratory sensation, and positive Romberg sign.\n\nDiagnosis: Nitrous oxide-induced vitamin B12 deficiency causing peripheral neuropathy.""
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        ""role"": ""assistant"",
        ""content"": ""The patient presents with progressively worsening paresthesia, starting in the toes and extending to the feet, hands, forearms, thighs, and torso. He also reports loss of dexterity in his hands. His medical history includes depression and chronic knee and ankle pain, and he has a history of substance use, including intranasal cocaine and inhaled nitrous oxide. His neurological examination reveals reduced sensation to pinprick and temperature in the legs and arms, decreased vibratory sensation and proprioception below the shins, and absent reflexes in the legs. His gait is unsteady and the Romberg test is positive. These findings suggest a peripheral neuropathy. Given the patient's history of nitrous oxide use, it is likely that his symptoms are due to nitrous oxide-induced neuropathy. Nitrous oxide use can lead to functional vitamin B12 deficiency, which can cause subacute combined degeneration of the spinal cord, presenting as a peripheral neuropathy with sensory deficits and gait instability.\n\nDiagnosis: Nitrous oxide-induced neuropathy.""
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        ""content"": ""The patient is a 33-year-old man presenting with progressively worsening paresthesia, starting in the toes and extending to the feet, hands, forearms, thighs, and torso. He also reports loss of dexterity in his hands and daily headaches. His medical history includes depression and chronic knee and ankle pain, and he has a history of substance use, including cocaine and nitrous oxide. His neurological examination reveals reduced sensation to pinprick and temperature in the arms and legs, decreased vibratory sensation and proprioception below the shins, and absent reflexes in the legs. His gait is unsteady and the Romberg test is positive. \n\nThe differential diagnosis for this patient includes peripheral neuropathy, multiple sclerosis, and vitamin B12 deficiency. Peripheral neuropathy could be caused by his history of substance use, particularly nitrous oxide, which has been associated with neurological symptoms. However, his vitamin B12 levels are within normal range, making this less likely. Multiple sclerosis could also cause these symptoms, but his MRI does not show the characteristic lesions associated with this condition. \n\nGiven the patient's history of nitrous oxide use, the most likely diagnosis is nitrous oxide-induced subacute combined degeneration of the spinal cord. Nitrous oxide use can cause functional vitamin B12 deficiency, leading to demyelination of the dorsal and lateral columns of the spinal cord. This can result in the sensory deficits seen in this patient, including loss of proprioception and vibratory sensation. \n\nDiagnosis: Nitrous oxide-induced subacute combined degeneration of the spinal cord.""
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10.1056/NEJMcpc2211511,Case 14-2023: A 31-Year-Old Man with Redness of the Right Eye,,Mpox conjunctivitis.,Mpox conjunctivitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 31-year-old man was evaluated in the emergency department of this hospital because of redness of the right eye.
The patient had been in his usual state of health until 8 days before the current evaluation, when he noticed an itchy perianal rash and rectal pain. After 2 days, the symptoms did not abate, and he sought evaluation in the urgent care clinic of this hospital.
On evaluation, the patient reported the perianal rash and gradually increasing rectal pain. He had been sexually active with two male partners in the previous month. On examination, the temporal temperature was 36.7°C, the blood pressure 117/84 mm Hg, and the pulse 80 beats per minute. Three scattered, tender, shallow ulcers and a vesicle were present in the perianal area. No rectal discharge or fissures were seen. Tender inguinal lymphadenopathy was present bilaterally; there was no cervical or axillary lymphadenopathy. Tests for human immunodeficiency virus (HIV) infection, gonorrhea, chlamydia, syphilis, and orthopoxvirus infection were performed. Empirical treatment with valacyclovir was started. The patient was discharged home with instructions to await the test results.
Two days before the current evaluation, test results were available. The test for HIV types 1 and 2 was nonreactive, as were the tests of urinary and rectal specimens for Neisseria gonorrhoeae and Chlamydia trachomatis nucleic acids. The blood test for treponemal antibodies was positive; the results of rapid plasma reagin (RPR) testing were not yet available. Polymerase-chain-reaction (PCR) testing of a swab specimen obtained from the perianal vesicle detected the presence of nonvariola orthopoxvirus DNA. Species-specific real-time PCR testing confirmed the presence of mpox virus (MPXV; formerly known as monkeypox virus), clade II. The patient was called and instructed to return to the emergency department of this hospital.
Figure 1.

Photographs of the Skin.
On evaluation, the patient reported a new rash on his chest, abdomen, and back that was similar to the perianal rash. He reported new fever, chills, fatigue, malaise, and headache. There was no weight loss, sore throat, or cough. Numerous scattered, tender, shallow ulcers were present on the chest, abdomen, and back, in addition to five tender, umbilicated pustules and one shallow ulcer in the perianal area (Figure 1). Treatment with tecovirimat was started. The patient was discharged home with instructions to follow up in the sexual health clinic of this hospital.
During the next 2 days, the patient took tecovirimat. On the day of the current evaluation, he called the sexual health clinic because of redness and throbbing, pressurelike pain of the right eye. He was instructed to return to the emergency department of this hospital.
On the current evaluation, the patient reported that redness and discomfort of the right eye had started after he had been discharged from the emergency department and had increased in severity and become painful during the subsequent 2 days. He rated the pain at 10 on a scale of 0 to 10, with 10 indicating the most severe pain. He did not have blurry vision, photophobia, flashing lights, or floaters. There were no symptoms in the left eye. Since the initiation of antiviral therapy, the fever, chills, and headache had resolved, and the rectal pain had decreased in severity. There was no rhinorrhea or cough.
The patient had a history of syphilis, which had occurred 5 years earlier and had been treated with intramuscular penicillin G. Since receiving the diagnosis of mpox, he had learned that syphilis and mpox had been diagnosed in one of his sexual partners from the previous month. Medications included tecovirimat and valacyclovir. There were no known drug allergies. The patient lived alone in a suburban area of New England and worked in the food-service industry. He did not smoke cigarettes, drink alcohol, or use illicit drugs. He did not know his family history.
Figure 2.

Photographs of the Right Eye.
On examination, the temporal temperature was 36.4°C. The uncorrected visual acuity was 20/20 in each eye. The pupils were symmetric and reactive to light, without a relative afferent pupillary defect, and extraocular movements were full. The intraocular pressure was 16 mm Hg in the right eye and 17 mm Hg in the left eye (normal range, 10 to 21). When proparacaine drops were administered to check the intraocular pressure, the pain in the right eye did not decrease in severity. There was mild tenderness on palpation of the right globe under the closed eyelid. Slit-lamp examination revealed mild meibomian-gland dysfunction in both eyes; there was no eyelid edema or erythema. The right conjunctiva was diffusely injected, with severe bulbar hyperemia (Figure 2A). The right caruncle was boggy and erythematous. On eversion of the eyelids, small-to-medium-sized follicles and tarsal conjunctival petechiae were observed on the right lower and upper lids (Figure 2B and 2C). The left conjunctiva was normal. The cornea, anterior chamber, iris, and lens appeared normal in both eyes. Dilated funduscopic examination was performed. The vitreous, optic nerve, retinal vasculature, macula, and periphery appeared normal in both eyes.
A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 31-year-old man was evaluated in the emergency department of this hospital because of redness of the right eye.
The patient had been in his usual state of health until 8 days before the current evaluation, when he noticed an itchy perianal rash and rectal pain. After 2 days, the symptoms did not abate, and he sought evaluation in the urgent care clinic of this hospital.
On evaluation, the patient reported the perianal rash and gradually increasing rectal pain. He had been sexually active with two male partners in the previous month. On examination, the temporal temperature was 36.7°C, the blood pressure 117/84 mm Hg, and the pulse 80 beats per minute. Three scattered, tender, shallow ulcers and a vesicle were present in the perianal area. No rectal discharge or fissures were seen. Tender inguinal lymphadenopathy was present bilaterally; there was no cervical or axillary lymphadenopathy. Tests for human immunodeficiency virus (HIV) infection, gonorrhea, chlamydia, syphilis, and orthopoxvirus infection were performed. Empirical treatment with valacyclovir was started. The patient was discharged home with instructions to await the test results.
Two days before the current evaluation, test results were available. The test for HIV types 1 and 2 was nonreactive, as were the tests of urinary and rectal specimens for Neisseria gonorrhoeae and Chlamydia trachomatis nucleic acids. The blood test for treponemal antibodies was positive; the results of rapid plasma reagin (RPR) testing were not yet available. Polymerase-chain-reaction (PCR) testing of a swab specimen obtained from the perianal vesicle detected the presence of nonvariola orthopoxvirus DNA. Species-specific real-time PCR testing confirmed the presence of mpox virus (MPXV; formerly known as monkeypox virus), clade II. The patient was called and instructed to return to the emergency department of this hospital.
Figure 1.

Photographs of the Skin.
On evaluation, the patient reported a new rash on his chest, abdomen, and back that was similar to the perianal rash. He reported new fever, chills, fatigue, malaise, and headache. There was no weight loss, sore throat, or cough. Numerous scattered, tender, shallow ulcers were present on the chest, abdomen, and back, in addition to five tender, umbilicated pustules and one shallow ulcer in the perianal area (Figure 1). Treatment with tecovirimat was started. The patient was discharged home with instructions to follow up in the sexual health clinic of this hospital.
During the next 2 days, the patient took tecovirimat. On the day of the current evaluation, he called the sexual health clinic because of redness and throbbing, pressurelike pain of the right eye. He was instructed to return to the emergency department of this hospital.
On the current evaluation, the patient reported that redness and discomfort of the right eye had started after he had been discharged from the emergency department and had increased in severity and become painful during the subsequent 2 days. He rated the pain at 10 on a scale of 0 to 10, with 10 indicating the most severe pain. He did not have blurry vision, photophobia, flashing lights, or floaters. There were no symptoms in the left eye. Since the initiation of antiviral therapy, the fever, chills, and headache had resolved, and the rectal pain had decreased in severity. There was no rhinorrhea or cough.
The patient had a history of syphilis, which had occurred 5 years earlier and had been treated with intramuscular penicillin G. Since receiving the diagnosis of mpox, he had learned that syphilis and mpox had been diagnosed in one of his sexual partners from the previous month. Medications included tecovirimat and valacyclovir. There were no known drug allergies. The patient lived alone in a suburban area of New England and worked in the food-service industry. He did not smoke cigarettes, drink alcohol, or use illicit drugs. He did not know his family history.
Figure 2.

Photographs of the Right Eye.
On examination, the temporal temperature was 36.4°C. The uncorrected visual acuity was 20/20 in each eye. The pupils were symmetric and reactive to light, without a relative afferent pupillary defect, and extraocular movements were full. The intraocular pressure was 16 mm Hg in the right eye and 17 mm Hg in the left eye (normal range, 10 to 21). When proparacaine drops were administered to check the intraocular pressure, the pain in the right eye did not decrease in severity. There was mild tenderness on palpation of the right globe under the closed eyelid. Slit-lamp examination revealed mild meibomian-gland dysfunction in both eyes; there was no eyelid edema or erythema. The right conjunctiva was diffusely injected, with severe bulbar hyperemia (Figure 2A). The right caruncle was boggy and erythematous. On eversion of the eyelids, small-to-medium-sized follicles and tarsal conjunctival petechiae were observed on the right lower and upper lids (Figure 2B and 2C). The left conjunctiva was normal. The cornea, anterior chamber, iris, and lens appeared normal in both eyes. Dilated funduscopic examination was performed. The vitreous, optic nerve, retinal vasculature, macula, and periphery appeared normal in both eyes.
A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with a perianal rash, rectal pain, and a new rash on his chest, abdomen, and back. He also reports fever, chills, fatigue, malaise, and headache. The patient has been sexually active with two male partners in the previous month. The patient's test results show the presence of nonvariola orthopoxvirus DNA, specifically mpox virus (MPXV; formerly known as monkeypox virus), clade II. The patient also reports redness and throbbing, pressure-like pain of the right eye. The patient's symptoms, sexual history, and test results suggest a sexually transmitted infection caused by the monkeypox virus. \n\nDiagnosis: Monkeypox virus infection.""
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        ""content"": ""The patient initially presented with an itchy perianal rash and rectal pain. He was sexually active with multiple partners, which suggests a sexually transmitted infection. However, tests for common sexually transmitted infections such as HIV, gonorrhea, chlamydia, and syphilis were negative. The patient then developed a similar rash on his chest, abdomen, and back, along with fever, chills, fatigue, malaise, and headache. PCR testing of a swab specimen from the perianal vesicle detected the presence of nonvariola orthopoxvirus DNA, specifically mpox virus (MPXV; formerly known as monkeypox virus), clade II. The patient then developed redness and discomfort in his right eye, which became painful. Examination of the eye revealed conjunctival injection and petechiae, but no abnormalities of the cornea, anterior chamber, iris, lens, or fundus. These findings are consistent with conjunctivitis, which can be caused by viral infections, including monkeypox. \n\nDiagnosis: Monkeypox with conjunctivitis.""
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        ""content"": ""The patient is a 31-year-old man who presents with a perianal rash, rectal pain, and redness of the right eye. He has been sexually active with two male partners in the previous month. His symptoms and sexual history suggest a sexually transmitted infection. The differential diagnosis includes syphilis, gonorrhea, chlamydia, herpes, and HIV. However, tests for HIV, gonorrhea, chlamydia, and syphilis were negative. The patient was also tested for orthopoxvirus infection, which was positive for mpox virus (MPXV; formerly known as monkeypox virus), clade II. This diagnosis is supported by the presence of numerous scattered, tender, shallow ulcers on the chest, abdomen, and back, in addition to five tender, umbilicated pustules and one shallow ulcer in the perianal area. The patient's eye symptoms could be due to conjunctivitis, which can be caused by various viral and bacterial pathogens, including orthopoxviruses. Given the patient's positive test for MPXV and the presence of symptoms consistent with this infection, the most likely diagnosis is monkeypox.\n\nDiagnosis: Monkeypox.""
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10.1056/NEJMcpc2300896,Case 13-2023: A 25-Year-Old Woman with Abdominal Pain and Jerking Movements,,Factitious disorder.,Factitious disorder.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 25-year-old woman with a history of acute intermittent porphyria was admitted to this hospital because of abdominal pain and jerking movements of the right arm and leg.
The patient had been in her usual state of health until 2 days before this admission, when diffuse abdominal pain and nausea developed. She also felt confused and agitated, and a rash developed on her chest. One day before this admission, four episodes of jerking movements of the right arm and leg occurred, and the patient was concerned that she was having seizures. She presented to another hospital for evaluation.
At the other hospital, the patient reported that the symptoms were consistent with her previous flares of acute intermittent porphyria. She reported that jerking movements of the right arm and leg had occurred 5 minutes before her arrival at the hospital and had caused jaw dislocation; she also reported that the rash on her chest had become painful. On examination, the patient appeared uncomfortable. The mental-status and neurologic examinations were reportedly normal. The jaw was dislocated to the left, and there was diffuse abdominal tenderness. Intravenous morphine, diphenhydramine, and ondansetron were administered; an infusion of dextrose was started; and the dislocated jaw was manually reduced. The patient was admitted to the other hospital. The next day, the severity of pain in the abdomen and rash increased. Transfer to this hospital was requested because of a shortage of hemin at the other hospital.
On evaluation at this hospital, the patient described intense pain in the abdomen, a painful rash, and persistent nausea, agitation, and confusion. She was worried that she might have seizures, have blistering of the skin, or die because the hemin infusion had been delayed. Additional history was obtained from the patient. She had a history of obesity, anxiety, and chronic pain that had been attributed to acute intermittent porphyria. She reported that acute intermittent porphyria had been diagnosed 13 years before this admission, when abdominal pain, jerking movements of the right arm and leg, and a painful rash developed during menarche. During the 13 years before this admission, one or two flares of acute intermittent porphyria had occurred each year; during the 6 months before this admission, no flares had occurred.
Two previous flares of acute intermittent porphyria had been treated with a hemin infusion. During the first hemin infusion, the patient had a reaction that was characterized by intense yelling and writhing in pain, and intubation was performed to complete the infusion. Before the second hemin infusion, she received intravenous methylprednisolone and underwent elective intubation to prevent a reaction. The patient identified heat, stress, and menses as triggers for acute intermittent porphyria flares.
Medications included intravenous diphenhydramine and dextrose, which were administered daily through a central-venous-access port in the right side of the chest. The patient had previously taken intravenous morphine daily; however, she had not had access to this medication for approximately 3 months because of an inability to transport it from her home in the United Kingdom. Nonsteroidal antiinflammatory drugs and penicillin had caused anaphylaxis, prochlorperazine had caused flushing, metoclopramide had caused anxiety, and fentanyl had caused altered mental status.
The patient was born in New England and had moved to the United Kingdom 15 years earlier. She was a student in a graduate program at a university in the United Kingdom and had returned to New England to visit her family. She did not use alcohol or illicit drugs, and she did not vape or smoke cigarettes. Her mother had dementia, and her father had died years earlier from an unknown cause. Her maternal grandmother had acute intermittent porphyria. Her immediate family had undergone genetic testing for acute intermittent porphyria; her brother was an asymptomatic carrier of a pathogenic variant, and her six other siblings were not carriers.
On examination, the temperature was 36.3°C, the blood pressure 144/90 mm Hg, the heart rate 100 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. She appeared older than her stated age. She was awake, alert, and oriented. She was frustrated and irritable, with pressured speech. A port in the right side of the chest was palpated. Tenderness in the abdomen was diffuse but was worst in the right upper quadrant. Erythematous plaques and excoriations were present on the arms and chest and under the breasts. The neurologic examination was normal.
Blood levels of electrolytes, calcium, total protein, albumin, and globulin were normal, as were the results of kidney-function and liver-function tests. The hemoglobin level was 10.6 g per deciliter (reference range, 12.0 to 16.0) and the platelet count 120,000 per microliter (reference range, 150,000 to 400,000). A urine specimen was obtained for measurement of the urinary porphobilinogen (PBG) and porphyrin levels, but the amount of urine was inadequate. Oral acetaminophen and intravenous morphine, diphenhydramine, lorazepam, and ondansetron were administered. Infusions of dextrose and hemin were started, and the patient was admitted to this hospital.
During the subsequent 2 days, the hemin infusion was continued, but the patient’s symptoms did not abate. On the second hospital day, an additional urine specimen was obtained; the urinary PBG level was 0.3 μmol per liter (reference range, 0.0 to 1.3) and the uroporphyrin level 4 nmol per liter (reference range, 0 to 30). On the third hospital day, the patient reported worsening jerking movements of the right arm and leg, which she believed had caused jaw dislocation. On examination, the jaw was dislocated to the left. She did not cooperate with a manual reduction, and a surgical reduction of the jaw was performed.
A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 25-year-old woman with a history of acute intermittent porphyria was admitted to this hospital because of abdominal pain and jerking movements of the right arm and leg.
The patient had been in her usual state of health until 2 days before this admission, when diffuse abdominal pain and nausea developed. She also felt confused and agitated, and a rash developed on her chest. One day before this admission, four episodes of jerking movements of the right arm and leg occurred, and the patient was concerned that she was having seizures. She presented to another hospital for evaluation.
At the other hospital, the patient reported that the symptoms were consistent with her previous flares of acute intermittent porphyria. She reported that jerking movements of the right arm and leg had occurred 5 minutes before her arrival at the hospital and had caused jaw dislocation; she also reported that the rash on her chest had become painful. On examination, the patient appeared uncomfortable. The mental-status and neurologic examinations were reportedly normal. The jaw was dislocated to the left, and there was diffuse abdominal tenderness. Intravenous morphine, diphenhydramine, and ondansetron were administered; an infusion of dextrose was started; and the dislocated jaw was manually reduced. The patient was admitted to the other hospital. The next day, the severity of pain in the abdomen and rash increased. Transfer to this hospital was requested because of a shortage of hemin at the other hospital.
On evaluation at this hospital, the patient described intense pain in the abdomen, a painful rash, and persistent nausea, agitation, and confusion. She was worried that she might have seizures, have blistering of the skin, or die because the hemin infusion had been delayed. Additional history was obtained from the patient. She had a history of obesity, anxiety, and chronic pain that had been attributed to acute intermittent porphyria. She reported that acute intermittent porphyria had been diagnosed 13 years before this admission, when abdominal pain, jerking movements of the right arm and leg, and a painful rash developed during menarche. During the 13 years before this admission, one or two flares of acute intermittent porphyria had occurred each year; during the 6 months before this admission, no flares had occurred.
Two previous flares of acute intermittent porphyria had been treated with a hemin infusion. During the first hemin infusion, the patient had a reaction that was characterized by intense yelling and writhing in pain, and intubation was performed to complete the infusion. Before the second hemin infusion, she received intravenous methylprednisolone and underwent elective intubation to prevent a reaction. The patient identified heat, stress, and menses as triggers for acute intermittent porphyria flares.
Medications included intravenous diphenhydramine and dextrose, which were administered daily through a central-venous-access port in the right side of the chest. The patient had previously taken intravenous morphine daily; however, she had not had access to this medication for approximately 3 months because of an inability to transport it from her home in the United Kingdom. Nonsteroidal antiinflammatory drugs and penicillin had caused anaphylaxis, prochlorperazine had caused flushing, metoclopramide had caused anxiety, and fentanyl had caused altered mental status.
The patient was born in New England and had moved to the United Kingdom 15 years earlier. She was a student in a graduate program at a university in the United Kingdom and had returned to New England to visit her family. She did not use alcohol or illicit drugs, and she did not vape or smoke cigarettes. Her mother had dementia, and her father had died years earlier from an unknown cause. Her maternal grandmother had acute intermittent porphyria. Her immediate family had undergone genetic testing for acute intermittent porphyria; her brother was an asymptomatic carrier of a pathogenic variant, and her six other siblings were not carriers.
On examination, the temperature was 36.3°C, the blood pressure 144/90 mm Hg, the heart rate 100 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. She appeared older than her stated age. She was awake, alert, and oriented. She was frustrated and irritable, with pressured speech. A port in the right side of the chest was palpated. Tenderness in the abdomen was diffuse but was worst in the right upper quadrant. Erythematous plaques and excoriations were present on the arms and chest and under the breasts. The neurologic examination was normal.
Blood levels of electrolytes, calcium, total protein, albumin, and globulin were normal, as were the results of kidney-function and liver-function tests. The hemoglobin level was 10.6 g per deciliter (reference range, 12.0 to 16.0) and the platelet count 120,000 per microliter (reference range, 150,000 to 400,000). A urine specimen was obtained for measurement of the urinary porphobilinogen (PBG) and porphyrin levels, but the amount of urine was inadequate. Oral acetaminophen and intravenous morphine, diphenhydramine, lorazepam, and ondansetron were administered. Infusions of dextrose and hemin were started, and the patient was admitted to this hospital.
During the subsequent 2 days, the hemin infusion was continued, but the patient’s symptoms did not abate. On the second hospital day, an additional urine specimen was obtained; the urinary PBG level was 0.3 μmol per liter (reference range, 0.0 to 1.3) and the uroporphyrin level 4 nmol per liter (reference range, 0 to 30). On the third hospital day, the patient reported worsening jerking movements of the right arm and leg, which she believed had caused jaw dislocation. On examination, the jaw was dislocated to the left. She did not cooperate with a manual reduction, and a surgical reduction of the jaw was performed.
A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Factitious disorder imposed on self. The patient's symptoms are consistent with her reported history of acute intermittent porphyria, but her urinary PBG and uroporphyrin levels, which would be elevated during a porphyria attack, are normal. This suggests that her symptoms are not due to porphyria. The patient's symptoms also do not improve with treatment for porphyria, further suggesting that her symptoms are not due to this condition. The patient's history of reactions to treatment, including intense yelling and writhing in pain during a hemin infusion, could suggest that she is intentionally producing or exaggerating symptoms. Her history of multiple hospital admissions for similar symptoms, her appearance of being older than her stated age, and her pressured speech could also suggest a factitious disorder. The patient's reported history of anaphylaxis to common medications, which could limit the treatments available to her, could also suggest a factitious disorder. Finally, the patient's dislocated jaw, which she attributes to jerking movements of her arm and leg, could be self-inflicted, further suggesting a factitious disorder.""
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        ""content"": ""The patient's symptoms of abdominal pain, jerking movements of the right arm and leg, and a painful rash are consistent with her previous flares of acute intermittent porphyria. However, her urinary PBG and uroporphyrin levels, which are typically elevated during a porphyria attack, are within normal range. This suggests that her symptoms may not be due to a porphyria attack. The patient's history of anxiety, chronic pain, and her reaction to previous hemin infusions suggest a possible psychogenic cause for her symptoms. The patient's jaw dislocation could be due to self-induced trauma, which is seen in some cases of factitious disorder. \n\nDiagnosis: Factitious disorder.""
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        ""role"": ""assistant"",
        ""content"": ""The patient presents with abdominal pain, jerking movements of the right arm and leg, and a painful rash. She has a history of acute intermittent porphyria, which is characterized by abdominal pain, neuropsychiatric symptoms, and a rash. However, her symptoms did not improve with hemin infusion, which is the standard treatment for acute intermittent porphyria. This suggests that her symptoms may not be due to a flare of acute intermittent porphyria. Other possible diagnoses include a seizure disorder, given her jerking movements and concern about having seizures, and a skin condition such as dermatitis or an allergic reaction, given her painful rash. However, her urinary PBG and uroporphyrin levels were within the normal range, which argues against a diagnosis of acute intermittent porphyria. Furthermore, her neurologic examination was normal, which makes a seizure disorder less likely. Her rash could be due to a skin condition, but it could also be a manifestation of her reported porphyria. Given her history of acute intermittent porphyria, her symptoms, and the lack of improvement with hemin infusion, a diagnosis of porphyria cutanea tarda is possible. This condition is a type of porphyria that can cause skin symptoms and is not typically associated with elevated urinary PBG levels. However, her symptoms could also be due to a functional disorder, given her history of anxiety and chronic pain, her frustration and irritability, and her pressured speech. Functional disorders can cause a wide range of physical symptoms that are not explained by an underlying medical condition.\n\nDiagnosis: Functional disorder.""
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 10.1056/NEJMcpc2211375,Case 12-2023: A 44-Year-Old Woman with Muscle Weakness and Myalgia,,Hypocalcemic myopathy due to hypoparathyroidism,Hypoparathyroidism with symptomatic hypocalcemia,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 44-year-old woman was evaluated in the rheumatology clinic of this hospital because of proximal muscle weakness and myalgia.
The patient had been in her usual state of health until 5 years before the current presentation, when morning stiffness and pain developed in the small joints of both hands. Laboratory evaluation reportedly revealed elevated blood levels of anti–cyclic citrullinated peptide (CCP) antibodies and rheumatoid factor, as well as an elevated erythrocyte sedimentation rate. Rheumatoid arthritis was diagnosed, but the patient chose not to begin specific therapy for rheumatoid arthritis. Instead, she began taking selenium, cod-liver oil, and turmeric as home remedies for joint pain. Morning stiffness and joint pain resolved after 4 weeks.
Four years before the current presentation, treatment with hydroxychloroquine was started after the occurrence of another episode of morning stiffness and pain in the small joints of the hands. Three years before the current presentation, treatment with hydroxychloroquine was stopped after melasma developed. Treatment with methotrexate was initiated, but morning hand stiffness and pain recurred; methotrexate was replaced with leflunomide, and the symptoms in the hands subsequently decreased.
Six months before the current presentation, the patient began to have myalgia in the arms and thighs, as well as generalized fatigue. She had difficulty raising her arms above her head, and she could no longer independently brush her hair or apply makeup. Myalgia worsened with exercise and was worst at the end of the day. The patient reported episodes of tingling in the hands and feet, but she had no stiffness or pain in the small joints of her hands.
Three months before the current presentation, the patient was evaluated by a local rheumatologist and laboratory testing was performed. The blood level of creatine kinase was 422 U per liter (reference range, 40 to 150) and the lactate dehydrogenase level 509 U per liter (reference range, 110 to 210). Antinuclear antibodies (ANA) were detected at a titer of 1:320 in a nuclear homogenous pattern, and anti–U1-ribonucleoprotein (U1-RNP) antibodies were present. The blood levels of C3 and C4 were normal, and testing for anti–double-stranded DNA (dsDNA) and anti-Smith antibodies was negative. Two months before the current presentation, treatment with azathioprine was started, and the patient was referred to the rheumatology clinic of this hospital.
In the rheumatology clinic, the patient reported ongoing myalgia and tingling in the hands and feet but had noticed an improvement in her ability to raise her arms above her head after starting treatment with azathioprine. Two weeks earlier, episodes of muscle spasms in the hands and fingers had developed; massage of the hands had been performed to relax the spasms.
The patient had a history of Graves’ disease, which had been complicated by ophthalmoplegia and had been treated with methimazole for 2 years, followed by radioactive iodine ablation 11 years before this presentation; hypothyroidism had developed after radioactive iodine ablation therapy. Other history included latent tuberculosis infection, which had been treated with a 3-month course of isoniazid and rifampin, and hypoparathyroidism that had developed 9 years before this presentation. Medications included azathioprine, levothyroxine, calcium supplements, and calcitriol; the patient was unsure of the formulation and dose of calcium supplementation. She lived outside the United States and traveled intermittently to Boston for specialized medical care. She lived with her mother and worked in information technology. She drank alcohol occasionally, smoked cigarettes, and used no illicit drugs. A sibling had systemic lupus erythematosus (SLE).
On examination, the temporal temperature was 36.3°C, the blood pressure 145/70 mm Hg, the pulse 72 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She had mild exophthalmos in both eyes. There was an area of hyperpigmentation on the face. The joints had a normal range of motion without tenderness on palpation; there was no synovitis. Neck flexion was mildly weak, as was hip flexion; strength was otherwise normal, as was sensation. There was no rash. The remainder of the examination was normal.
Diagnostic tests were performed, and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 44-year-old woman was evaluated in the rheumatology clinic of this hospital because of proximal muscle weakness and myalgia.
The patient had been in her usual state of health until 5 years before the current presentation, when morning stiffness and pain developed in the small joints of both hands. Laboratory evaluation reportedly revealed elevated blood levels of anti–cyclic citrullinated peptide (CCP) antibodies and rheumatoid factor, as well as an elevated erythrocyte sedimentation rate. Rheumatoid arthritis was diagnosed, but the patient chose not to begin specific therapy for rheumatoid arthritis. Instead, she began taking selenium, cod-liver oil, and turmeric as home remedies for joint pain. Morning stiffness and joint pain resolved after 4 weeks.
Four years before the current presentation, treatment with hydroxychloroquine was started after the occurrence of another episode of morning stiffness and pain in the small joints of the hands. Three years before the current presentation, treatment with hydroxychloroquine was stopped after melasma developed. Treatment with methotrexate was initiated, but morning hand stiffness and pain recurred; methotrexate was replaced with leflunomide, and the symptoms in the hands subsequently decreased.
Six months before the current presentation, the patient began to have myalgia in the arms and thighs, as well as generalized fatigue. She had difficulty raising her arms above her head, and she could no longer independently brush her hair or apply makeup. Myalgia worsened with exercise and was worst at the end of the day. The patient reported episodes of tingling in the hands and feet, but she had no stiffness or pain in the small joints of her hands.
Three months before the current presentation, the patient was evaluated by a local rheumatologist and laboratory testing was performed. The blood level of creatine kinase was 422 U per liter (reference range, 40 to 150) and the lactate dehydrogenase level 509 U per liter (reference range, 110 to 210). Antinuclear antibodies (ANA) were detected at a titer of 1:320 in a nuclear homogenous pattern, and anti–U1-ribonucleoprotein (U1-RNP) antibodies were present. The blood levels of C3 and C4 were normal, and testing for anti–double-stranded DNA (dsDNA) and anti-Smith antibodies was negative. Two months before the current presentation, treatment with azathioprine was started, and the patient was referred to the rheumatology clinic of this hospital.
In the rheumatology clinic, the patient reported ongoing myalgia and tingling in the hands and feet but had noticed an improvement in her ability to raise her arms above her head after starting treatment with azathioprine. Two weeks earlier, episodes of muscle spasms in the hands and fingers had developed; massage of the hands had been performed to relax the spasms.
The patient had a history of Graves’ disease, which had been complicated by ophthalmoplegia and had been treated with methimazole for 2 years, followed by radioactive iodine ablation 11 years before this presentation; hypothyroidism had developed after radioactive iodine ablation therapy. Other history included latent tuberculosis infection, which had been treated with a 3-month course of isoniazid and rifampin, and hypoparathyroidism that had developed 9 years before this presentation. Medications included azathioprine, levothyroxine, calcium supplements, and calcitriol; the patient was unsure of the formulation and dose of calcium supplementation. She lived outside the United States and traveled intermittently to Boston for specialized medical care. She lived with her mother and worked in information technology. She drank alcohol occasionally, smoked cigarettes, and used no illicit drugs. A sibling had systemic lupus erythematosus (SLE).
On examination, the temporal temperature was 36.3°C, the blood pressure 145/70 mm Hg, the pulse 72 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She had mild exophthalmos in both eyes. There was an area of hyperpigmentation on the face. The joints had a normal range of motion without tenderness on palpation; there was no synovitis. Neck flexion was mildly weak, as was hip flexion; strength was otherwise normal, as was sensation. There was no rash. The remainder of the examination was normal.
Diagnostic tests were performed, and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of proximal muscle weakness, myalgia, and tingling in the hands and feet, along with elevated creatine kinase and lactate dehydrogenase levels, suggest a myopathy. The presence of anti-U1-RNP antibodies and a history of rheumatoid arthritis suggest an autoimmune etiology. The patient's improvement with azathioprine, a medication used to treat autoimmune conditions, further supports this. The patient's history of Graves' disease and hypoparathyroidism, both autoimmune conditions, also suggest a predisposition to autoimmune disease. Given these findings, the most likely diagnosis is mixed connective tissue disease (MCTD), an autoimmune condition characterized by features of several connective tissue diseases, including systemic lupus erythematosus, scleroderma, and polymyositis. MCTD is often associated with high titers of anti-U1-RNP antibodies, as seen in this patient.\n\nDiagnosis: Mixed Connective Tissue Disease (MCTD)""
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        ""role"": ""assistant"",
        ""content"": ""The patient's symptoms of proximal muscle weakness, myalgia, and elevated creatine kinase and lactate dehydrogenase levels suggest a myopathy. The presence of anti-U1-RNP antibodies and a history of rheumatoid arthritis suggest a connective tissue disease. The combination of these findings is suggestive of mixed connective tissue disease (MCTD), which is characterized by features of several connective tissue diseases including systemic lupus erythematosus, scleroderma, and polymyositis, and is often associated with high titers of anti-U1-RNP antibodies. \n\nMixed Connective Tissue Disease (MCTD)""
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        ""content"": ""The patient is a 44-year-old woman with a history of rheumatoid arthritis and Graves' disease who presents with proximal muscle weakness, myalgia, and tingling in the hands and feet. The differential diagnosis includes polymyositis, dermatomyositis, systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD). \n\nPolymyositis and dermatomyositis are characterized by muscle weakness and myalgia, but dermatomyositis also presents with a characteristic skin rash, which the patient does not have. Therefore, dermatomyositis is less likely. \n\nSLE can present with a variety of symptoms, including muscle weakness and myalgia. However, the patient's blood levels of C3 and C4 are normal and testing for anti-dsDNA and anti-Smith antibodies is negative, which makes SLE less likely. \n\nMCTD is characterized by features of several connective tissue diseases, including SLE, scleroderma, and polymyositis. The patient's symptoms of muscle weakness and myalgia, as well as the presence of anti-U1-RNP antibodies, are consistent with MCTD. \n\nGiven the patient's symptoms and laboratory findings, MCTD is the most likely diagnosis. \n\nDiagnosis: Mixed Connective Tissue Disease (MCTD)""
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10.1056/NEJMcpc2211516,Case 11-2023: A 67-Year-Old Man with Mantle-Cell Lymphoma and Hypoxemia,"Hematocrit (%)	 	25.2
Hemoglobin (g/dl)	 	7.9
White-cell count (per μl)	 	21,560
Differential count (per μl)		
Neutrophils	 	14,380
Lymphocytes	 	750
Monocytes	 	5280
Eosinophils	 	0
Basophils	 00	190
Metamyelocytes	0	900
Platelet count (per μl)	 	596,000
Mean corpuscular volume (fl)	 	107.7
Lactate dehydrogenase (U/liter)	11 10	382",Dapsone-induced methemoglobinemia.,Dapsone-induced methemoglobinemia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 67-year-old man was admitted to this hospital with hypoxemia.
Six years before the current presentation, the patient was evaluated because of melena and anemia. Esophagogastroduodenoscopy revealed duodenal ulcers; biopsy of one of the ulcers revealed changes consistent with moderately differentiated adenocarcinoma. Computed tomography (CT) of the abdomen showed a locally invasive mass in the head of the pancreas. A diagnosis of pancreatic adenocarcinoma with metastasis to the duodenum was made, and treatment included chemotherapy, chemoradiation, and pancreaticoduodenectomy. Two months after the surgery, surveillance CT of the chest showed segmental pulmonary embolism in the right lower lobe. Treatment with low-molecular-weight heparin was recommended, but the patient declined.
During the next 5 years, surveillance CT of the chest, abdomen, and pelvis was performed every 6 months. Six months before the current presentation, CT of the abdomen showed a new mass in the sigmoid colon with associated nodularity and lymphadenopathy. Colonoscopy revealed two fungating, nonobstructing, medium-sized masses, one at the ileocecal valve and the other in the sigmoid colon. Biopsy was performed, and a diagnosis of mantle-cell lymphoma was established. The patient was evaluated in the oncology clinic of this hospital, and plans were made for treatment with chemotherapy. Five months before the current presentation, pain in the right leg developed after a long car trip. Ultrasonography of the right leg revealed distal deep-vein thrombosis, and treatment with apixaban was initiated.
Nine weeks before the current presentation, cycle 1 of rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) chemotherapy was administered, along with filgrastim. In addition, the administration of acyclovir and trimethoprim–sulfamethoxazole was started for prophylaxis; however, rash developed on the trunk after 1 week, and trimethoprim–sulfamethoxazole was replaced with atovaquone for prophylaxis against Pneumocystis jirovecii pneumonia.
Six weeks before the current presentation, cycle 2 of R-DHAP chemotherapy was administered. Two days later, melena, fatigue, and dyspnea on exertion developed. Laboratory testing revealed anemia (hematocrit, 26.8%; normal range, 41.0 to 53.0). The patient received 2 units of packed red cells, and fatigue and dyspnea resolved. Treatment with omeprazole was initiated. Four weeks before the current presentation, the administration of atovaquone was stopped because of the cost of the medication, and dapsone was started for prophylaxis against P. jirovecii pneumonia.
Three weeks before the current presentation, cycle 3 of R-DHAP chemotherapy was administered. Ultrasonography of the right leg revealed resolution of the distal deep-vein thrombosis, and treatment with apixaban was stopped. Two weeks before the current presentation, fatigue and dyspnea on exertion recurred, but melena did not. Laboratory testing again revealed anemia (hematocrit, 28.7%), and the patient received 1 unit of packed red cells; fatigue resolved, but dyspnea did not.
On the day of presentation, the patient was evaluated before the administration of cycle 4 of R-DHAP chemotherapy. He reported ongoing dyspnea on exertion but no cough, fever, chills, chest pain, or orthopnea. He had been having loose stools since the pancreaticoduodenectomy. Other medical history included hypertension and hereditary spherocytosis, which had been treated with splenectomy. Medications included acyclovir, dapsone, lisinopril, and omeprazole. Trimethoprim–sulfamethoxazole had caused a rash; there were no other known drug allergies. The patient drank alcohol rarely; he had smoked tobacco for 2 years but had quit 20 years before this presentation. He was divorced, lived alone in a suburb of Boston, and worked as a lawyer. His mother had had breast cancer.
On examination, the temporal temperature was 36.6°C, the blood pressure 134/82 mm Hg, the pulse 90 beats per minute, and the respiratory rate 22 breaths per minute. The oxygen saturation was 92% while the patient was at rest and breathing ambient air, 88 to 90% while he was walking and breathing ambient air, and 93% while he was at rest and receiving supplemental oxygen through a nasal cannula at a rate of 6 liters per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.4. The patient had tachypnea but no increased work of breathing. The lung sounds were normal, and the jugular venous pulse was not elevated. The legs had no edema.
Table 1.

Laboratory Data.
The blood levels of glucose and electrolytes were normal, as were the results of coagulation, kidney-function, and liver-function tests. Other laboratory test results are shown in Table 1. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 RNA was negative, as was a respiratory viral panel. An electrocardiogram showed normal sinus rhythm.
Figure 1.

CT Pulmonary Angiogram Obtained on Presentation.
Dr. Jo-Anne O. Shepard: CT pulmonary angiography of the chest (Figure 1), performed after the administration of intravenous contrast material, showed filling defects in the right upper lobe and both lower lobes, findings consistent with pulmonary emboli. Subtle tree-in-bud and ground-glass opacities were present in the upper lobes. Scattered pulmonary nodules were present bilaterally; they were stable in size as compared with nodules observed on previous imaging studies. The main pulmonary artery measured 2.6 cm in diameter proximal to bifurcation.
Dr. Hofacker: Cycle 4 of R-DHAP chemotherapy was delayed. Treatment with intravenous heparin was initiated, and the patient was admitted to the hospital. On the second hospital day, the oxygen saturation was 91% while he was at rest and receiving supplemental oxygen through a nasal cannula at a rate of 5 liters per minute.
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 67-year-old man was admitted to this hospital with hypoxemia.
Six years before the current presentation, the patient was evaluated because of melena and anemia. Esophagogastroduodenoscopy revealed duodenal ulcers; biopsy of one of the ulcers revealed changes consistent with moderately differentiated adenocarcinoma. Computed tomography (CT) of the abdomen showed a locally invasive mass in the head of the pancreas. A diagnosis of pancreatic adenocarcinoma with metastasis to the duodenum was made, and treatment included chemotherapy, chemoradiation, and pancreaticoduodenectomy. Two months after the surgery, surveillance CT of the chest showed segmental pulmonary embolism in the right lower lobe. Treatment with low-molecular-weight heparin was recommended, but the patient declined.
During the next 5 years, surveillance CT of the chest, abdomen, and pelvis was performed every 6 months. Six months before the current presentation, CT of the abdomen showed a new mass in the sigmoid colon with associated nodularity and lymphadenopathy. Colonoscopy revealed two fungating, nonobstructing, medium-sized masses, one at the ileocecal valve and the other in the sigmoid colon. Biopsy was performed, and a diagnosis of mantle-cell lymphoma was established. The patient was evaluated in the oncology clinic of this hospital, and plans were made for treatment with chemotherapy. Five months before the current presentation, pain in the right leg developed after a long car trip. Ultrasonography of the right leg revealed distal deep-vein thrombosis, and treatment with apixaban was initiated.
Nine weeks before the current presentation, cycle 1 of rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) chemotherapy was administered, along with filgrastim. In addition, the administration of acyclovir and trimethoprim–sulfamethoxazole was started for prophylaxis; however, rash developed on the trunk after 1 week, and trimethoprim–sulfamethoxazole was replaced with atovaquone for prophylaxis against Pneumocystis jirovecii pneumonia.
Six weeks before the current presentation, cycle 2 of R-DHAP chemotherapy was administered. Two days later, melena, fatigue, and dyspnea on exertion developed. Laboratory testing revealed anemia (hematocrit, 26.8%; normal range, 41.0 to 53.0). The patient received 2 units of packed red cells, and fatigue and dyspnea resolved. Treatment with omeprazole was initiated. Four weeks before the current presentation, the administration of atovaquone was stopped because of the cost of the medication, and dapsone was started for prophylaxis against P. jirovecii pneumonia.
Three weeks before the current presentation, cycle 3 of R-DHAP chemotherapy was administered. Ultrasonography of the right leg revealed resolution of the distal deep-vein thrombosis, and treatment with apixaban was stopped. Two weeks before the current presentation, fatigue and dyspnea on exertion recurred, but melena did not. Laboratory testing again revealed anemia (hematocrit, 28.7%), and the patient received 1 unit of packed red cells; fatigue resolved, but dyspnea did not.
On the day of presentation, the patient was evaluated before the administration of cycle 4 of R-DHAP chemotherapy. He reported ongoing dyspnea on exertion but no cough, fever, chills, chest pain, or orthopnea. He had been having loose stools since the pancreaticoduodenectomy. Other medical history included hypertension and hereditary spherocytosis, which had been treated with splenectomy. Medications included acyclovir, dapsone, lisinopril, and omeprazole. Trimethoprim–sulfamethoxazole had caused a rash; there were no other known drug allergies. The patient drank alcohol rarely; he had smoked tobacco for 2 years but had quit 20 years before this presentation. He was divorced, lived alone in a suburb of Boston, and worked as a lawyer. His mother had had breast cancer.
On examination, the temporal temperature was 36.6°C, the blood pressure 134/82 mm Hg, the pulse 90 beats per minute, and the respiratory rate 22 breaths per minute. The oxygen saturation was 92% while the patient was at rest and breathing ambient air, 88 to 90% while he was walking and breathing ambient air, and 93% while he was at rest and receiving supplemental oxygen through a nasal cannula at a rate of 6 liters per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.4. The patient had tachypnea but no increased work of breathing. The lung sounds were normal, and the jugular venous pulse was not elevated. The legs had no edema.
Table 1.

Laboratory Data.
The blood levels of glucose and electrolytes were normal, as were the results of coagulation, kidney-function, and liver-function tests. Other laboratory test results are shown in Table 1. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 RNA was negative, as was a respiratory viral panel. An electrocardiogram showed normal sinus rhythm.
Figure 1.

CT Pulmonary Angiogram Obtained on Presentation.
Dr. Jo-Anne O. Shepard: CT pulmonary angiography of the chest (Figure 1), performed after the administration of intravenous contrast material, showed filling defects in the right upper lobe and both lower lobes, findings consistent with pulmonary emboli. Subtle tree-in-bud and ground-glass opacities were present in the upper lobes. Scattered pulmonary nodules were present bilaterally; they were stable in size as compared with nodules observed on previous imaging studies. The main pulmonary artery measured 2.6 cm in diameter proximal to bifurcation.
Dr. Hofacker: Cycle 4 of R-DHAP chemotherapy was delayed. Treatment with intravenous heparin was initiated, and the patient was admitted to the hospital. On the second hospital day, the oxygen saturation was 91% while he was at rest and receiving supplemental oxygen through a nasal cannula at a rate of 5 liters per minute.
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of pancreatic adenocarcinoma, mantle-cell lymphoma, and hereditary spherocytosis. He has been treated with chemotherapy and has recently developed hypoxemia. His CT scan shows pulmonary emboli and ground-glass opacities. Given his history of malignancy, chemotherapy, and recent switch from atovaquone to dapsone for Pneumocystis jirovecii pneumonia prophylaxis, the most likely diagnosis is Pneumocystis jirovecii pneumonia (PJP). PJP is a common opportunistic infection in immunocompromised patients, particularly those with HIV/AIDS, but it can also occur in patients with malignancies or those receiving immunosuppressive therapy. The ground-glass opacities seen on the CT scan are a common finding in PJP.\n\nDiagnosis: Pneumocystis jirovecii pneumonia (PJP)""
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        ""content"": ""The patient is a 67-year-old man with a history of pancreatic adenocarcinoma, mantle-cell lymphoma, and hereditary spherocytosis. He presents with hypoxemia, dyspnea on exertion, and anemia. The differential diagnosis for this patient includes pulmonary embolism, pneumonia, anemia, and side effects from chemotherapy. The patient has a history of pulmonary embolism and deep vein thrombosis, which makes another pulmonary embolism a likely possibility. The patient's CT scan shows filling defects in the right upper lobe and both lower lobes, which is consistent with pulmonary emboli. The patient also has ground-glass opacities in the upper lobes, which could suggest pneumonia. However, the patient does not have a fever or cough, which makes pneumonia less likely. The patient's anemia could also be contributing to his dyspnea, but his symptoms did not completely resolve after receiving packed red cells. The patient's chemotherapy could also be causing his symptoms, but his symptoms did not resolve after delaying his chemotherapy. Given the patient's history and CT findings, a pulmonary embolism is the most likely diagnosis.\n\nDiagnosis: Pulmonary embolism.""
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10.1056/NEJMcpc2211365,Case 10-2023: A 27-Year-Old Man with Convulsions,,Functional seizures.,Functional seizures.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 27-year-old man was admitted to this hospital because of convulsions.
The patient had been in his usual state of health until 2 years before this admission, when shaking of the trunk, arms, and legs occurred. The episode lasted approximately 4 to 5 minutes and had been preceded by a sharp pain in the back of the head that radiated to the neck, blurred vision, palpitations, nausea, and difficulty concentrating. The patient did not seek evaluation, and no additional convulsive episodes occurred during the subsequent 20 months.
Four months before this admission, while the patient was drinking alcohol at a party, his body suddenly became stiff, and he fell backward onto a table. Shaking of the trunk, arms, and legs occurred for approximately 5 to 8 minutes. He had urinary incontinence but did not bite his tongue. Five minutes later, similar convulsions occurred. The patient was taken to the emergency department of another hospital for evaluation. The results of computed tomography of the head were normal, as was an electroencephalogram (EEG) that was obtained over a period of 40 minutes. Treatment with levetiracetam was started. The patient was discharged home with a recommendation for follow-up evaluation at the neurology clinic of the other hospital.
Three months before this admission, the patient was evaluated at the neurology clinic of the other hospital. He reported that despite the use of levetiracetam, convulsions occurred approximately once per week. The results of magnetic resonance imaging (MRI) of the head, performed before and after the administration of intravenous contrast material, were reportedly normal. Treatment with lamotrigine was started. There was no change in the quality or frequency of the convulsive episodes.
One month before this admission, while the patient was at work, his colleagues found him on the floor, and they witnessed “shaking and clenching” movements of the trunk, arms, and legs that lasted approximately 2 minutes. Emergency medical services were called, and the patient was taken to the emergency department of a second hospital for evaluation.
At least two additional convulsive episodes occurred at the second hospital. During one episode, the shaking movements became less intense when the physician’s hand was placed on the patient’s shoulder; the movements resumed at the previous intensity when the hand was removed. In addition, the patient’s eyes were closed. When the eyelids were opened manually, no nystagmus or gaze deviation was present. When the eyelids were released, the eyes shut forcefully and Bell’s phenomenon (upward deviation of the eyes when closing) occurred. The patient did not speak but was able to follow simple verbal commands, such as an instruction to squeeze the physician’s hands. In between the convulsive episodes, there were intermittent rocking movements of the upper body and nonrhythmic tremulous movements of the hands, and the patient did not speak or follow commands. After several hours, the episodes stopped, and the patient was able to speak. Admission to the hospital was recommended; however, the patient declined because of work obligations and anxiety about being in the hospital. He was discharged home.
During the subsequent month, the patient continued to take levetiracetam and lamotrigine. However, the convulsions increased in frequency to one to three times per week.
On the morning before the current admission, while the patient was at work, his colleagues noticed that he abruptly stopped speaking and began to have shaking movements of the arms and legs. Emergency medical services were called. On their arrival, the patient’s body was stiff, and there was twitching of the trunk, arms, and legs. No urinary or fecal incontinence or biting of the tongue had occurred. The patient was able to stand up from a chair and walk to the ambulance. He was brought to the emergency department of this hospital.
On examination, the temperature was 36.2°C, the blood pressure 111/56 mm Hg, the pulse 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. He was awake and alert but did not speak. His eyes were open, with a primary midline gaze and blinking in response to visual threat. His body appeared stiff, with the arms and legs straightened. There were intermittent nonrhythmic tremulous movements of the trunk, arms, and legs. The patient was able to follow complex commands and to move the arms and legs symmetrically and against gravity, but there was a delay in motor activation. The deep-tendon reflexes were normal. Extensive scarring from burns was present on the face, trunk, back, arms, and legs.
Approximately 45 minutes after the tremulous movements had stopped, the patient was able to speak but with limited fluency. Additional history was obtained. He had been taking levetiracetam and lamotrigine as directed; however, 3 days before this evaluation, he had stopped taking these medications because he was unsure whether they were effective. That morning, he had felt well until he noticed a sharp pain in the back of his head that radiated to his neck, along with sudden blurred vision, full-body numbness, and difficulty concentrating. A convulsive episode then occurred that lasted up to 20 minutes; during the episode, the patient was aware of events but sometimes had difficulty hearing. He described his overall mood as “pretty good” and did not report decreased energy or chronic fatigue. There was no history of psychotic or manic symptoms, suicidal ideation, or obsessive or compulsive behaviors.
The patient had a history of a febrile seizure in childhood, as well as several concussions that had occurred while he was playing sports in childhood. He reported that during the first 6 years of life, his social supports were limited, and he had experienced maltreatment by a family member; he did not elaborate on the nature of the maltreatment. In late childhood, he was involved in a house fire and hospitalized for a prolonged period because of severe burns on the face, body, arms, and legs. He had asthma, major depressive disorder, chronic post-traumatic stress disorder (PTSD), and panic disorder with agoraphobia. He took escitalopram daily and lorazepam as needed for panic attacks. He was in a long-term romantic relationship. He did not smoke cigarettes or use illicit drugs; he smoked marijuana approximately once per year and drank one alcoholic beverage per week. His father had died of heart disease when the patient was a teenager; his mother had schizoaffective disorder and post-traumatic epilepsy.
Blood levels of glucose and electrolytes were normal, as were the results of liver-function and kidney-function tests. The blood lactate level was 2.4 mmol per liter (22 mg per deciliter; reference range, 0.5 to 2.2 mmol per liter [5 to 20 mg per deciliter]) and the blood creatine kinase level 489 U per liter (reference range, 60 to 400). Serum and urine toxicologic panels were negative. An electrocardiogram showed normal sinus rhythm. The patient was admitted to this hospital.
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 27-year-old man was admitted to this hospital because of convulsions.
The patient had been in his usual state of health until 2 years before this admission, when shaking of the trunk, arms, and legs occurred. The episode lasted approximately 4 to 5 minutes and had been preceded by a sharp pain in the back of the head that radiated to the neck, blurred vision, palpitations, nausea, and difficulty concentrating. The patient did not seek evaluation, and no additional convulsive episodes occurred during the subsequent 20 months.
Four months before this admission, while the patient was drinking alcohol at a party, his body suddenly became stiff, and he fell backward onto a table. Shaking of the trunk, arms, and legs occurred for approximately 5 to 8 minutes. He had urinary incontinence but did not bite his tongue. Five minutes later, similar convulsions occurred. The patient was taken to the emergency department of another hospital for evaluation. The results of computed tomography of the head were normal, as was an electroencephalogram (EEG) that was obtained over a period of 40 minutes. Treatment with levetiracetam was started. The patient was discharged home with a recommendation for follow-up evaluation at the neurology clinic of the other hospital.
Three months before this admission, the patient was evaluated at the neurology clinic of the other hospital. He reported that despite the use of levetiracetam, convulsions occurred approximately once per week. The results of magnetic resonance imaging (MRI) of the head, performed before and after the administration of intravenous contrast material, were reportedly normal. Treatment with lamotrigine was started. There was no change in the quality or frequency of the convulsive episodes.
One month before this admission, while the patient was at work, his colleagues found him on the floor, and they witnessed “shaking and clenching” movements of the trunk, arms, and legs that lasted approximately 2 minutes. Emergency medical services were called, and the patient was taken to the emergency department of a second hospital for evaluation.
At least two additional convulsive episodes occurred at the second hospital. During one episode, the shaking movements became less intense when the physician’s hand was placed on the patient’s shoulder; the movements resumed at the previous intensity when the hand was removed. In addition, the patient’s eyes were closed. When the eyelids were opened manually, no nystagmus or gaze deviation was present. When the eyelids were released, the eyes shut forcefully and Bell’s phenomenon (upward deviation of the eyes when closing) occurred. The patient did not speak but was able to follow simple verbal commands, such as an instruction to squeeze the physician’s hands. In between the convulsive episodes, there were intermittent rocking movements of the upper body and nonrhythmic tremulous movements of the hands, and the patient did not speak or follow commands. After several hours, the episodes stopped, and the patient was able to speak. Admission to the hospital was recommended; however, the patient declined because of work obligations and anxiety about being in the hospital. He was discharged home.
During the subsequent month, the patient continued to take levetiracetam and lamotrigine. However, the convulsions increased in frequency to one to three times per week.
On the morning before the current admission, while the patient was at work, his colleagues noticed that he abruptly stopped speaking and began to have shaking movements of the arms and legs. Emergency medical services were called. On their arrival, the patient’s body was stiff, and there was twitching of the trunk, arms, and legs. No urinary or fecal incontinence or biting of the tongue had occurred. The patient was able to stand up from a chair and walk to the ambulance. He was brought to the emergency department of this hospital.
On examination, the temperature was 36.2°C, the blood pressure 111/56 mm Hg, the pulse 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. He was awake and alert but did not speak. His eyes were open, with a primary midline gaze and blinking in response to visual threat. His body appeared stiff, with the arms and legs straightened. There were intermittent nonrhythmic tremulous movements of the trunk, arms, and legs. The patient was able to follow complex commands and to move the arms and legs symmetrically and against gravity, but there was a delay in motor activation. The deep-tendon reflexes were normal. Extensive scarring from burns was present on the face, trunk, back, arms, and legs.
Approximately 45 minutes after the tremulous movements had stopped, the patient was able to speak but with limited fluency. Additional history was obtained. He had been taking levetiracetam and lamotrigine as directed; however, 3 days before this evaluation, he had stopped taking these medications because he was unsure whether they were effective. That morning, he had felt well until he noticed a sharp pain in the back of his head that radiated to his neck, along with sudden blurred vision, full-body numbness, and difficulty concentrating. A convulsive episode then occurred that lasted up to 20 minutes; during the episode, the patient was aware of events but sometimes had difficulty hearing. He described his overall mood as “pretty good” and did not report decreased energy or chronic fatigue. There was no history of psychotic or manic symptoms, suicidal ideation, or obsessive or compulsive behaviors.
The patient had a history of a febrile seizure in childhood, as well as several concussions that had occurred while he was playing sports in childhood. He reported that during the first 6 years of life, his social supports were limited, and he had experienced maltreatment by a family member; he did not elaborate on the nature of the maltreatment. In late childhood, he was involved in a house fire and hospitalized for a prolonged period because of severe burns on the face, body, arms, and legs. He had asthma, major depressive disorder, chronic post-traumatic stress disorder (PTSD), and panic disorder with agoraphobia. He took escitalopram daily and lorazepam as needed for panic attacks. He was in a long-term romantic relationship. He did not smoke cigarettes or use illicit drugs; he smoked marijuana approximately once per year and drank one alcoholic beverage per week. His father had died of heart disease when the patient was a teenager; his mother had schizoaffective disorder and post-traumatic epilepsy.
Blood levels of glucose and electrolytes were normal, as were the results of liver-function and kidney-function tests. The blood lactate level was 2.4 mmol per liter (22 mg per deciliter; reference range, 0.5 to 2.2 mmol per liter [5 to 20 mg per deciliter]) and the blood creatine kinase level 489 U per liter (reference range, 60 to 400). Serum and urine toxicologic panels were negative. An electrocardiogram showed normal sinus rhythm. The patient was admitted to this hospital.
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Psychogenic Non-Epileptic Seizures (PNES)\n\nThe patient's history of trauma, PTSD, and panic disorder with agoraphobia, along with the nature of his seizures, suggest a psychogenic origin. The seizures are not associated with loss of consciousness, and the patient is able to follow commands during the episodes. The seizures also stop when the physician's hand is placed on the patient's shoulder, and resume when the hand is removed. These are all characteristics of psychogenic non-epileptic seizures. Additionally, the patient's seizures did not respond to anti-epileptic drugs, and tests such as EEG and MRI were normal, ruling out an epileptic origin.""
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        ""content"": ""The patient is a 27-year-old male presenting with recurrent convulsions. The differential diagnosis for this patient includes epilepsy, psychogenic non-epileptic seizures (PNES), and panic disorder. The patient has a history of febrile seizures in childhood and several concussions, which could potentially predispose him to epilepsy. However, the patient's seizures have not responded to anti-epileptic medications, and both CT and MRI scans of the head were normal, making epilepsy less likely. The patient also has a history of panic disorder with agoraphobia, and his seizures are often preceded by symptoms such as blurred vision, palpitations, and difficulty concentrating, which could be indicative of a panic attack. However, the patient's seizures are also accompanied by urinary incontinence and last for several minutes, which is not typical of panic disorder. The patient also has a history of major depressive disorder, PTSD, and childhood maltreatment, and his seizures often occur in stressful situations and are accompanied by a sense of awareness, which is suggestive of PNES. Additionally, the patient's seizures have not responded to anti-epileptic medications but do respond to physical touch, further suggesting PNES. \n\nDiagnosis: Psychogenic non-epileptic seizures (PNES)""
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10.1056/NEJMcpc2211356,Case 9-2023: A 20-Year-Old Man with Shortness of Breath and Proteinuria,"Hemoglobin (g/dl)	 	11.3	 	8.7
Hematocrit (%)	42.0–52.0	35.2	 	26.3
White-cell count (per μl)	 	9500	 	7310
Differential count (per μl)				
Neutrophils	 	7590	 	5940
Lymphocytes	900–5400	1270	 	710
Monocytes	10 00	550	 	420
Eosinophils	 00	0	 	190
Basophils	 00	10	 00	20
Platelet count (per μl)	 	296,000	 	213,000
Urea nitrogen (mg/dl)	 	13	 	13
Creatinine (mg/dl)	0.50–1.14	1.14	 	0.98
Lactic acid (mmol/liter)	0.4–2.0	1.1	 	0.6
Albumin (g/dl)	 	1.3	 	1.6
Globulin (g/dl)	2. .5	4.7	2. .5	3.4
Urine				
Bilirubin	—	—	Negative	Negative
Blood	—	—	Negative	2+
Glucose	—	—	Negative	Negative
Ketones	—	—	Negative	Negative
Leukocyte esterase	—	—	Negative	Negative
Nitrites	—	—	Negative	Negative
Protein	—	—	Negative	3+
Red cells (per high-power field)	—	—	 	5–10
White cells (per high-power field)	—	—	 	3–5
Hyaline casts (per high-power field)	—	—	 	1 0",Systemic lupus erythematosus with membranous lupus nephritis,Systemic lupus erythematosus.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 20-year-old man with bipolar disorder was transferred to this hospital because of hemoptysis and hypoxemia.
Eleven months before the current presentation, the patient received a diagnosis of bipolar disorder. Six weeks before the current presentation, he was taken to another hospital for evaluation of racing thoughts, generalized hyperactivity, and difficulty sleeping. He was admitted to a psychiatric hospital for treatment. During the admission, the patient was involved in an altercation and was struck on the left side of the chest; pain subsequently developed in that area. Five weeks before the current presentation, chest pain persisted, and nausea, vomiting, and decreased appetite developed. The patient was transported from the psychiatric hospital to the emergency department of the other hospital for evaluation. Imaging studies were obtained.
Figure 1.

Initial Imaging Studies.
Dr. Teresa Victoria: Computed tomography (CT) of the chest (Figure 1A) revealed ground-glass opacities in the left lower lobe.
Dr. Ravicz: The patient was told that he had a pulmonary contusion and was transported back to the psychiatric hospital. The dosages of quetiapine and paliperidone were increased. Four weeks before the current presentation, the patient had urticaria and intermittent nausea; a single dose of methylprednisolone was administered. Three weeks before the current presentation, the patient was discharged home.
Ten days before the current presentation, chest pain continued, cough developed, and nausea increased in severity. The patient was evaluated in the emergency department of a second hospital. Imaging studies were obtained.
Dr. Victoria: Radiography of the chest (Figure 1B) revealed a consolidation in the left lower lobe and a left pleural effusion.
Dr. Ravicz: A course of doxycycline was started for the treatment of presumed pneumonia, and the patient was discharged home. During the subsequent 6 days, the cough and chest pain abated. Four days before the current presentation, the course of doxycycline was completed. During the next several days, the cough increased in severity and became productive of yellow sputum with dark-red streaks, and shortness of breath developed; nausea also increased in severity. One day before the current presentation, the patient was evaluated again in the emergency department of the second hospital.
Table 1.

Laboratory Data.
On evaluation, the patient appeared ill and had difficulty breathing. The temporal temperature was 37.5°C, the blood pressure 99/50 mm Hg, the heart rate 127 beats per minute, the respiratory rate 31 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air. The hemoglobin level was 11.3 g per deciliter (reference range, 14.0 to 18.0) and the albumin level 1.3 g per deciliter (reference range, 3.4 to 5.0). Blood levels of electrolytes and glucose were normal, as were the results of liver-function tests. Nucleic acid amplification testing of a nasopharyngeal swab was negative for influenza A and B viruses, respiratory syncytial virus, and severe acute respiratory syndrome coronavirus 2. Other laboratory test results are shown in Table 1. Blood was obtained for culture, and additional imaging studies were obtained.
Figure 2.

Imaging Studies Obtained on Current Presentation.
Dr. Victoria: CT angiography of the chest, performed after the administration of intravenous contrast material, revealed emboli of the right and left pulmonary arteries that extended into multiple segmental and subsegmental branches (Figure 2). There were wedge-shaped opacities without enhancement in the left upper and lower lobes, findings consistent with infarction. There were small pleural effusions that were larger on the left side than on the right side.
Dr. Ravicz: Treatment with enoxaparin, vancomycin, and cefepime was started, and intravenous fluids were administered. The patient was admitted to the second hospital. On hospital day 2, the oxygen saturation decreased, and supplemental oxygen was administered through a nasal cannula. Blood cultures showed no growth. The patient was transferred to this hospital for additional evaluation and treatment.
On admission to this hospital, additional history was obtained. The chest pain, cough, hemoptysis, shortness of breath, and nausea continued. The patient reported fatigue and weight loss that had started after the injury to the chest. He had also noticed discoloration in his fingers that was associated with changes in temperature. There was no headache, abdominal pain, or joint pain.
The patient had a history of asthma, migraines, and attention deficit–hyperactivity disorder. Bipolar disorder had been diagnosed when he was hospitalized for mania, grandiose thoughts, and paranoid delusions. Medications included quetiapine, paliperidone, and methylphenidate. Sulfa drugs and valproate had caused rash, nausea, and vomiting. The patient had previously been sexually active with female partners. He drank alcohol rarely and vaped marijuana frequently; he did not smoke tobacco or use illicit drugs. His mother, maternal aunt, paternal aunt, and paternal uncle had depression.
On examination, the temperature was 38.6°C, the blood pressure 89/40 mm Hg, the heart rate 121 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. The right lung was clear on auscultation, but the left lung had diminished sounds. There was no abdominal tenderness, joint swelling, or rash. The patient had a flat affect, apathy, grandiose thoughts, poverty of speech and thought, and psychomotor retardation. There was no evidence of paranoia or hallucinations. The hemoglobin level was 8.7 g per deciliter and the albumin level 1.6 g per deciliter. Urinalysis revealed 2+ blood and 3+ protein; other laboratory test results are shown in Table 1.
Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 20-year-old man with bipolar disorder was transferred to this hospital because of hemoptysis and hypoxemia.
Eleven months before the current presentation, the patient received a diagnosis of bipolar disorder. Six weeks before the current presentation, he was taken to another hospital for evaluation of racing thoughts, generalized hyperactivity, and difficulty sleeping. He was admitted to a psychiatric hospital for treatment. During the admission, the patient was involved in an altercation and was struck on the left side of the chest; pain subsequently developed in that area. Five weeks before the current presentation, chest pain persisted, and nausea, vomiting, and decreased appetite developed. The patient was transported from the psychiatric hospital to the emergency department of the other hospital for evaluation. Imaging studies were obtained.
Figure 1.

Initial Imaging Studies.
Dr. Teresa Victoria: Computed tomography (CT) of the chest (Figure 1A) revealed ground-glass opacities in the left lower lobe.
Dr. Ravicz: The patient was told that he had a pulmonary contusion and was transported back to the psychiatric hospital. The dosages of quetiapine and paliperidone were increased. Four weeks before the current presentation, the patient had urticaria and intermittent nausea; a single dose of methylprednisolone was administered. Three weeks before the current presentation, the patient was discharged home.
Ten days before the current presentation, chest pain continued, cough developed, and nausea increased in severity. The patient was evaluated in the emergency department of a second hospital. Imaging studies were obtained.
Dr. Victoria: Radiography of the chest (Figure 1B) revealed a consolidation in the left lower lobe and a left pleural effusion.
Dr. Ravicz: A course of doxycycline was started for the treatment of presumed pneumonia, and the patient was discharged home. During the subsequent 6 days, the cough and chest pain abated. Four days before the current presentation, the course of doxycycline was completed. During the next several days, the cough increased in severity and became productive of yellow sputum with dark-red streaks, and shortness of breath developed; nausea also increased in severity. One day before the current presentation, the patient was evaluated again in the emergency department of the second hospital.
Table 1.

Laboratory Data.
On evaluation, the patient appeared ill and had difficulty breathing. The temporal temperature was 37.5°C, the blood pressure 99/50 mm Hg, the heart rate 127 beats per minute, the respiratory rate 31 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air. The hemoglobin level was 11.3 g per deciliter (reference range, 14.0 to 18.0) and the albumin level 1.3 g per deciliter (reference range, 3.4 to 5.0). Blood levels of electrolytes and glucose were normal, as were the results of liver-function tests. Nucleic acid amplification testing of a nasopharyngeal swab was negative for influenza A and B viruses, respiratory syncytial virus, and severe acute respiratory syndrome coronavirus 2. Other laboratory test results are shown in Table 1. Blood was obtained for culture, and additional imaging studies were obtained.
Figure 2.

Imaging Studies Obtained on Current Presentation.
Dr. Victoria: CT angiography of the chest, performed after the administration of intravenous contrast material, revealed emboli of the right and left pulmonary arteries that extended into multiple segmental and subsegmental branches (Figure 2). There were wedge-shaped opacities without enhancement in the left upper and lower lobes, findings consistent with infarction. There were small pleural effusions that were larger on the left side than on the right side.
Dr. Ravicz: Treatment with enoxaparin, vancomycin, and cefepime was started, and intravenous fluids were administered. The patient was admitted to the second hospital. On hospital day 2, the oxygen saturation decreased, and supplemental oxygen was administered through a nasal cannula. Blood cultures showed no growth. The patient was transferred to this hospital for additional evaluation and treatment.
On admission to this hospital, additional history was obtained. The chest pain, cough, hemoptysis, shortness of breath, and nausea continued. The patient reported fatigue and weight loss that had started after the injury to the chest. He had also noticed discoloration in his fingers that was associated with changes in temperature. There was no headache, abdominal pain, or joint pain.
The patient had a history of asthma, migraines, and attention deficit–hyperactivity disorder. Bipolar disorder had been diagnosed when he was hospitalized for mania, grandiose thoughts, and paranoid delusions. Medications included quetiapine, paliperidone, and methylphenidate. Sulfa drugs and valproate had caused rash, nausea, and vomiting. The patient had previously been sexually active with female partners. He drank alcohol rarely and vaped marijuana frequently; he did not smoke tobacco or use illicit drugs. His mother, maternal aunt, paternal aunt, and paternal uncle had depression.
On examination, the temperature was 38.6°C, the blood pressure 89/40 mm Hg, the heart rate 121 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. The right lung was clear on auscultation, but the left lung had diminished sounds. There was no abdominal tenderness, joint swelling, or rash. The patient had a flat affect, apathy, grandiose thoughts, poverty of speech and thought, and psychomotor retardation. There was no evidence of paranoia or hallucinations. The hemoglobin level was 8.7 g per deciliter and the albumin level 1.6 g per deciliter. Urinalysis revealed 2+ blood and 3+ protein; other laboratory test results are shown in Table 1.
Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Goodpasture's syndrome. The patient's symptoms of hemoptysis, hypoxemia, and pulmonary infarction, along with the presence of blood and protein in the urine, suggest a disease affecting both the lungs and kidneys. The presence of anti-glomerular basement membrane antibodies in the blood is a key diagnostic marker for Goodpasture's syndrome, an autoimmune disease that causes the body's immune system to attack the lungs and kidneys.""
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        ""content"": ""The patient's symptoms of chest pain, cough, hemoptysis, shortness of breath, and nausea, along with the imaging findings of pulmonary emboli and infarction, suggest a pulmonary condition. The patient's history of bipolar disorder and the use of quetiapine and paliperidone, which are known to increase the risk of venous thromboembolism, further support this. The patient's history of asthma and the recent chest injury could have contributed to the development of the pulmonary emboli. The patient's low hemoglobin and albumin levels suggest chronic disease or malnutrition, which could have made him more susceptible to infection or other complications. The patient's report of discoloration in his fingers associated with changes in temperature suggests Raynaud's phenomenon, which can be associated with connective tissue diseases. However, the patient does not have other symptoms of connective tissue disease, such as joint pain or rash. The patient's urinalysis results of 2+ blood and 3+ protein suggest kidney involvement, which could be due to a systemic disease such as vasculitis. However, the patient does not have other symptoms of vasculitis, such as fever, weight loss, or night sweats. Therefore, the most likely diagnosis is pulmonary embolism secondary to the use of antipsychotic medications and the recent chest injury.\n\nDiagnosis: Pulmonary embolism.""
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        ""content"": ""The patient is a 20-year-old male with a history of bipolar disorder, presenting with hemoptysis, hypoxemia, chest pain, cough, and nausea. He also has a history of asthma, migraines, and attention deficit\u2013hyperactivity disorder. The patient's symptoms started after a chest injury. The differential diagnosis for this patient includes pulmonary embolism, pneumonia, lung contusion, and lung cancer. The patient's CT angiography of the chest revealed emboli of the right and left pulmonary arteries that extended into multiple segmental and subsegmental branches, findings consistent with pulmonary embolism. There were also wedge-shaped opacities without enhancement in the left upper and lower lobes, findings consistent with infarction. The patient's blood cultures showed no growth, making pneumonia less likely. The patient's symptoms started after a chest injury, but the CT angiography of the chest did not show any signs of lung contusion. The patient is young and does not have a history of smoking, making lung cancer less likely. The patient's symptoms, along with the findings from the CT angiography of the chest, are most consistent with pulmonary embolism.\n\nDiagnosis: Pulmonary embolism.""
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10.1056/NEJMcpc2211370,Case 8-2023: A 71-Year-Old Woman with Refractory Hemolytic Anemia,"Hematocrit (%)	33.0–44.0	20.8	 	14.8
Hemoglobin (g/dl)	 	7.0	 	5.3
White-cell count (per μl)	4100–9300	11,200	 	13,340
Differential count (%)				
Neutrophils	 	52	 	82.1
Lymphocytes	28–42	12	 	13.4
Monocytes	4. .5	5.0	 	1.8
Eosinophils	0–5	0	 	0.9
Platelet count (per μl)	130,00 50,000	230,000	 	43,000
Mean corpuscular volume (fl)	82.3–93.2	106.7	 	101.4
Mean corpuscular hemoglobin (pg)	22.2–33.2	35.5	26. 4.0	36.3
Mean corpuscular hemoglobin concentration (g/dl)	32.5–35.1	33.7	31. 7.0	35.8
Red-cell distribution width (%)	12. .0	22.0	 	34.8
Reticulocyte count (%)	0.4–2.0	13.4	0.7–2.5	15.8
Prothrombin time (sec)	9.4–12.3	11.9	 	16.8
Prothrombin-time international normalized ratio	 	1.0	 	1.4
Activated partial-thromboplastin time (sec)	23.6–32.9	24.6	22. 6.0	25.2
Fibrinogen (mg/dl)	172–400	330	15 0	374
d-dimer (ng/ml)	 	5021	 	9321
Haptoglobin (mg/dl)	25–234	<15	3 00	 
Lactate dehydrogenase (U/liter)	8 25	675	11 10	5896
Ferritin (μg/liter)	—	—	1 00	18,050
Total bilirubin (mg/dl)	0.1–1.2	2.8	0.0–1.0	4.1
Direct bilirubin (mg/dl)	0.0–0.3	0.5	0. 	0.4
Albumin (g/dl)	3.5–5.2	4.4	 	3.8
Alanine aminotransferase (U/liter)	6–60	36	 	58
Aspartate aminotransferase (U/liter)	5–45	68	 	135
Alkaline phosphatase (U/liter)	3 5	39	 	77",Breast cancer–associated thrombotic microangiopathy.,Cancer-associated thrombotic microangiopathy due to metastatic breast cancer in the bone marrow.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 71-year-old woman was admitted to this hospital because of refractory hemolytic anemia.
The patient, who had recurrent breast cancer and diffuse cutaneous systemic sclerosis, had been in her usual state of health until 7 months before the current admission, when fatigue and dyspnea on exertion developed. She was reportedly evaluated by a cardiologist and a pulmonologist, but no cause for her symptoms was identified.
Table 1.

Laboratory Data.
Two months before the current admission, dyspnea on exertion worsened, palpitations and dizziness developed, and the patient presented to another hospital for evaluation. Laboratory studies revealed anemia, a low blood level of haptoglobin, and an elevated blood level of lactate dehydrogenase. The blood levels of electrolytes were normal, as were the results of kidney-function tests; other laboratory test results are shown in Table 1. A peripheral-blood smear showed schistocytes. A direct antiglobulin test was negative, complement levels were reportedly low, and a low titer of cold agglutinins was present. Testing for antibodies against β2-glycoprotein I and cardiolipin was negative, as was a screening test for lupus anticoagulant. Nucleic acid amplification testing for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and other common respiratory viruses was negative. Flow cytometry of the peripheral blood revealed no aberrant clonal population of cells and no evidence of paroxysmal nocturnal hemoglobinuria.
Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, showed bilateral mediastinal and hilar lymphadenopathy that was unchanged from that observed on imaging performed 2 years earlier. Packed red cells were transfused, and the patient was admitted to the other hospital. Treatment with glucocorticoids was initiated for a working diagnosis of Coombs’-negative autoimmune hemolytic anemia.
On the third hospital day, anemia persisted, and additional units of packed red cells were transfused. The blood pressure had increased from 118/62 mm Hg on admission to 150/60 mm Hg. Treatment with glucocorticoids was stopped, and treatment with captopril was initiated for a working diagnosis of scleroderma renal crisis. Blood testing for the level of ADAMTS13 activity was performed, and on the sixth hospital day, treatment with plasmapheresis was started for the possible diagnosis of thrombotic thrombocytopenic purpura (TTP). The patient underwent a total of six sessions of plasmapheresis during the first 2 weeks of the hospitalization.
During the second week of the hospitalization, treatment with eculizumab was initiated. The patient received packed red-cell transfusions every 2 or 3 days for ongoing hemolytic anemia. The results of the blood test for activity of ADAMTS13 returned; the activity level was 65% (reference value, >67%), and treatment with plasmapheresis was stopped.
During the third week of the hospitalization, treatment with eculizumab was continued, and treatment with rituximab was initiated; however, the patient still received packed red-cell transfusions every 2 or 3 days. During the fourth week of the hospitalization, weekly treatment with both eculizumab and rituximab was continued, and a 3-day course of intravenous immune globulin was administered. Despite this treatment, there was no reduction in hemolysis.
During the fifth week of the hospitalization, the patient continued to receive packed red-cell transfusions every 2 or 3 days, and thrombocytopenia developed. Treatment with glucocorticoids was resumed, and treatment with twice-weekly injections of epoetin alfa was initiated. A biopsy specimen of the bone marrow reportedly showed hypercellular marrow with maturing trilineage hematopoiesis and erythroid predominance.
During the sixth week of the hospitalization, the need for red-cell transfusion persisted, treatment with cyclophosphamide was initiated, and the dose of captopril was increased. During the seventh week of the hospitalization, acute kidney injury (AKI) developed, and treatment with captopril and glucocorticoids was stopped. On the 50th hospital day, the patient was transferred to this hospital for further evaluation.
On evaluation at this hospital, the patient reported nausea, poor appetite, and weight loss of 9 kg during the past 2 months. She also reported that her urine had appeared pink or cola-colored after each transfusion of packed red cells.
Twenty-one years earlier, localized clinical stage T1cpN1aM0 (according to the tumor–node–metastasis classification system), estrogen receptor (ER)–positive, human epidermal growth factor receptor 2–negative invasive lobular breast cancer of the left breast was diagnosed. She had been treated initially with lumpectomy, radiation, and adjuvant chemotherapy, as well as with tamoxifen for 5 years and letrozole for 2 years. Three years before the current admission, there was a locoregional recurrence of ER-positive breast cancer in her left axilla; a lymph-node biopsy was negative. Staging studies reportedly revealed mildly prominent mediastinal and hilar lymph nodes and several indeterminate hepatic and renal lesions. Biopsy of the mediastinal and hilar lymph nodes was reportedly negative. The patient declined recommended chemotherapeutic treatment options for recurrent breast cancer and instead opted for surveillance imaging. Findings on magnetic resonance imaging, ultrasonography, and mammography of the breasts, which had been performed 6 months before the current admission, were reportedly unchanged from previous imaging. She had not palpated any new breast lumps on self-examination.
Three years before the current admission, systemic sclerosis associated with antibodies against RNA polymerase III was diagnosed. Sclerosis was limited to the skin, and the patient had not received any specific treatment. Other medical history included Sjögren’s syndrome, gastroesophageal reflux disease, latent tuberculosis that had been diagnosed 30 years earlier and treated with isoniazid for 9 months, dyslipidemia, and osteoporosis. Medications included exemestane, goserelin, calcium, cholecalciferol, pantoprazole, and rosuvastatin. The patient took no over-the-counter remedies or supplements. She was allergic to trimethoprim–sulfamethoxazole, which had caused fever and hives. She drank alcohol rarely and did not use any other substances. She had smoked tobacco for 3 years but had quit 50 years before the current admission. The patient was married and lived with her husband in New England. She was retired from work in health care. Three of her sisters had had breast cancer in their seventh decades of life; there was no family history of hemolysis.
On examination, the temperature was 36.3°C, the blood pressure 162/98 mm Hg, the pulse 105 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 17. The patient was alert and oriented. There was jaundice and scleral icterus. She had a well-healed lumpectomy scar on the upper outer quadrant of the left breast. There was no cervical, supraclavicular, or axillary lymphadenopathy. Mild skin thickening was present on the hands and feet, with subtly reduced skin mobility of the forearms and legs. The remainder of the examination was normal.
The blood level of creatinine was 2.87 mg per deciliter (254 μmol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 μmol per liter]), and the blood urea nitrogen level was 62 mg per deciliter (22 mmol per liter; reference range, 8 to 25 mg per deciliter [3 to 9 mmol per liter]). Other laboratory test results are shown in Table 1. Urinalysis revealed 3+ blood and 2+ protein, without bilirubin, urobilinogen, glucose, ketones, leukocyte esterase, or nitrates; the specific gravity and pH were normal. Microscopic examination of the urinary sediment revealed 10 to 20 red cells per high-power field (reference range, 0 to 2) and 3 to 5 white cells per high-power field (reference value,  ), and there were muddy-brown casts without dysmorphic red cells. The total protein:creatinine ratio in a spot urine sample was 6.41 (reference value, <0.15). A peripheral-blood smear was obtained.
Figure 1.

Peripheral-Blood Specimens on Admission to This Hospital.
Dr. Robert Ta: The peripheral-blood smear (Figure 1) showed anisopoikilocytosis, 10 to 15 schistocytes per high-power field, teardrop cells, nucleated red cells, reticulocytes, and mature and left-shifted myeloid cells.
Dr. Porterfield: Additional imaging studies were obtained, and a diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 71-year-old woman was admitted to this hospital because of refractory hemolytic anemia.
The patient, who had recurrent breast cancer and diffuse cutaneous systemic sclerosis, had been in her usual state of health until 7 months before the current admission, when fatigue and dyspnea on exertion developed. She was reportedly evaluated by a cardiologist and a pulmonologist, but no cause for her symptoms was identified.
Table 1.

Laboratory Data.
Two months before the current admission, dyspnea on exertion worsened, palpitations and dizziness developed, and the patient presented to another hospital for evaluation. Laboratory studies revealed anemia, a low blood level of haptoglobin, and an elevated blood level of lactate dehydrogenase. The blood levels of electrolytes were normal, as were the results of kidney-function tests; other laboratory test results are shown in Table 1. A peripheral-blood smear showed schistocytes. A direct antiglobulin test was negative, complement levels were reportedly low, and a low titer of cold agglutinins was present. Testing for antibodies against β2-glycoprotein I and cardiolipin was negative, as was a screening test for lupus anticoagulant. Nucleic acid amplification testing for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and other common respiratory viruses was negative. Flow cytometry of the peripheral blood revealed no aberrant clonal population of cells and no evidence of paroxysmal nocturnal hemoglobinuria.
Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, showed bilateral mediastinal and hilar lymphadenopathy that was unchanged from that observed on imaging performed 2 years earlier. Packed red cells were transfused, and the patient was admitted to the other hospital. Treatment with glucocorticoids was initiated for a working diagnosis of Coombs’-negative autoimmune hemolytic anemia.
On the third hospital day, anemia persisted, and additional units of packed red cells were transfused. The blood pressure had increased from 118/62 mm Hg on admission to 150/60 mm Hg. Treatment with glucocorticoids was stopped, and treatment with captopril was initiated for a working diagnosis of scleroderma renal crisis. Blood testing for the level of ADAMTS13 activity was performed, and on the sixth hospital day, treatment with plasmapheresis was started for the possible diagnosis of thrombotic thrombocytopenic purpura (TTP). The patient underwent a total of six sessions of plasmapheresis during the first 2 weeks of the hospitalization.
During the second week of the hospitalization, treatment with eculizumab was initiated. The patient received packed red-cell transfusions every 2 or 3 days for ongoing hemolytic anemia. The results of the blood test for activity of ADAMTS13 returned; the activity level was 65% (reference value, >67%), and treatment with plasmapheresis was stopped.
During the third week of the hospitalization, treatment with eculizumab was continued, and treatment with rituximab was initiated; however, the patient still received packed red-cell transfusions every 2 or 3 days. During the fourth week of the hospitalization, weekly treatment with both eculizumab and rituximab was continued, and a 3-day course of intravenous immune globulin was administered. Despite this treatment, there was no reduction in hemolysis.
During the fifth week of the hospitalization, the patient continued to receive packed red-cell transfusions every 2 or 3 days, and thrombocytopenia developed. Treatment with glucocorticoids was resumed, and treatment with twice-weekly injections of epoetin alfa was initiated. A biopsy specimen of the bone marrow reportedly showed hypercellular marrow with maturing trilineage hematopoiesis and erythroid predominance.
During the sixth week of the hospitalization, the need for red-cell transfusion persisted, treatment with cyclophosphamide was initiated, and the dose of captopril was increased. During the seventh week of the hospitalization, acute kidney injury (AKI) developed, and treatment with captopril and glucocorticoids was stopped. On the 50th hospital day, the patient was transferred to this hospital for further evaluation.
On evaluation at this hospital, the patient reported nausea, poor appetite, and weight loss of 9 kg during the past 2 months. She also reported that her urine had appeared pink or cola-colored after each transfusion of packed red cells.
Twenty-one years earlier, localized clinical stage T1cpN1aM0 (according to the tumor–node–metastasis classification system), estrogen receptor (ER)–positive, human epidermal growth factor receptor 2–negative invasive lobular breast cancer of the left breast was diagnosed. She had been treated initially with lumpectomy, radiation, and adjuvant chemotherapy, as well as with tamoxifen for 5 years and letrozole for 2 years. Three years before the current admission, there was a locoregional recurrence of ER-positive breast cancer in her left axilla; a lymph-node biopsy was negative. Staging studies reportedly revealed mildly prominent mediastinal and hilar lymph nodes and several indeterminate hepatic and renal lesions. Biopsy of the mediastinal and hilar lymph nodes was reportedly negative. The patient declined recommended chemotherapeutic treatment options for recurrent breast cancer and instead opted for surveillance imaging. Findings on magnetic resonance imaging, ultrasonography, and mammography of the breasts, which had been performed 6 months before the current admission, were reportedly unchanged from previous imaging. She had not palpated any new breast lumps on self-examination.
Three years before the current admission, systemic sclerosis associated with antibodies against RNA polymerase III was diagnosed. Sclerosis was limited to the skin, and the patient had not received any specific treatment. Other medical history included Sjögren’s syndrome, gastroesophageal reflux disease, latent tuberculosis that had been diagnosed 30 years earlier and treated with isoniazid for 9 months, dyslipidemia, and osteoporosis. Medications included exemestane, goserelin, calcium, cholecalciferol, pantoprazole, and rosuvastatin. The patient took no over-the-counter remedies or supplements. She was allergic to trimethoprim–sulfamethoxazole, which had caused fever and hives. She drank alcohol rarely and did not use any other substances. She had smoked tobacco for 3 years but had quit 50 years before the current admission. The patient was married and lived with her husband in New England. She was retired from work in health care. Three of her sisters had had breast cancer in their seventh decades of life; there was no family history of hemolysis.
On examination, the temperature was 36.3°C, the blood pressure 162/98 mm Hg, the pulse 105 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 17. The patient was alert and oriented. There was jaundice and scleral icterus. She had a well-healed lumpectomy scar on the upper outer quadrant of the left breast. There was no cervical, supraclavicular, or axillary lymphadenopathy. Mild skin thickening was present on the hands and feet, with subtly reduced skin mobility of the forearms and legs. The remainder of the examination was normal.
The blood level of creatinine was 2.87 mg per deciliter (254 μmol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 μmol per liter]), and the blood urea nitrogen level was 62 mg per deciliter (22 mmol per liter; reference range, 8 to 25 mg per deciliter [3 to 9 mmol per liter]). Other laboratory test results are shown in Table 1. Urinalysis revealed 3+ blood and 2+ protein, without bilirubin, urobilinogen, glucose, ketones, leukocyte esterase, or nitrates; the specific gravity and pH were normal. Microscopic examination of the urinary sediment revealed 10 to 20 red cells per high-power field (reference range, 0 to 2) and 3 to 5 white cells per high-power field (reference value,  ), and there were muddy-brown casts without dysmorphic red cells. The total protein:creatinine ratio in a spot urine sample was 6.41 (reference value, <0.15). A peripheral-blood smear was obtained.
Figure 1.

Peripheral-Blood Specimens on Admission to This Hospital.
Dr. Robert Ta: The peripheral-blood smear (Figure 1) showed anisopoikilocytosis, 10 to 15 schistocytes per high-power field, teardrop cells, nucleated red cells, reticulocytes, and mature and left-shifted myeloid cells.
Dr. Porterfield: Additional imaging studies were obtained, and a diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Atypical Hemolytic Uremic Syndrome (aHUS). The patient presents with refractory hemolytic anemia, thrombocytopenia, and acute kidney injury, which are the classic triad of symptoms for Hemolytic Uremic Syndrome (HUS). The presence of schistocytes on peripheral blood smear and elevated lactate dehydrogenase further support intravascular hemolysis. The negative Coombs test and low ADAMTS13 activity rule out autoimmune hemolytic anemia and thrombotic thrombocytopenic purpura, respectively. The lack of recent diarrheal illness and negative infectious workup make typical, Shiga-toxin mediated HUS unlikely. Therefore, the diagnosis of atypical HUS, which is not associated with Shiga toxin, is most likely.""
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        ""content"": ""Atypical Hemolytic Uremic Syndrome (aHUS)\nThe patient presents with refractory hemolytic anemia, thrombocytopenia, and acute kidney injury, which are the classic triad of symptoms for hemolytic uremic syndrome (HUS). The presence of schistocytes on peripheral blood smear and elevated lactate dehydrogenase further support intravascular hemolysis. The negative Coombs test rules out autoimmune hemolytic anemia. The normal ADAMTS13 activity level rules out thrombotic thrombocytopenic purpura (TTP). The lack of recent diarrheal illness and negative test for Shiga toxin-producing E. coli make typical HUS unlikely. The patient's age and the subacute onset of symptoms suggest atypical HUS (aHUS), which is often caused by uncontrolled activation of the alternative complement pathway. The patient's systemic sclerosis and breast cancer may have triggered aHUS, as it can be precipitated by systemic diseases and malignancies.""
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        ""content"": ""The patient is a 71-year-old woman with a history of recurrent breast cancer and diffuse cutaneous systemic sclerosis presenting with refractory hemolytic anemia. The differential diagnosis for this patient includes autoimmune hemolytic anemia, thrombotic thrombocytopenic purpura (TTP), paroxysmal nocturnal hemoglobinuria, and scleroderma renal crisis. The patient's peripheral blood smear showed schistocytes, which are fragmented red blood cells, indicative of microangiopathic hemolytic anemia. This finding is consistent with conditions such as TTP and hemolytic uremic syndrome (HUS). However, the patient's ADAMTS13 activity level was normal, which makes TTP less likely. The patient also had no evidence of paroxysmal nocturnal hemoglobinuria on flow cytometry. The patient's history of systemic sclerosis and the development of acute kidney injury (AKI) and hypertension suggest scleroderma renal crisis. However, the presence of schistocytes and the refractory nature of the anemia are not typical for this condition. The patient's anemia did not respond to treatment with glucocorticoids, rituximab, eculizumab, or cyclophosphamide, which would be unusual for autoimmune hemolytic anemia. The patient also developed thrombocytopenia and had evidence of hemolysis (low haptoglobin, high lactate dehydrogenase), which is more consistent with a microangiopathic process. The patient's urinalysis showed proteinuria and hematuria, and her urine protein:creatinine ratio was elevated, indicating kidney damage. The presence of muddy-brown casts in the urine is indicative of acute tubular necrosis, which is a common cause of AKI. Given the patient's history of cancer, the presence of schistocytes on peripheral smear, and the refractory nature of the anemia, a paraneoplastic microangiopathic hemolytic anemia associated with malignancy is a possibility.\n\nDiagnosis: Paraneoplastic microangiopathic hemolytic anemia associated with malignancy.""
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10.1056/NEJMcpc2211369,"Case 7-2023: A 70-Year-Old Man with Covid-19, Respiratory Failure, and Rashes","Hemoglobin (g/dl)	 	13.8	10.1	7.7
Hematocrit (%)	 	41.5	29.8	24.0
White-cell count (per μl)	 	320	9520	3250
Differential count (per μl)				
Neutrophils	 	50	8580	3050
Lymphocytes	 	60	80	30
Monocytes	 	110	580	80
Eosinophils	 	—	0	80
Platelet count (per μl)	 	168,000	106,000	35,000
Sodium (mmol/liter)	 	132	134	138
Potassium (mmol/liter)	 	3.1	4.8	4.9
Chloride (mmol/liter)	 	95	101	103
Carbon dioxide (mmol/liter)	 	19	18	18
Urea nitrogen (mg/dl)	 	67	31	20
Creatinine (mg/dl)	 	4.08	1.63	1.02
Glucose (mg/dl)	 	83	170	161",Mucormycosis.,Mucormycosis,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old man with a history of kidney transplantation was evaluated at this hospital because of multiple erythematous rashes that had developed during an admission for respiratory failure, pneumococcal bacteremia, and kidney failure.
Approximately 4.5 years before the current admission, the patient received a diagnosis of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis after he presented with progressive glomerulonephritis with kidney failure and new hemoptysis. The anti-myeloperoxidase antibody titer was 221.0 U (reference value, <2.8). The patient underwent plasmapheresis, and cyclophosphamide and prednisone were administered. Hemodialysis was initiated. Two weeks later, rituximab was administered, and cyclophosphamide and prednisone were discontinued. During the next 4 years, his renal function did not improve, and treatment with rituximab and hemodialysis was continued.
Four months before the current admission, the patient underwent transplantation of a kidney from a deceased donor with hepatitis C virus antibody–positive status. After the kidney transplantation, immunosuppressive therapy included a dose of basiliximab, mycophenolate mofetil, tacrolimus, and tapering doses of prednisone. The patient had delayed graft function; the blood creatinine level decreased from approximately 4.00 mg per deciliter (354 mmol per liter) immediately after transplantation to 1.50 mg per deciliter (133 mmol per liter) 6 weeks later. Six days before the current admission, at a routine follow-up visit, the creatinine level was 1.33 mg per deciliter (118 mmol per liter).
Four days before the current admission, the patient began to have central abdominal discomfort, nausea, anorexia, chills, and diarrhea with loose stools three times per day. During the next several days, he noticed decreased urine output and malaise, and he began to have rhinorrhea, cough, sinus congestion, and dyspnea. He was brought to the emergency department of this hospital.
A review of systems was notable for palpitations and dizziness and was negative for fever, emesis, and hematuria. The patient’s brother had recently received a diagnosis of coronavirus disease 2019 (Covid-19). The patient’s medical history was notable for vasculitis with end-stage kidney disease (culminating in kidney transplantation), coronary artery disease (with placement of a stent in the right coronary artery), atrial fibrillation, type 2 diabetes mellitus, hypertension, cholelithiasis (with cholecystectomy), colonic polyps and diverticulosis, gout, gastroesophageal reflux disease, hypothyroidism, sleep apnea, hernia (with hernia repair), and spinal stenosis. Medications taken at home included mycophenolate mofetil, tacrolimus, prednisone, trimethoprim–sulfamethoxazole, valganciclovir, warfarin, aspirin, atorvastatin, levothyroxine, and cholecalciferol, as well as lorazepam as needed. Penicillin had caused anaphylaxis.
The patient was a retired business owner and lived with family in Boston. He had a remote history of tobacco smoking that totaled 10 pack-years; he had quit smoking approximately 40 years earlier. He did not drink alcohol or use other substances. His family history was notable for diabetes, hypertension, and coronary artery disease in his father and siblings. There was no known family history of kidney or autoimmune disease.
The temperature was 36.4°C, the heart rate 130 beats per minute, the blood pressure 109/56 mm Hg, and the respiratory rate 24 breaths per minute. The oxygen saturation was 84% while the patient was breathing ambient air, 92% while he was receiving oxygen through a nasal cannula at a rate of 6 liters per minute, and 100% while he was receiving oxygen through a high-flow nasal cannula at a rate of 60 liters per minute. On examination, he appeared acutely ill and weak. He had bitemporal cachexia, dry oral mucosa, and increased work of breathing. Auscultation of the chest revealed tachypnea, diminished breath sounds and crackles in the lungs, and tachycardia. There was tenderness in the periumbilical area and the right lower quadrant, at the site of the kidney transplantation; the incision was well healed.
Table 1.

Laboratory Data.
Blood levels of lipase, calcium, magnesium, and phosphorus were normal; other laboratory test results are shown in Table 1. Blood and urine specimens were obtained for culture. An electrocardiogram showed possible sinus tachycardia with right bundle-branch block. Vancomycin and cefepime were administered intravenously. Three hours after presentation, a test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was positive, and remdesivir and dexamethasone were administered intravenously.
Figure 1.

Imaging Studies.
Dr. Joseph D. King: Radiography of the chest (Figure 1A) revealed confluent basilar consolidation in the left lung and scattered patchy opacities in the right lung. Ultrasonography that targeted the renal allograft revealed normal renal parenchyma and a trace amount of adjacent free fluid. Doppler ultrasonography (Figure 1B through 1E) showed patent vasculature with normal flow velocities but showed elevated renal arterial resistive indexes, which are suggestive of allograft dysfunction. Computed tomography (CT) of the chest (Figure 1F and 1G), performed without the administration of intravenous contrast material, revealed confluent consolidation in the lower lobes of both lungs, with more extensive findings in the left lung than in the right lung, as well as patchy multifocal consolidative and ground-glass opacities in the upper lobes of both lungs and the middle lobe of the right lung. Concurrent CT of the abdomen and pelvis (Figure 1H), performed without the administration of intravenous contrast material, was remarkable for only a trace amount of free fluid in the right lower quadrant, along the renal allograft.
Dr. Geadas: The patient was admitted to the medical intensive care unit (ICU) of this hospital. Phenylephrine was administered intravenously. He could not be weaned from the high-flow nasal cannula; because he had increased work of breathing and tachypnea, tracheal intubation was performed and mechanical ventilation initiated. Bronchoscopy revealed dark secretions in the lower lobe and lingula of the left lung. Blood cultures were positive for Streptococcus pneumoniae in four of four bottles. A blood test for cytomegalovirus (CMV) DNA and a urine test for legionella antigen were negative, and serum levels of 1,3-β-d-glucan and galactomannan were undetectable. Azithromycin, cefepime, linezolid, amiodarone, furosemide, and vitamin K were administered intravenously, and valganciclovir and atovaquone were administered orally. A transthoracic echocardiogram showed low-normal ventricular function, atrial enlargement, and no valvular vegetations. Continuous venovenous hemofiltration was initiated. ANCA titers were undetectable.
Figure 2.

Clinical Photographs.
On hospital day 3, excoriation and erythema of the buttock and a purpuric plaque on the sacrum were noted (Figure 2A). Repeat CT of the chest, abdomen, and pelvis showed no changes. Punch biopsy of skin on the right buttock was performed. The antibiotic regimen was transitioned to intravenous ceftriaxone.
The following day, histologic examination of the skin-biopsy specimen revealed epidermal necrosis, with scattered apoptotic and necrotic keratinocytes and extravasated erythrocytes. No microorganisms were identified, and microbiologic culture of the biopsy specimen was negative. Laboratory test results obtained on hospital day 4 are shown in Table 1.
During the next 6 days, treatment with continuous venovenous hemofiltration and intravenous ceftriaxone was continued. The level of mechanical ventilation was reduced from mandatory provided breaths to spontaneous ventilation, and the mode was switched to pressure-support ventilation. Repeat blood cultures were negative. On hospital day 11, the patient’s respiratory status worsened; the fraction of inspired oxygen was increased, and a mandatory respiratory rate was reinstituted.
Two days later, a new well-circumscribed purpuric patch was noted on the abdomen (Figure 2B). The patch measured 5 cm in greatest dimension and had a hyperpigmented halo but had no fluctuance or crepitus. The next day, a similar-appearing lesion was noted on the right thigh. Laboratory test results obtained on hospital day 14 are shown in Table 1.
Dr. King: Repeat CT of the chest, abdomen, and pelvis showed increased consolidative and ground-glass opacities in both lungs.
Dr. Geadas: Ceftriaxone was discontinued, and vancomycin, cefepime, and liposomal amphotericin B were administered intravenously. A diagnosis and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old man with a history of kidney transplantation was evaluated at this hospital because of multiple erythematous rashes that had developed during an admission for respiratory failure, pneumococcal bacteremia, and kidney failure.
Approximately 4.5 years before the current admission, the patient received a diagnosis of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis after he presented with progressive glomerulonephritis with kidney failure and new hemoptysis. The anti-myeloperoxidase antibody titer was 221.0 U (reference value, <2.8). The patient underwent plasmapheresis, and cyclophosphamide and prednisone were administered. Hemodialysis was initiated. Two weeks later, rituximab was administered, and cyclophosphamide and prednisone were discontinued. During the next 4 years, his renal function did not improve, and treatment with rituximab and hemodialysis was continued.
Four months before the current admission, the patient underwent transplantation of a kidney from a deceased donor with hepatitis C virus antibody–positive status. After the kidney transplantation, immunosuppressive therapy included a dose of basiliximab, mycophenolate mofetil, tacrolimus, and tapering doses of prednisone. The patient had delayed graft function; the blood creatinine level decreased from approximately 4.00 mg per deciliter (354 mmol per liter) immediately after transplantation to 1.50 mg per deciliter (133 mmol per liter) 6 weeks later. Six days before the current admission, at a routine follow-up visit, the creatinine level was 1.33 mg per deciliter (118 mmol per liter).
Four days before the current admission, the patient began to have central abdominal discomfort, nausea, anorexia, chills, and diarrhea with loose stools three times per day. During the next several days, he noticed decreased urine output and malaise, and he began to have rhinorrhea, cough, sinus congestion, and dyspnea. He was brought to the emergency department of this hospital.
A review of systems was notable for palpitations and dizziness and was negative for fever, emesis, and hematuria. The patient’s brother had recently received a diagnosis of coronavirus disease 2019 (Covid-19). The patient’s medical history was notable for vasculitis with end-stage kidney disease (culminating in kidney transplantation), coronary artery disease (with placement of a stent in the right coronary artery), atrial fibrillation, type 2 diabetes mellitus, hypertension, cholelithiasis (with cholecystectomy), colonic polyps and diverticulosis, gout, gastroesophageal reflux disease, hypothyroidism, sleep apnea, hernia (with hernia repair), and spinal stenosis. Medications taken at home included mycophenolate mofetil, tacrolimus, prednisone, trimethoprim–sulfamethoxazole, valganciclovir, warfarin, aspirin, atorvastatin, levothyroxine, and cholecalciferol, as well as lorazepam as needed. Penicillin had caused anaphylaxis.
The patient was a retired business owner and lived with family in Boston. He had a remote history of tobacco smoking that totaled 10 pack-years; he had quit smoking approximately 40 years earlier. He did not drink alcohol or use other substances. His family history was notable for diabetes, hypertension, and coronary artery disease in his father and siblings. There was no known family history of kidney or autoimmune disease.
The temperature was 36.4°C, the heart rate 130 beats per minute, the blood pressure 109/56 mm Hg, and the respiratory rate 24 breaths per minute. The oxygen saturation was 84% while the patient was breathing ambient air, 92% while he was receiving oxygen through a nasal cannula at a rate of 6 liters per minute, and 100% while he was receiving oxygen through a high-flow nasal cannula at a rate of 60 liters per minute. On examination, he appeared acutely ill and weak. He had bitemporal cachexia, dry oral mucosa, and increased work of breathing. Auscultation of the chest revealed tachypnea, diminished breath sounds and crackles in the lungs, and tachycardia. There was tenderness in the periumbilical area and the right lower quadrant, at the site of the kidney transplantation; the incision was well healed.
Table 1.

Laboratory Data.
Blood levels of lipase, calcium, magnesium, and phosphorus were normal; other laboratory test results are shown in Table 1. Blood and urine specimens were obtained for culture. An electrocardiogram showed possible sinus tachycardia with right bundle-branch block. Vancomycin and cefepime were administered intravenously. Three hours after presentation, a test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was positive, and remdesivir and dexamethasone were administered intravenously.
Figure 1.

Imaging Studies.
Dr. Joseph D. King: Radiography of the chest (Figure 1A) revealed confluent basilar consolidation in the left lung and scattered patchy opacities in the right lung. Ultrasonography that targeted the renal allograft revealed normal renal parenchyma and a trace amount of adjacent free fluid. Doppler ultrasonography (Figure 1B through 1E) showed patent vasculature with normal flow velocities but showed elevated renal arterial resistive indexes, which are suggestive of allograft dysfunction. Computed tomography (CT) of the chest (Figure 1F and 1G), performed without the administration of intravenous contrast material, revealed confluent consolidation in the lower lobes of both lungs, with more extensive findings in the left lung than in the right lung, as well as patchy multifocal consolidative and ground-glass opacities in the upper lobes of both lungs and the middle lobe of the right lung. Concurrent CT of the abdomen and pelvis (Figure 1H), performed without the administration of intravenous contrast material, was remarkable for only a trace amount of free fluid in the right lower quadrant, along the renal allograft.
Dr. Geadas: The patient was admitted to the medical intensive care unit (ICU) of this hospital. Phenylephrine was administered intravenously. He could not be weaned from the high-flow nasal cannula; because he had increased work of breathing and tachypnea, tracheal intubation was performed and mechanical ventilation initiated. Bronchoscopy revealed dark secretions in the lower lobe and lingula of the left lung. Blood cultures were positive for Streptococcus pneumoniae in four of four bottles. A blood test for cytomegalovirus (CMV) DNA and a urine test for legionella antigen were negative, and serum levels of 1,3-β-d-glucan and galactomannan were undetectable. Azithromycin, cefepime, linezolid, amiodarone, furosemide, and vitamin K were administered intravenously, and valganciclovir and atovaquone were administered orally. A transthoracic echocardiogram showed low-normal ventricular function, atrial enlargement, and no valvular vegetations. Continuous venovenous hemofiltration was initiated. ANCA titers were undetectable.
Figure 2.

Clinical Photographs.
On hospital day 3, excoriation and erythema of the buttock and a purpuric plaque on the sacrum were noted (Figure 2A). Repeat CT of the chest, abdomen, and pelvis showed no changes. Punch biopsy of skin on the right buttock was performed. The antibiotic regimen was transitioned to intravenous ceftriaxone.
The following day, histologic examination of the skin-biopsy specimen revealed epidermal necrosis, with scattered apoptotic and necrotic keratinocytes and extravasated erythrocytes. No microorganisms were identified, and microbiologic culture of the biopsy specimen was negative. Laboratory test results obtained on hospital day 4 are shown in Table 1.
During the next 6 days, treatment with continuous venovenous hemofiltration and intravenous ceftriaxone was continued. The level of mechanical ventilation was reduced from mandatory provided breaths to spontaneous ventilation, and the mode was switched to pressure-support ventilation. Repeat blood cultures were negative. On hospital day 11, the patient’s respiratory status worsened; the fraction of inspired oxygen was increased, and a mandatory respiratory rate was reinstituted.
Two days later, a new well-circumscribed purpuric patch was noted on the abdomen (Figure 2B). The patch measured 5 cm in greatest dimension and had a hyperpigmented halo but had no fluctuance or crepitus. The next day, a similar-appearing lesion was noted on the right thigh. Laboratory test results obtained on hospital day 14 are shown in Table 1.
Dr. King: Repeat CT of the chest, abdomen, and pelvis showed increased consolidative and ground-glass opacities in both lungs.
Dr. Geadas: Ceftriaxone was discontinued, and vancomycin, cefepime, and liposomal amphotericin B were administered intravenously. A diagnosis and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Ecthyma gangrenosum due to Pseudomonas aeruginosa septicemia. \n\nThe patient is immunosuppressed due to kidney transplantation and has developed multiple erythematous rashes. The description of the rashes as well-circumscribed purpuric patches with a hyperpigmented halo is characteristic of ecthyma gangrenosum, a skin infection often caused by Pseudomonas aeruginosa. The patient's history of recent hospitalization and respiratory failure could have exposed him to this pathogen. The patient's worsening respiratory status and the findings of increased consolidative and ground-glass opacities in both lungs on CT scan suggest a possible respiratory infection, which could be the source of a Pseudomonas aeruginosa bacteremia leading to the skin manifestations.""
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        ""content"": ""The patient is a 70-year-old man with a history of kidney transplantation, presenting with multiple erythematous rashes, respiratory failure, pneumococcal bacteremia, and kidney failure. The differential diagnosis for this patient includes bacterial sepsis, viral infection, drug reaction, and vasculitis. The patient's history of kidney transplantation and immunosuppressive therapy puts him at a higher risk for infections. His positive blood cultures for Streptococcus pneumoniae and symptoms of respiratory failure suggest bacterial sepsis. However, his positive test for SARS-CoV-2 RNA indicates a viral infection, specifically COVID-19, which could also explain his respiratory symptoms. The development of rashes could be a drug reaction, given the patient's extensive medication list. Finally, the patient's history of ANCA-associated vasculitis could suggest a flare of this condition, although his ANCA titers were undetectable. The presence of epidermal necrosis and necrotic keratinocytes in the skin biopsy, along with the absence of microorganisms, makes a drug reaction or vasculitis more likely than an infection. Given the patient's history of vasculitis, the development of new skin lesions despite antibiotic therapy, and the histological findings, a flare of ANCA-associated vasculitis seems most likely.\n\nDiagnosis: Flare of ANCA-associated vasculitis.""
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}",Flare of ANCA-associated vasculitis,N
10.1056/NEJMcpc2211368,Case 6-2023: A 68-Year-Old Man with Recurrent Strokes,,Paraneoplastic vasculitis of the central nervous system.,Recurrent subcortical infarcts with progressive leukoencephalopathy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old man was admitted to this hospital because of worsening confusion.
The patient had a history of hypertension and coronary artery disease. A myocardial infarction had occurred 18 years before the current admission; atrial fibrillation had also been diagnosed at that time. He had taken warfarin for many years but had stopped taking it 10 years before this admission.
Seven and a half weeks before the current admission, the patient presented to another hospital with aphasia. His score on the National Institutes of Health Stroke Scale was 3, with scores ranging from 0 to 42 and higher scores indicating greater severity. The score of 3 was due to partial loss of the right visual field and mild-to-moderate aphasia and dysarthria.
Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed no abnormalities. CT angiography of the head and neck revealed calcified atherosclerosis along the arch of the aorta, the origin of the left vertebral artery, the intracranial portion of the left vertebral artery, the carotid bifurcations, and the cavernous portions of both internal carotid arteries; there was no hemodynamically significant stenosis. Treatment with aspirin and clopidogrel was initiated. The patient was admitted to the hospital, and the aphasia resolved on the second hospital day.
Magnetic resonance imaging (MRI) of the head, performed without the administration of intravenous contrast material, revealed a few small foci of acute infarction involving the frontal lobes, the posterior limb of the right internal capsule, and the right middle cerebellar peduncle. There was also a small focus of remote petechial hemorrhage in the subcortical white matter of the left parietal lobe.
Although continuous telemetry revealed no evidence of atrial fibrillation, the patient’s strokes were thought to be cardioembolic, resulting from atrial fibrillation. Treatment with aspirin was continued, clopidogrel was discontinued, and apixaban was started; previously prescribed antihypertensive therapy with amlodipine and lisinopril was resumed. The patient was discharged home on the second hospital day.
Four days after discharge, and 7 weeks before the current admission, the patient presented to the other hospital with transient mild aphasia. Results of CT of the head (performed without the administration of intravenous contrast material) and MRI of the head (performed with and without the administration of intravenous contrast material) were reportedly unchanged from the studies obtained 6 days earlier. The patient’s systolic blood pressure was less than 100 mm Hg, and his symptoms were thought to be due to hypoperfusion or recrudescence of symptoms from previous stroke. Treatment with amlodipine and lisinopril was stopped, and the systolic blood pressure increased. The patient was discharged home on the fourth hospital day.
Three weeks after discharge, and 3.5 weeks before the current admission, the patient’s daughter noticed that the patient had confusion and lethargy, and she took him to the other hospital for evaluation. She reported that he had new urinary incontinence, unsteady gait, and withdrawn affect. MRI of the head, performed without the administration of intravenous contrast material, revealed new foci of acute infarction involving the centrum semiovale and corona radiata bilaterally.
Figure 1.

Initial Imaging Studies.
Dr. Javier M. Romero: CT of the chest (Figure 1A) revealed diffuse emphysematous changes, including a spiculated mass (1.7 cm in diameter) with perilesional rectilinear markings in the lower lobe of the left lung. CT of the abdomen (Figure 1B) revealed an exophytic hyperdense mass (1.6 cm in diameter) arising from the anterior cortex of the left kidney.
Dr. Silverman: On the fourth hospital day, the patient was transferred to a rehabilitation facility with plans for an oncology evaluation after discharge. After 10 days at the rehabilitation center, he was discharged home.
Three days after discharge from the rehabilitation center, and 1 week before the current admission, numbness and tingling in the right hand and forearm developed, and the patient’s daughter again took the patient to the other hospital. On examination, he had pronator drift of the right arm and dysmetria on finger-to-nose testing. MRI of the head revealed new foci of acute infarction involving the left thalamus, the subcortical white matter of the right frontal lobe, and the periventricular white matter on the left side, but there was no hemorrhage. Treatment with apixaban was stopped, and enoxaparin was started. The patient was discharged home on the third hospital day.
Five days after discharge, the patient’s daughter noticed that the patient had new difficulty with swallowing pills and worsening confusion, and she brought him to the emergency department of this hospital for evaluation. The patient was not able to provide additional history, but his daughter reported that his aphasia and difficulty with balance had worsened since discharge from the other hospital. Other medical history included hypertension, hyperlipidemia, diabetes mellitus, and obesity. Medications included enoxaparin, aspirin, atorvastatin, and metformin. There were no known drug allergies. The patient lived alone in a suburb of Boston and was retired. He had smoked cigarettes for 40 years, but he had recently decreased tobacco use from one pack per day to three cigarettes per day. He smoked marijuana occasionally, and he drank alcohol rarely. His father had had coronary artery disease with a myocardial infarction in the fourth decade of life.
The temporal temperature was 36.6°C, the blood pressure 158/75 mm Hg, the pulse 70 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.1. The patient was alert and interactive. He was able to answer orientation questions correctly, although he was slow to respond. His speech was fluent, with no paraphasic errors. He had some difficulty with following simple commands and was unable to follow complex commands. There was decreased activation of the right nasolabial fold with preserved wrinkling of the forehead. Pronator drift of the right arm was present, and there was mild hemiparesis on the right side. The remainder of the examination was normal.
Blood levels of electrolytes and rheumatoid factor were normal, as were results of liver-function and kidney-function tests. The hemoglobin level was 12.7 g per deciliter (reference range, 13.5 to 17.5); the remainder of the complete blood count with differential count was normal. The erythrocyte sedimentation rate was 15 mm per hour (reference range, 0 to 13). The d-dimer level was 912 ng per milliliter (reference value,  ). Urinalysis showed more than 100 white cells per high-power field (reference value,  ). A test for lupus anticoagulant was negative, as were tests for antibodies against cardiolipin and β2-glycoprotein 1. Antinuclear antibodies were present at a titer of 1:160 in a speckled pattern. Blood specimens were obtained for culture. Imaging studies were obtained.
Dr. Romero: CT angiography of the head and neck (Figure 1C), performed with and without the administration of intravenous contrast material, revealed focal encephalomalacia within the left frontal corona radiata and right cerebral peduncle. Atheromatous changes had resulted in multifocal mild narrowing of the cervical and intracranial arteries. MRI of the head (Figure 1D and 1E), performed without the administration of intravenous contrast material, revealed numerous new small foci of acute infarction involving the centrum semiovale and corona radiata bilaterally, the left thalamus, the left internal capsule and lentiform nucleus, the left subinsular region, the medial right precentral gyrus, the anterior right frontal lobe, the superior frontal gyri, and the right temporal lobe. There were also several scattered patches of increased signal intensity in the periventricular and subcortical white matter on fluid-attenuated inversion recovery imaging and T2-weighted imaging, findings that are indicative of moderate small-vessel disease.
Dr. Silverman: The patient was admitted to the hospital, and intravenous heparin was administered. Transthoracic echocardiography performed on the second hospital day revealed a normal ejection fraction and no valvular vegetations or patent foramen ovale. Blood cultures showed no growth. A diagnosis and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old man was admitted to this hospital because of worsening confusion.
The patient had a history of hypertension and coronary artery disease. A myocardial infarction had occurred 18 years before the current admission; atrial fibrillation had also been diagnosed at that time. He had taken warfarin for many years but had stopped taking it 10 years before this admission.
Seven and a half weeks before the current admission, the patient presented to another hospital with aphasia. His score on the National Institutes of Health Stroke Scale was 3, with scores ranging from 0 to 42 and higher scores indicating greater severity. The score of 3 was due to partial loss of the right visual field and mild-to-moderate aphasia and dysarthria.
Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed no abnormalities. CT angiography of the head and neck revealed calcified atherosclerosis along the arch of the aorta, the origin of the left vertebral artery, the intracranial portion of the left vertebral artery, the carotid bifurcations, and the cavernous portions of both internal carotid arteries; there was no hemodynamically significant stenosis. Treatment with aspirin and clopidogrel was initiated. The patient was admitted to the hospital, and the aphasia resolved on the second hospital day.
Magnetic resonance imaging (MRI) of the head, performed without the administration of intravenous contrast material, revealed a few small foci of acute infarction involving the frontal lobes, the posterior limb of the right internal capsule, and the right middle cerebellar peduncle. There was also a small focus of remote petechial hemorrhage in the subcortical white matter of the left parietal lobe.
Although continuous telemetry revealed no evidence of atrial fibrillation, the patient’s strokes were thought to be cardioembolic, resulting from atrial fibrillation. Treatment with aspirin was continued, clopidogrel was discontinued, and apixaban was started; previously prescribed antihypertensive therapy with amlodipine and lisinopril was resumed. The patient was discharged home on the second hospital day.
Four days after discharge, and 7 weeks before the current admission, the patient presented to the other hospital with transient mild aphasia. Results of CT of the head (performed without the administration of intravenous contrast material) and MRI of the head (performed with and without the administration of intravenous contrast material) were reportedly unchanged from the studies obtained 6 days earlier. The patient’s systolic blood pressure was less than 100 mm Hg, and his symptoms were thought to be due to hypoperfusion or recrudescence of symptoms from previous stroke. Treatment with amlodipine and lisinopril was stopped, and the systolic blood pressure increased. The patient was discharged home on the fourth hospital day.
Three weeks after discharge, and 3.5 weeks before the current admission, the patient’s daughter noticed that the patient had confusion and lethargy, and she took him to the other hospital for evaluation. She reported that he had new urinary incontinence, unsteady gait, and withdrawn affect. MRI of the head, performed without the administration of intravenous contrast material, revealed new foci of acute infarction involving the centrum semiovale and corona radiata bilaterally.
Figure 1.

Initial Imaging Studies.
Dr. Javier M. Romero: CT of the chest (Figure 1A) revealed diffuse emphysematous changes, including a spiculated mass (1.7 cm in diameter) with perilesional rectilinear markings in the lower lobe of the left lung. CT of the abdomen (Figure 1B) revealed an exophytic hyperdense mass (1.6 cm in diameter) arising from the anterior cortex of the left kidney.
Dr. Silverman: On the fourth hospital day, the patient was transferred to a rehabilitation facility with plans for an oncology evaluation after discharge. After 10 days at the rehabilitation center, he was discharged home.
Three days after discharge from the rehabilitation center, and 1 week before the current admission, numbness and tingling in the right hand and forearm developed, and the patient’s daughter again took the patient to the other hospital. On examination, he had pronator drift of the right arm and dysmetria on finger-to-nose testing. MRI of the head revealed new foci of acute infarction involving the left thalamus, the subcortical white matter of the right frontal lobe, and the periventricular white matter on the left side, but there was no hemorrhage. Treatment with apixaban was stopped, and enoxaparin was started. The patient was discharged home on the third hospital day.
Five days after discharge, the patient’s daughter noticed that the patient had new difficulty with swallowing pills and worsening confusion, and she brought him to the emergency department of this hospital for evaluation. The patient was not able to provide additional history, but his daughter reported that his aphasia and difficulty with balance had worsened since discharge from the other hospital. Other medical history included hypertension, hyperlipidemia, diabetes mellitus, and obesity. Medications included enoxaparin, aspirin, atorvastatin, and metformin. There were no known drug allergies. The patient lived alone in a suburb of Boston and was retired. He had smoked cigarettes for 40 years, but he had recently decreased tobacco use from one pack per day to three cigarettes per day. He smoked marijuana occasionally, and he drank alcohol rarely. His father had had coronary artery disease with a myocardial infarction in the fourth decade of life.
The temporal temperature was 36.6°C, the blood pressure 158/75 mm Hg, the pulse 70 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.1. The patient was alert and interactive. He was able to answer orientation questions correctly, although he was slow to respond. His speech was fluent, with no paraphasic errors. He had some difficulty with following simple commands and was unable to follow complex commands. There was decreased activation of the right nasolabial fold with preserved wrinkling of the forehead. Pronator drift of the right arm was present, and there was mild hemiparesis on the right side. The remainder of the examination was normal.
Blood levels of electrolytes and rheumatoid factor were normal, as were results of liver-function and kidney-function tests. The hemoglobin level was 12.7 g per deciliter (reference range, 13.5 to 17.5); the remainder of the complete blood count with differential count was normal. The erythrocyte sedimentation rate was 15 mm per hour (reference range, 0 to 13). The d-dimer level was 912 ng per milliliter (reference value,  ). Urinalysis showed more than 100 white cells per high-power field (reference value,  ). A test for lupus anticoagulant was negative, as were tests for antibodies against cardiolipin and β2-glycoprotein 1. Antinuclear antibodies were present at a titer of 1:160 in a speckled pattern. Blood specimens were obtained for culture. Imaging studies were obtained.
Dr. Romero: CT angiography of the head and neck (Figure 1C), performed with and without the administration of intravenous contrast material, revealed focal encephalomalacia within the left frontal corona radiata and right cerebral peduncle. Atheromatous changes had resulted in multifocal mild narrowing of the cervical and intracranial arteries. MRI of the head (Figure 1D and 1E), performed without the administration of intravenous contrast material, revealed numerous new small foci of acute infarction involving the centrum semiovale and corona radiata bilaterally, the left thalamus, the left internal capsule and lentiform nucleus, the left subinsular region, the medial right precentral gyrus, the anterior right frontal lobe, the superior frontal gyri, and the right temporal lobe. There were also several scattered patches of increased signal intensity in the periventricular and subcortical white matter on fluid-attenuated inversion recovery imaging and T2-weighted imaging, findings that are indicative of moderate small-vessel disease.
Dr. Silverman: The patient was admitted to the hospital, and intravenous heparin was administered. Transthoracic echocardiography performed on the second hospital day revealed a normal ejection fraction and no valvular vegetations or patent foramen ovale. Blood cultures showed no growth. A diagnosis and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 68-year-old man with a history of hypertension, coronary artery disease, and atrial fibrillation. He presents with worsening confusion, aphasia, and unsteady gait. He has had multiple episodes of acute infarction involving various parts of the brain. The differential diagnosis for this patient includes stroke, transient ischemic attack (TIA), brain tumor, and dementia. Given the patient's history of atrial fibrillation and the findings of multiple acute infarctions in different areas of the brain, a cardioembolic stroke is highly likely. The patient's symptoms of confusion and unsteady gait could also be due to a brain tumor. However, the imaging studies do not show any evidence of a mass or lesion in the brain, making this diagnosis less likely. Dementia could also present with confusion and unsteady gait. However, the acute onset and fluctuating course of the patient's symptoms, along with the findings of acute infarctions on imaging, are not typical for dementia. A TIA could also cause the patient's symptoms. However, TIAs are usually transient and do not cause lasting neurological deficits. The patient's symptoms have been persistent and have even worsened over time, making a TIA less likely. Given the patient's history and the findings on imaging, the most likely diagnosis is recurrent cardioembolic strokes due to atrial fibrillation.\n\nDiagnosis: Recurrent cardioembolic strokes due to atrial fibrillation.""
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}",Recurrent cardioembolic strokes due to atrial fibrillation,Y
10.1056/NEJMcpc2211364,"Case 5-2023: A 67-Year-Old Man with Interstitial Lung Disease, Fever, and Myalgias","Hematocrit (%)	 	43.0	39.1
Hemoglobin (g/dl)	 	14.0	12.7
White-cell count (per μl)	 	5770	3040
Differential count (per μl)			
Neutrophils	 	4860	2800
Lymphocytes	 	210	160
Monocytes	 	570	30
Eosinophils	 	0	50
Basophils	 00	50	0
Bands	0–100	80	0
Platelet count (per μl)	 	225,000	59,000
Alkaline phosphatase (U/liter)	 	109	167
Alanine aminotransferase (U/liter)	 	48	76
Aspartate aminotransferase (U/liter)	 	61	115
Total bilirubin (mg/dl)	0.0–1.0	0.4	0.4
Direct bilirubin (mg/dl)	0. 	<0.2	<0.2
Albumin (g/dl)	 	4.0	4.0",Human granulocytic anaplasmosis.,Anaplasmosis,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 67-year-old man was admitted to this hospital because of fever, myalgias, and one previous episode of vomiting.
Nine months before this admission, the patient was admitted to another hospital with cough and shortness of breath, and coronavirus disease 2019 (Covid-19) pneumonia was diagnosed. He received remdesivir, dexamethasone, and supplemental oxygen, which was delivered through a high-flow nasal cannula. His clinical condition gradually improved, and he was discharged home with supplemental oxygen, which was to be administered through a nasal cannula at a rate of 4 liters per minute.
While the patient was recovering at home, cough persisted and shortness of breath worsened, despite treatment with prednisone. Two weeks after discharge from the hospital, organizing pneumonia was diagnosed. Pulmonary-function testing revealed a severe restrictive ventilatory defect with impaired gas exchange, and findings on computed tomography (CT) of the chest were consistent with organizing pneumonia superimposed on fibrotic interstitial lung disease. Treatment with pirfenidone and mycophenolate mofetil was initiated, and the dose of prednisone was increased. Despite the use of these treatments, there was no decrease in dyspnea; consequently, treatment with pirfenidone was stopped, and the dose of prednisone was tapered over the course of the 2 months before the current admission. Because of persistent severe dyspnea on exertion, the patient was listed for lung transplantation 2 weeks before the current admission.
Two days before the current admission, myalgias and nausea developed, and an episode of vomiting occurred. The tympanic temperature, as measured by the patient at home, was 40.0°C. There was also a slight increase in shortness of breath, and the patient began to administer supplemental oxygen at an increased rate of 5 liters per minute. One day before the current admission, a home test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen was negative. The patient presented to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported a chronic dry cough that was unchanged. Other medical history included gastroesophageal reflux disease, obstructive sleep apnea, and prostate cancer that had been treated surgically 4 years before this admission. Medications included albuterol, calcium carbonate, cholecalciferol, ipratropium–albuterol delivered by nebulizer, mycophenolate mofetil, pantoprazole, prednisone, and trimethoprim–sulfamethoxazole. He had no known drug allergies. He drank three or four alcoholic drinks per week and was a lifelong nonsmoker. He lived in a rural area of New England on five acres of land with woods. He used well water at home, but he boiled drinking water before consumption. He owned a dog, and he spent time outdoors, including mowing the lawn 1 week before this admission. He had had mosquito bites but no known tick bites. He was retired from previous work as a welder.
Table 1.

Laboratory Data.
On examination, the temporal temperature was 36.6°C, the blood pressure 126/67 mm Hg, the pulse 91 beats per minute, the respiratory rate 28 breaths per minute, and the oxygen saturation 97% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 5 liters per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.8. Respirations were slightly labored, and the patient spoke in short sentences. He was alert and oriented and answered questions appropriately. No oral thrush was present. There were crackles at the bases of both lung fields. There was no hepatosplenomegaly. The remainder of the examination was normal. The blood levels of electrolytes and glucose were normal, as were the results of kidney-function tests. Urinalysis results were normal. The blood level of 1,3-β-d-glucan was less than 31 pg per milliliter (reference value, <60), and the blood galactomannan index was 0.13 (reference range, 0.00 to 0.49). Tests for Lyme disease and human immunodeficiency virus (HIV) were negative; other laboratory test results are shown in Table 1. A respiratory viral panel that included testing for SARS-CoV-2 nucleic acids was negative. Imaging studies were obtained.
Figure 1.

CT of the Chest on Admission.
Dr. Amita Sharma: Chest radiography revealed bilateral peripheral reticular opacities that were similar in appearance to those observed in studies obtained 7 and 9 months earlier and were consistent with the patient’s reported history of interstitial lung disease, with no new focal consolidation. CT of the chest (Figure 1), performed without the administration of intravenous contrast material, showed resolution of multifocal air-space opacities and new peripheral curvilinear opacity. There was peripheral reticulation that was unchanged from that seen in the studies obtained 7 and 9 months earlier, basilar-predominant architectural distortion, and traction bronchiectasis with evidence of honeycombing in the lung bases. There was a slight decrease in mediastinal lymphadenopathy as compared with the earlier studies and a single new paraesophageal lymph node on the right side.
Dr. Croughan: Blood and urine cultures were obtained, and treatment with intravenous cefepime was initiated. Twelve hours after the patient presented to the emergency department, the temporal temperature was 38.8°C, the blood pressure 82/53 mm Hg, the pulse 78 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 5 liters per minute. One liter of intravenous fluids was administered, and the blood pressure increased to 108/52 mm Hg. Owing to the patient’s acute illness, the dose of prednisone was increased, and he was admitted to the hospital.
On hospital day 1, fever persisted; the maximum temporal temperature was 39.9°C. The blood pressure remained stable; treatment with intravenous vancomycin was added.
On hospital day 2, pancytopenia developed, and the results of liver-function tests had worsened; laboratory test results are shown in Table 1. Blood and urine cultures showed no growth. A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 67-year-old man was admitted to this hospital because of fever, myalgias, and one previous episode of vomiting.
Nine months before this admission, the patient was admitted to another hospital with cough and shortness of breath, and coronavirus disease 2019 (Covid-19) pneumonia was diagnosed. He received remdesivir, dexamethasone, and supplemental oxygen, which was delivered through a high-flow nasal cannula. His clinical condition gradually improved, and he was discharged home with supplemental oxygen, which was to be administered through a nasal cannula at a rate of 4 liters per minute.
While the patient was recovering at home, cough persisted and shortness of breath worsened, despite treatment with prednisone. Two weeks after discharge from the hospital, organizing pneumonia was diagnosed. Pulmonary-function testing revealed a severe restrictive ventilatory defect with impaired gas exchange, and findings on computed tomography (CT) of the chest were consistent with organizing pneumonia superimposed on fibrotic interstitial lung disease. Treatment with pirfenidone and mycophenolate mofetil was initiated, and the dose of prednisone was increased. Despite the use of these treatments, there was no decrease in dyspnea; consequently, treatment with pirfenidone was stopped, and the dose of prednisone was tapered over the course of the 2 months before the current admission. Because of persistent severe dyspnea on exertion, the patient was listed for lung transplantation 2 weeks before the current admission.
Two days before the current admission, myalgias and nausea developed, and an episode of vomiting occurred. The tympanic temperature, as measured by the patient at home, was 40.0°C. There was also a slight increase in shortness of breath, and the patient began to administer supplemental oxygen at an increased rate of 5 liters per minute. One day before the current admission, a home test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen was negative. The patient presented to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported a chronic dry cough that was unchanged. Other medical history included gastroesophageal reflux disease, obstructive sleep apnea, and prostate cancer that had been treated surgically 4 years before this admission. Medications included albuterol, calcium carbonate, cholecalciferol, ipratropium–albuterol delivered by nebulizer, mycophenolate mofetil, pantoprazole, prednisone, and trimethoprim–sulfamethoxazole. He had no known drug allergies. He drank three or four alcoholic drinks per week and was a lifelong nonsmoker. He lived in a rural area of New England on five acres of land with woods. He used well water at home, but he boiled drinking water before consumption. He owned a dog, and he spent time outdoors, including mowing the lawn 1 week before this admission. He had had mosquito bites but no known tick bites. He was retired from previous work as a welder.
Table 1.

Laboratory Data.
On examination, the temporal temperature was 36.6°C, the blood pressure 126/67 mm Hg, the pulse 91 beats per minute, the respiratory rate 28 breaths per minute, and the oxygen saturation 97% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 5 liters per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.8. Respirations were slightly labored, and the patient spoke in short sentences. He was alert and oriented and answered questions appropriately. No oral thrush was present. There were crackles at the bases of both lung fields. There was no hepatosplenomegaly. The remainder of the examination was normal. The blood levels of electrolytes and glucose were normal, as were the results of kidney-function tests. Urinalysis results were normal. The blood level of 1,3-β-d-glucan was less than 31 pg per milliliter (reference value, <60), and the blood galactomannan index was 0.13 (reference range, 0.00 to 0.49). Tests for Lyme disease and human immunodeficiency virus (HIV) were negative; other laboratory test results are shown in Table 1. A respiratory viral panel that included testing for SARS-CoV-2 nucleic acids was negative. Imaging studies were obtained.
Figure 1.

CT of the Chest on Admission.
Dr. Amita Sharma: Chest radiography revealed bilateral peripheral reticular opacities that were similar in appearance to those observed in studies obtained 7 and 9 months earlier and were consistent with the patient’s reported history of interstitial lung disease, with no new focal consolidation. CT of the chest (Figure 1), performed without the administration of intravenous contrast material, showed resolution of multifocal air-space opacities and new peripheral curvilinear opacity. There was peripheral reticulation that was unchanged from that seen in the studies obtained 7 and 9 months earlier, basilar-predominant architectural distortion, and traction bronchiectasis with evidence of honeycombing in the lung bases. There was a slight decrease in mediastinal lymphadenopathy as compared with the earlier studies and a single new paraesophageal lymph node on the right side.
Dr. Croughan: Blood and urine cultures were obtained, and treatment with intravenous cefepime was initiated. Twelve hours after the patient presented to the emergency department, the temporal temperature was 38.8°C, the blood pressure 82/53 mm Hg, the pulse 78 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 5 liters per minute. One liter of intravenous fluids was administered, and the blood pressure increased to 108/52 mm Hg. Owing to the patient’s acute illness, the dose of prednisone was increased, and he was admitted to the hospital.
On hospital day 1, fever persisted; the maximum temporal temperature was 39.9°C. The blood pressure remained stable; treatment with intravenous vancomycin was added.
On hospital day 2, pancytopenia developed, and the results of liver-function tests had worsened; laboratory test results are shown in Table 1. Blood and urine cultures showed no growth. A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 67-year-old man with a history of COVID-19 pneumonia and subsequent organizing pneumonia, presenting with fever, myalgias, and vomiting. His symptoms started two days prior to admission, and he also reported a slight increase in shortness of breath. He lives in a rural area and spends time outdoors, which could expose him to various infectious agents. His differential diagnosis includes a bacterial infection, a viral infection, a fungal infection, or a non-infectious cause such as a flare of his underlying interstitial lung disease.\n\nThe patient's blood cultures and urine cultures showed no growth, making a bacterial infection less likely. His respiratory viral panel, including testing for SARS-CoV-2, was negative, making a viral infection less likely. His blood level of 1,3-\u03b2-d-glucan and galactomannan index were within normal limits, making a fungal infection less likely. His CT scan showed resolution of multifocal air-space opacities and new peripheral curvilinear opacity, which could be consistent with a flare of his underlying interstitial lung disease, but this would not typically cause fever and myalgias.\n\nOn hospital day 2, the patient developed pancytopenia and worsening liver function tests. This could be due to a systemic infection, but given the negative cultures and other tests, it could also be due to a non-infectious cause such as an autoimmune or inflammatory condition. However, the patient's history and presentation do not strongly suggest a specific autoimmune or inflammatory condition.\n\nGiven the patient's history of spending time outdoors in a rural area, his symptoms of fever and myalgias, and his development of pancytopenia and worsening liver function tests, a tick-borne illness should be considered. Lyme disease was ruled out with a negative test, but other tick-borne illnesses such as anaplasmosis or ehrlichiosis could present similarly and cause the laboratory abnormalities seen in this patient.\n\nDiagnosis: Anaplasmosis or Ehrlichiosis.""
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}",Anaplasmosis or Ehrlichiosis,Y
 10.1056/NEJMcpc2201249,Case 4-2023: A 56-Year-Old Man with Abnormal Results on Liver Testing,"Alanine aminotransferase (U/liter)	10–50	926	75	92	96	 	72
Aspartate aminotransferase (U/liter)	15–41	1254	116	130	167	 	108
Alkaline phosphatase (U/liter)	32–100	1152	479	585	456	 	427
γ-Glutamyltransferase (U/liter)	8–61	—	—	362	—	8–61	419
Total bilirubin (mg/dl)†	0.0–1.2	8.3	—	2.9	3.4	0.0–1.0	3.3
Direct bilirubin (mg/dl)†	0.0–0.2	—	—	1.3	1.4	0. 	1.6
Hemoglobin (g/dl)	 	—	—	12.4	14.3	 	12.4
Hematocrit (%)	 	—	—	40.2	44.9	 	38.5
White-cell count (per μl)	400 ,000	—	—	4220	2860	 	2230
Platelet count (per μl)	 	—	—	61,000	59,000	 	43,000
Prothrombin time (sec)	12.1–14.7	—	—	14.8	16.6	 	15.5
Prothrombin-time international normalized ratio	 	—	—	1.2	1.4	 	1.2",Primary biliary cholangitis with portopulmonary hypertension.,Primary biliary cholangitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 56-year-old man with a history of alcohol and opioid use was evaluated in the gastroenterology clinic of this hospital because of abnormal results on liver testing.
Table 1.

Laboratory Data.
Three years before the current presentation, the patient had elevated levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase on routine testing performed by his primary care physician. At that time, he reported that testing for hepatitis C virus (HCV) antibodies had been positive in the past. The HCV RNA level was undetectable; other laboratory test results are shown in Table 1. Cessation of alcohol use was advised. Two years before the current presentation, the levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase had decreased; additional laboratory test results obtained at that time are shown in Table 1.
Seven months before the current presentation, the patient was evaluated in the emergency department of another hospital because of pain and swelling in the left wrist that had lasted for 3 weeks. The temporal temperature was 36.6°C. The volar aspect of the left wrist was erythematous and swollen, as was the left knee. Tests for Lyme disease antibodies and rheumatoid factor were negative. Radiographs showed subcutaneous edema of the left knee but no fracture, dislocation, or evidence of advanced arthropathy of the left knee or wrist. A 10-day course of prednisone was prescribed for presumed inflammatory arthritis. The joint swelling and pain resolved.
Six months before the current presentation, the patient was evaluated in the same emergency department because of a painful rash. The temporal temperature was 36.3°C. The distal left forearm was erythematous and had scattered small subcutaneous nodules. Laboratory evaluation revealed pancytopenia, coagulopathy, and elevated levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Blood levels of electrolytes, glucose, and uric acid were normal, as were the results of kidney-function tests; other laboratory test results are shown in Table 1. A plain radiograph of the left wrist showed soft-tissue edema but no abnormalities of the bone. A second course of prednisone was prescribed, and the patient was referred to a dermatologist and a gastroenterologist for consultation.
Two weeks later, the patient was evaluated by a dermatologist affiliated with the other hospital. He had multiple tan macules on the face and trunk, angiomas, and reddish-purple papules (some >1 cm in diameter) on the left forearm. A biopsy of a papule on the left forearm was performed. Histopathological examination of the biopsy specimen revealed nonspecific suppurative and granulomatous dermatitis. No microorganisms were identified, and culture of the biopsy specimen was negative.
Four months before the current presentation, the patient was evaluated by a gastroenterologist affiliated with the other hospital. He had spider angiomas and fullness of the left upper quadrant. On a serum-based test for liver fibrosis (FibroTest), he had a score of 0.96 (with scores of 0.00 to 0.21 indicating no fibrosis and scores of 0.74 to 1.00 indicating severe fibrosis). Imaging studies were obtained.
Figure 1.

MRCP Images.
Dr. William R. Bradley: Magnetic resonance cholangiopancreatography (MRCP) revealed a nodular hepatic contour with patchy perfusion but no focal hepatic lesions (Figure 1A). Splenomegaly, portal vein thrombosis with cavernous transformation, and perigastric, paraesophageal, and splenorenal collateral vessels were also identified (Figure 1B and 1C). There was no dilatation of the intrahepatic bile ducts; the common bile duct measured 8 mm in diameter (Figure 1D).
Dr. Schaefer: Three months before the current evaluation, esophagogastroduodenoscopy and colonoscopy were performed. Grade 2 esophageal varices were identified and banded. Eight days later, the patient was admitted to a second hospital because of new confusion, lethargy, delayed and slurred speech, and visual hallucinations. The blood ammonia level was 99 μmol per liter (169 μg per deciliter; reference range, 11 to 60 μmol per liter [19 to 102 μg per deciliter]). Urinalysis was normal; other laboratory test results are shown in Table 1. A chest radiograph was normal. Abdominal ultrasound images showed persistent splenomegaly and heterogeneous liver echotexture without ascites. A computed tomographic scan of the head, obtained without the administration of intravenous contrast material, was normal. An electrocardiogram showed sinus bradycardia, a pattern consistent with incomplete right bundle-branch block, downsloping ST-segment depressions in the precordium, and a prolonged corrected QT interval. Treatment with lactulose was initiated for a working diagnosis of hepatic encephalopathy. Confusion resolved, and the patient was discharged home on the second hospital day with arrangements made for additional cardiac testing after discharge.
One month before the current evaluation, an echocardiogram showed normal left ventricular size and function, mild right ventricular dilatation, moderate tricuspid regurgitation with right atrial dilatation, and an estimated right ventricular systolic pressure of 71 mm Hg. Perfusion images obtained during vasodilator stress testing showed no evidence of inducible left ventricular ischemia. The patient was referred to the gastroenterology clinic of this hospital for additional evaluation.
In the gastroenterology clinic, the patient reported chronic dyspnea with exertion. He had no orthopnea, chest pain, or palpitations. He had consumed six beers daily for approximately 30 years but had not consumed alcohol during the previous 18 months. Three years before the current presentation, the patient had received a diagnosis of dyslipidemia, with a blood low-density lipoprotein cholesterol level of 337 mg per deciliter (8.7 mmol per liter; reference range, 70 to 129 mg per deciliter [1.8 to 3.3 mmol per liter]) and a total cholesterol level of 380 mg per deciliter (9.8 mmol per liter; reference range, 155 to 199 mg per deciliter [4.0 to 5.1 mmol per liter]). He had a history of opioid use disorder, including intravenous opioids; the disorder had been in remission with the use of buprenorphine–naloxone. Other medical history included depression, insomnia, and multiple knee surgeries. In addition to buprenorphine–naloxone, medications included lactulose, omeprazole, and trazodone. Penicillin had caused a rash. He had worked as a laborer but was disabled and no longer working. He had smoked two cigarettes daily for 30 years. His family history included stroke in his father, diabetes in his mother, and rheumatoid arthritis in his sister.
On examination, the heart rate was 73 beats per minute, the blood pressure 99/65 mm Hg, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 69.9 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.9. He was alert and oriented; asterixis was present. The lung fields were clear, and there was a grade 2/6 holosystolic murmur at the left sternal border. Abdominal examination revealed a palpable hard mass in the epigastrium, a finding that indicated a probable firm caudate lobe of the liver. The knees had healed surgical scars, and there was no edema in the legs. A few spider angiomas were present on the chest. The remainder of the examination was normal. Laboratory test results are shown in Table 1. Serologic testing was negative for antinuclear antibodies and was positive for antimitochondrial antibodies, with a titer of 1:5120.
Additional diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 56-year-old man with a history of alcohol and opioid use was evaluated in the gastroenterology clinic of this hospital because of abnormal results on liver testing.
Table 1.

Laboratory Data.
Three years before the current presentation, the patient had elevated levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase on routine testing performed by his primary care physician. At that time, he reported that testing for hepatitis C virus (HCV) antibodies had been positive in the past. The HCV RNA level was undetectable; other laboratory test results are shown in Table 1. Cessation of alcohol use was advised. Two years before the current presentation, the levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase had decreased; additional laboratory test results obtained at that time are shown in Table 1.
Seven months before the current presentation, the patient was evaluated in the emergency department of another hospital because of pain and swelling in the left wrist that had lasted for 3 weeks. The temporal temperature was 36.6°C. The volar aspect of the left wrist was erythematous and swollen, as was the left knee. Tests for Lyme disease antibodies and rheumatoid factor were negative. Radiographs showed subcutaneous edema of the left knee but no fracture, dislocation, or evidence of advanced arthropathy of the left knee or wrist. A 10-day course of prednisone was prescribed for presumed inflammatory arthritis. The joint swelling and pain resolved.
Six months before the current presentation, the patient was evaluated in the same emergency department because of a painful rash. The temporal temperature was 36.3°C. The distal left forearm was erythematous and had scattered small subcutaneous nodules. Laboratory evaluation revealed pancytopenia, coagulopathy, and elevated levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Blood levels of electrolytes, glucose, and uric acid were normal, as were the results of kidney-function tests; other laboratory test results are shown in Table 1. A plain radiograph of the left wrist showed soft-tissue edema but no abnormalities of the bone. A second course of prednisone was prescribed, and the patient was referred to a dermatologist and a gastroenterologist for consultation.
Two weeks later, the patient was evaluated by a dermatologist affiliated with the other hospital. He had multiple tan macules on the face and trunk, angiomas, and reddish-purple papules (some >1 cm in diameter) on the left forearm. A biopsy of a papule on the left forearm was performed. Histopathological examination of the biopsy specimen revealed nonspecific suppurative and granulomatous dermatitis. No microorganisms were identified, and culture of the biopsy specimen was negative.
Four months before the current presentation, the patient was evaluated by a gastroenterologist affiliated with the other hospital. He had spider angiomas and fullness of the left upper quadrant. On a serum-based test for liver fibrosis (FibroTest), he had a score of 0.96 (with scores of 0.00 to 0.21 indicating no fibrosis and scores of 0.74 to 1.00 indicating severe fibrosis). Imaging studies were obtained.
Figure 1.

MRCP Images.
Dr. William R. Bradley: Magnetic resonance cholangiopancreatography (MRCP) revealed a nodular hepatic contour with patchy perfusion but no focal hepatic lesions (Figure 1A). Splenomegaly, portal vein thrombosis with cavernous transformation, and perigastric, paraesophageal, and splenorenal collateral vessels were also identified (Figure 1B and 1C). There was no dilatation of the intrahepatic bile ducts; the common bile duct measured 8 mm in diameter (Figure 1D).
Dr. Schaefer: Three months before the current evaluation, esophagogastroduodenoscopy and colonoscopy were performed. Grade 2 esophageal varices were identified and banded. Eight days later, the patient was admitted to a second hospital because of new confusion, lethargy, delayed and slurred speech, and visual hallucinations. The blood ammonia level was 99 μmol per liter (169 μg per deciliter; reference range, 11 to 60 μmol per liter [19 to 102 μg per deciliter]). Urinalysis was normal; other laboratory test results are shown in Table 1. A chest radiograph was normal. Abdominal ultrasound images showed persistent splenomegaly and heterogeneous liver echotexture without ascites. A computed tomographic scan of the head, obtained without the administration of intravenous contrast material, was normal. An electrocardiogram showed sinus bradycardia, a pattern consistent with incomplete right bundle-branch block, downsloping ST-segment depressions in the precordium, and a prolonged corrected QT interval. Treatment with lactulose was initiated for a working diagnosis of hepatic encephalopathy. Confusion resolved, and the patient was discharged home on the second hospital day with arrangements made for additional cardiac testing after discharge.
One month before the current evaluation, an echocardiogram showed normal left ventricular size and function, mild right ventricular dilatation, moderate tricuspid regurgitation with right atrial dilatation, and an estimated right ventricular systolic pressure of 71 mm Hg. Perfusion images obtained during vasodilator stress testing showed no evidence of inducible left ventricular ischemia. The patient was referred to the gastroenterology clinic of this hospital for additional evaluation.
In the gastroenterology clinic, the patient reported chronic dyspnea with exertion. He had no orthopnea, chest pain, or palpitations. He had consumed six beers daily for approximately 30 years but had not consumed alcohol during the previous 18 months. Three years before the current presentation, the patient had received a diagnosis of dyslipidemia, with a blood low-density lipoprotein cholesterol level of 337 mg per deciliter (8.7 mmol per liter; reference range, 70 to 129 mg per deciliter [1.8 to 3.3 mmol per liter]) and a total cholesterol level of 380 mg per deciliter (9.8 mmol per liter; reference range, 155 to 199 mg per deciliter [4.0 to 5.1 mmol per liter]). He had a history of opioid use disorder, including intravenous opioids; the disorder had been in remission with the use of buprenorphine–naloxone. Other medical history included depression, insomnia, and multiple knee surgeries. In addition to buprenorphine–naloxone, medications included lactulose, omeprazole, and trazodone. Penicillin had caused a rash. He had worked as a laborer but was disabled and no longer working. He had smoked two cigarettes daily for 30 years. His family history included stroke in his father, diabetes in his mother, and rheumatoid arthritis in his sister.
On examination, the heart rate was 73 beats per minute, the blood pressure 99/65 mm Hg, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 69.9 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.9. He was alert and oriented; asterixis was present. The lung fields were clear, and there was a grade 2/6 holosystolic murmur at the left sternal border. Abdominal examination revealed a palpable hard mass in the epigastrium, a finding that indicated a probable firm caudate lobe of the liver. The knees had healed surgical scars, and there was no edema in the legs. A few spider angiomas were present on the chest. The remainder of the examination was normal. Laboratory test results are shown in Table 1. Serologic testing was negative for antinuclear antibodies and was positive for antimitochondrial antibodies, with a titer of 1:5120.
Additional diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of alcohol and opioid use, which can both cause liver damage. He has elevated levels of liver enzymes, indicating liver damage. He also has a history of hepatitis C, which can cause liver damage and cirrhosis. The patient has symptoms of liver disease, including spider angiomas and a hard mass in the epigastrium, which is likely a firm caudate lobe of the liver. He also has symptoms of hepatic encephalopathy, including confusion, lethargy, and visual hallucinations, which is a complication of liver disease. The patient's MRCP images show a nodular hepatic contour with patchy perfusion, splenomegaly, portal vein thrombosis with cavernous transformation, and perigastric, paraesophageal, and splenorenal collateral vessels, all of which are indicative of cirrhosis. The patient's FibroTest score indicates severe fibrosis. The patient's serologic testing was positive for antimitochondrial antibodies, which is indicative of primary biliary cirrhosis. \n\nDiagnosis: Primary Biliary Cirrhosis.""
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}",Primary Biliary Cirrhosis,Y,"{
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        ""content"": ""The patient is a 56-year-old man with a history of alcohol and opioid use who presents with abnormal liver function tests, including elevated levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. He also has a history of hepatitis C, although his HCV RNA level is currently undetectable. His symptoms and history suggest a liver disease, and the differential diagnosis includes alcoholic liver disease, hepatitis C, autoimmune hepatitis, and primary biliary cirrhosis. Alcoholic liver disease is a possibility given his history of alcohol use, but his liver function tests improved after he stopped drinking, suggesting another cause. Hepatitis C is also a possibility given his history, but his HCV RNA level is undetectable, making this less likely. Autoimmune hepatitis is a possibility given his elevated liver function tests and the presence of antinuclear antibodies, but this is less likely given his negative antinuclear antibody test. Primary biliary cirrhosis is a possibility given his elevated liver function tests and the presence of antimitochondrial antibodies, which are typically present in this condition. His imaging studies also show signs of liver disease, including a nodular hepatic contour and splenomegaly. Given these findings, primary biliary cirrhosis is the most likely diagnosis.\n\nDiagnosis: Primary Biliary Cirrhosis.""
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10.1056/NEJMcpc2211367,Case 3-2023: A 16-Year-Old Girl with Abdominal Pain and Bloody Diarrhea,"Hemoglobin (g/dl)	 	9.8	8.8
Hematocrit (%)	 	31.4	27.6
Platelet count (per μl)	 	188,000	67,000
White-cell count (per μl)	450 ,000	10,690	13,490
Differential count (per μl)			
Neutrophils	180 100	9000	10,020
Lymphocytes	1200–5200	1120	2290
Monocytes	20 00	360	780
Eosinophils	0–1000	100	140
Basophils	 0	30	20
Prothrombin time (sec)	 	16.6	17.3
Prothrombin-time international normalized ratio	 	1.4	1.4
Activated partial-thromboplastin time (sec)	22. 6.0	47.0	50.0
d-dimer (ng/ml)	 	—	>10,000
Erythrocyte sedimentation rate (mm/hr)	 0	71	—
C-reactive protein (mg/liter)	0. .0	248.0	66.9
Lactate dehydrogenase (U/liter)	11 10	—	299",Catastrophic antiphospholipid syndrome.,Catastrophic antiphospholipid syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 16-year-old girl was admitted to this hospital because of abdominal pain and bloody diarrhea.
The patient had been well until 5 weeks before this admission, when diarrhea and intermittent, diffuse, crampy abdominal pain developed. During the subsequent week, the diarrhea occurred more frequently, and the abdominal pain worsened in severity, such that it sometimes awoke the patient from sleep. Four weeks before this admission, the diarrhea began to contain dark-red blood. The patient’s mother took her to the primary care clinic of another hospital.
In the primary care clinic, the weight was 98.7 kg; the physical examination was otherwise normal. The hemoglobin level was 12.5 g per deciliter (reference range, 12.0 to 16.0). Stool cultures for salmonella, shigella, campylobacter, and Escherichia coli O157:H7 were negative, as were antigen tests for giardia, cryptosporidium, and Clostridioides difficile toxin. Empirical treatment with ciprofloxacin was started.
During the next 3 weeks, the patient completed the course of ciprofloxacin as instructed, but the abdominal pain and bloody diarrhea continued. On the day of this admission, diarrhea occurred at least four times. The patient’s parents called the primary care clinic and were instructed to bring her to the emergency department of this hospital.
On evaluation, the patient reported fatigue, malaise, weight loss, decreased appetite, and intermittent nausea and vomiting when she ate food. She also had headache and mild, diffuse joint and muscle pain. She had had no fever or sick contacts.
The patient had obesity, anxiety, and attention deficit–hyperactivity disorder (ADHD). Medications included fluoxetine and dextroamphetamine–amphetamine; there were no known drug allergies. Menarche had occurred when she was 11 years of age, and her last menstrual period had been 2 months earlier. She did not drink alcohol or use illicit drugs, and she did not vape or smoke tobacco. The patient lived in a rural area of New England with her mother, father, and sister, as well as her pet dog, cat, and lizard. She attended a technical high school with an emphasis on agriculture, and she had frequent interactions with marine and farm animals through school. Her family history included colorectal cancer and amyotrophic lateral sclerosis in her maternal grandfather, diverticulosis in her maternal grandmother and mother, psoriasis in her maternal grandmother and uncle, and celiac disease in her paternal cousin. Her father had hyperlipidemia, and her mother had had one miscarriage, which had occurred in the first trimester of pregnancy.
On examination, the temporal temperature was 36.4°C, the heart rate 112 beats per minute, and the blood pressure 94/68 mm Hg. The weight was 89.8 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.7. The patient appeared pale, tired, and uncomfortable because of pain. The mucous membranes were dry. The abdomen was nondistended, and there was mild tenderness in both lower quadrants. There was no ulceration or rash.
Table 1.

Laboratory Data.
The white-cell count was 10,690 per microliter (reference range in children 12 to 17 years of age, 4500 to 10,700), the platelet count 188,000 per microliter, and the hemoglobin level 9.8 g per deciliter. The blood level of C-reactive protein was 248.0 mg per liter (reference range, 0.0 to 8.0), and the erythrocyte sedimentation rate was 71 mm per hour (reference range, 0 to 20). The blood levels of electrolytes and glucose were normal, as were the results of kidney-function tests. Other laboratory test results are shown in Table 1. Testing for severe acute respiratory syndrome coronavirus 2 was negative. Intravenous fluids, acetaminophen, and ondansetron were administered, and the patient was admitted to this hospital.
On hospital day 2, the hemoglobin level was 8.2 g per deciliter, and one unit of packed red cells was transfused. Esophagogastroduodenoscopy (EGD) and colonoscopy were performed.
Figure 1.

Images Obtained during Esophagogastroduodenoscopy and Colonoscopy.
Dr. Maureen M. Leonard: On EGD, two cratered esophageal ulcers were located 30 cm from the incisors (Figure 1A). The proximal, middle, and distal portions of the esophagus were normal. Diffuse mild inflammation — characterized by erythema and friability — was found in the cardia, gastric fundus, and gastric antrum (Figure 1B). The duodenum appeared normal. Biopsy specimens were obtained throughout the procedure for histologic evaluation.
When the patient was being positioned on the procedure table for the colonoscopy, a large volume of bright-red blood was noted to be draining from the rectum. Perianal and digital rectal examinations did not reveal a source of bleeding. Emergency radiography of the abdomen did not reveal free air, and the colonoscopy was started. On colonoscopy, the rectum and proximal sigmoid colon appeared normal (Figure 1C). However, as the colonoscope was advanced farther into the sigmoid colon, multiple nonobstructing, large, friable, dark-violet lesions were identified and biopsied (Figure 1D, 1E, and 1F). Because of narrowing and severe friability, the area was not traversed with the endoscope, and the procedure was aborted.
Dr. Mauney: The patient was transferred to the pediatric intensive care unit of this hospital. During the subsequent 2 days, an additional two units of packed red cells were transfused. Treatment with pantoprazole was started.
Figure 2.

Initial Imaging Studies.
Dr. Sjirk J. Westra: Computed tomography (CT) of the abdomen and chest was performed (Figure 2A through 2D). There was irregular thickening of the large bowel wall and adjacent fat stranding, with sparing of the distal sigmoid colon and rectum. The kidneys had multifocal patchy areas of hypoattenuation.
Dr. Mauney: On hospital day 5, tachycardia and tachypnea developed. The hemoglobin level was 8.8 g per deciliter, and the platelet count was 67,000 per microliter. The prothrombin time was 17.3 seconds (reference range, 11.5 to 14.5), the prothrombin-time international normalized ratio 1.4 (reference range, 0.9 to 1.1), the activated partial-thromboplastin time 50.0 seconds (reference range, 22.0 to 36.0), and the blood d-dimer level greater than 10,000 ng per milliliter (reference range, 0 to 500). Other laboratory test results are shown in Table 1.
Dr. Westra: Thoracic CT angiography revealed a central filling defect in the distal right pulmonary artery, a finding consistent with pulmonary embolism (Figure 2E). There was also a large right pleural effusion.
Dr. Mauney: A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 16-year-old girl was admitted to this hospital because of abdominal pain and bloody diarrhea.
The patient had been well until 5 weeks before this admission, when diarrhea and intermittent, diffuse, crampy abdominal pain developed. During the subsequent week, the diarrhea occurred more frequently, and the abdominal pain worsened in severity, such that it sometimes awoke the patient from sleep. Four weeks before this admission, the diarrhea began to contain dark-red blood. The patient’s mother took her to the primary care clinic of another hospital.
In the primary care clinic, the weight was 98.7 kg; the physical examination was otherwise normal. The hemoglobin level was 12.5 g per deciliter (reference range, 12.0 to 16.0). Stool cultures for salmonella, shigella, campylobacter, and Escherichia coli O157:H7 were negative, as were antigen tests for giardia, cryptosporidium, and Clostridioides difficile toxin. Empirical treatment with ciprofloxacin was started.
During the next 3 weeks, the patient completed the course of ciprofloxacin as instructed, but the abdominal pain and bloody diarrhea continued. On the day of this admission, diarrhea occurred at least four times. The patient’s parents called the primary care clinic and were instructed to bring her to the emergency department of this hospital.
On evaluation, the patient reported fatigue, malaise, weight loss, decreased appetite, and intermittent nausea and vomiting when she ate food. She also had headache and mild, diffuse joint and muscle pain. She had had no fever or sick contacts.
The patient had obesity, anxiety, and attention deficit–hyperactivity disorder (ADHD). Medications included fluoxetine and dextroamphetamine–amphetamine; there were no known drug allergies. Menarche had occurred when she was 11 years of age, and her last menstrual period had been 2 months earlier. She did not drink alcohol or use illicit drugs, and she did not vape or smoke tobacco. The patient lived in a rural area of New England with her mother, father, and sister, as well as her pet dog, cat, and lizard. She attended a technical high school with an emphasis on agriculture, and she had frequent interactions with marine and farm animals through school. Her family history included colorectal cancer and amyotrophic lateral sclerosis in her maternal grandfather, diverticulosis in her maternal grandmother and mother, psoriasis in her maternal grandmother and uncle, and celiac disease in her paternal cousin. Her father had hyperlipidemia, and her mother had had one miscarriage, which had occurred in the first trimester of pregnancy.
On examination, the temporal temperature was 36.4°C, the heart rate 112 beats per minute, and the blood pressure 94/68 mm Hg. The weight was 89.8 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.7. The patient appeared pale, tired, and uncomfortable because of pain. The mucous membranes were dry. The abdomen was nondistended, and there was mild tenderness in both lower quadrants. There was no ulceration or rash.
Table 1.

Laboratory Data.
The white-cell count was 10,690 per microliter (reference range in children 12 to 17 years of age, 4500 to 10,700), the platelet count 188,000 per microliter, and the hemoglobin level 9.8 g per deciliter. The blood level of C-reactive protein was 248.0 mg per liter (reference range, 0.0 to 8.0), and the erythrocyte sedimentation rate was 71 mm per hour (reference range, 0 to 20). The blood levels of electrolytes and glucose were normal, as were the results of kidney-function tests. Other laboratory test results are shown in Table 1. Testing for severe acute respiratory syndrome coronavirus 2 was negative. Intravenous fluids, acetaminophen, and ondansetron were administered, and the patient was admitted to this hospital.
On hospital day 2, the hemoglobin level was 8.2 g per deciliter, and one unit of packed red cells was transfused. Esophagogastroduodenoscopy (EGD) and colonoscopy were performed.
Figure 1.

Images Obtained during Esophagogastroduodenoscopy and Colonoscopy.
Dr. Maureen M. Leonard: On EGD, two cratered esophageal ulcers were located 30 cm from the incisors (Figure 1A). The proximal, middle, and distal portions of the esophagus were normal. Diffuse mild inflammation — characterized by erythema and friability — was found in the cardia, gastric fundus, and gastric antrum (Figure 1B). The duodenum appeared normal. Biopsy specimens were obtained throughout the procedure for histologic evaluation.
When the patient was being positioned on the procedure table for the colonoscopy, a large volume of bright-red blood was noted to be draining from the rectum. Perianal and digital rectal examinations did not reveal a source of bleeding. Emergency radiography of the abdomen did not reveal free air, and the colonoscopy was started. On colonoscopy, the rectum and proximal sigmoid colon appeared normal (Figure 1C). However, as the colonoscope was advanced farther into the sigmoid colon, multiple nonobstructing, large, friable, dark-violet lesions were identified and biopsied (Figure 1D, 1E, and 1F). Because of narrowing and severe friability, the area was not traversed with the endoscope, and the procedure was aborted.
Dr. Mauney: The patient was transferred to the pediatric intensive care unit of this hospital. During the subsequent 2 days, an additional two units of packed red cells were transfused. Treatment with pantoprazole was started.
Figure 2.

Initial Imaging Studies.
Dr. Sjirk J. Westra: Computed tomography (CT) of the abdomen and chest was performed (Figure 2A through 2D). There was irregular thickening of the large bowel wall and adjacent fat stranding, with sparing of the distal sigmoid colon and rectum. The kidneys had multifocal patchy areas of hypoattenuation.
Dr. Mauney: On hospital day 5, tachycardia and tachypnea developed. The hemoglobin level was 8.8 g per deciliter, and the platelet count was 67,000 per microliter. The prothrombin time was 17.3 seconds (reference range, 11.5 to 14.5), the prothrombin-time international normalized ratio 1.4 (reference range, 0.9 to 1.1), the activated partial-thromboplastin time 50.0 seconds (reference range, 22.0 to 36.0), and the blood d-dimer level greater than 10,000 ng per milliliter (reference range, 0 to 500). Other laboratory test results are shown in Table 1.
Dr. Westra: Thoracic CT angiography revealed a central filling defect in the distal right pulmonary artery, a finding consistent with pulmonary embolism (Figure 2E). There was also a large right pleural effusion.
Dr. Mauney: A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of abdominal pain, bloody diarrhea, weight loss, and decreased appetite, along with the findings of esophageal ulcers and inflammation in the cardia, gastric fundus, and gastric antrum, suggest a gastrointestinal disorder. The negative stool cultures and lack of response to antibiotics rule out a bacterial infection. The presence of large, friable, dark-violet lesions in the sigmoid colon further supports a non-infectious cause. The patient's history of interactions with marine and farm animals through school, along with the CT findings of irregular thickening of the large bowel wall and multifocal patchy areas of hypoattenuation in the kidneys, suggest a parasitic infection. The development of tachycardia, tachypnea, and a pulmonary embolism indicate a systemic response to the infection. \n\nDiagnosis: \nParasitic infection, likely Schistosomiasis.""
      },
      ""finish_reason"": ""stop""
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  ""usage"": {
    ""prompt_tokens"": 3399,
    ""completion_tokens"": 186,
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}","{
  ""id"": ""chatcmpl-7hskjuGHMeqDzZdFh5j6WTLnwX1xY"",
  ""object"": ""chat.completion"",
  ""created"": 1690692929,
  ""model"": ""gpt-4-0613"",
  ""choices"": [
    {
      ""index"": 0,
      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient presents with abdominal pain and bloody diarrhea, which are symptoms of gastrointestinal disease. The patient's history of exposure to farm animals and her symptoms suggest a possible zoonotic infection. However, stool cultures for common bacterial pathogens were negative, and her symptoms did not improve with antibiotic treatment, suggesting a non-infectious cause. The patient's symptoms, along with her laboratory findings of anemia and elevated inflammatory markers, are consistent with inflammatory bowel disease (IBD). However, the presence of esophageal ulcers and gastric inflammation seen on endoscopy are not typical for IBD. The presence of large, friable, dark-violet lesions in the sigmoid colon seen on colonoscopy, along with the CT findings of irregular thickening of the large bowel wall and multifocal patchy areas of hypoattenuation in the kidneys, are suggestive of vascular disease. The development of pulmonary embolism further supports a vascular cause. Taken together, these findings suggest a diagnosis of vasculitis affecting the gastrointestinal tract and other organs.\n\nDiagnosis: Vasculitis.""
      },
      ""finish_reason"": ""stop""
    }
  ],
  ""usage"": {
    ""prompt_tokens"": 3413,
    ""completion_tokens"": 216,
    ""total_tokens"": 3629
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}",Vasculitis,N,"{
  ""id"": ""chatcmpl-7hslMD5KmkUiFHD4V9qZHE0zqSrqT"",
  ""object"": ""chat.completion"",
  ""created"": 1690692968,
  ""model"": ""gpt-4-0613"",
  ""choices"": [
    {
      ""index"": 0,
      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient is a 16-year-old girl presenting with abdominal pain, bloody diarrhea, weight loss, and decreased appetite. The differential diagnosis for this patient includes inflammatory bowel disease (Crohn's disease or ulcerative colitis), infectious colitis, ischemic colitis, and colorectal cancer. The patient's stool cultures for common bacterial pathogens were negative, making infectious colitis less likely. The patient's young age and lack of risk factors make ischemic colitis and colorectal cancer less likely. The patient's symptoms, including bloody diarrhea, weight loss, and abdominal pain, are consistent with inflammatory bowel disease. The patient's endoscopy and colonoscopy findings, including esophageal ulcers and inflammation in the cardia, gastric fundus, and gastric antrum, as well as large, friable, dark-violet lesions in the sigmoid colon, are also consistent with inflammatory bowel disease. The patient's laboratory findings, including an elevated white blood cell count, C-reactive protein, and erythrocyte sedimentation rate, suggest an inflammatory process. The patient's CT findings, including irregular thickening of the large bowel wall and adjacent fat stranding, are also consistent with inflammatory bowel disease. \n\nDiagnosis: Inflammatory bowel disease (specific subtype to be determined by biopsy results).""
      },
      ""finish_reason"": ""stop""
    }
  ],
  ""usage"": {
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}",Inflammatory bowel disease (specific subtype to be determined by biopsy results),N
10.1056/NEJMcpc2201240,Case 2-2023: A 76-Year-Old Man with Dizziness and Altered Mental Status,"Sodium (mmol/liter)	 	140	145	143
Potassium (mmol/liter)	 	4.3	3.0	3.6
Chloride (mmol/liter)	 	106	111	111
Carbon dioxide (mmol/liter)	 	15	15	16
Urea nitrogen (mg/dl)	 	19	18	20
Creatinine (mg/dl)	 	1.57	1.32	1.42
Glucose (mg/dl)	 	142	74	74
Calcium (mg/dl)	 	7.8	7.3	7.7
Albumin (g/dl)	 	3.8	3.8	3.5
Lactate (mmol/liter)	 	2.1	1.1	—
High-sensitivity troponin T (ng/liter)	0–9	41	44	—
Hemoglobin (g/dl)	 	13.2	12.6	11.7
Hematocrit (%)	 	39.7	38.1	36.0
Prothrombin time (sec)	 	30.2	35.9	—
Prothrombin-time international normalized ratio	 	2.9	3.6	—
d-dimer (ng/ml)	 	2075	—	—
Thyrotropin (μIU/ml)	0.4 0	—	0.25	—
Free thyroxine (ng/dl)	0.9–1.8	—	0.8	—
Triiodothyronine (ng/dl)	60–181	—	31	—
Iron (μg/dl)	30–160	—	40	—
Iron-binding capacity (μg/dl)	23 4	—	320	—
Ferritin (μg/liter)	1 00	—	39	—
Vitamin B12 (pg/ml)	>231	—	383	—
25-Hydroxyvitamin D (ng/ml)	2 0	—	9	—
Arterial blood gas				
Fraction of inspired oxygen	—	—	—	0.21
pH	 	—	—	7.50
Partial pressure of carbon dioxide (mm Hg)	 	—	—	21
Partial pressure of oxygen (mm Hg)	 	—	—	68
Bicarbonate (mmol/liter)	24–30	—	—	16
Urine				
Color	Yellow	Yellow	—	—
Clarity	Clear	Clear	—	—
pH	 	6.0	—	—
Specific gravity	 	1.034	—	—
Glucose	Negative	Negative	—	—
Ketones	Negative	2+	—	—
Leukocyte esterase	Negative	Negative	—	—
Nitrite	Negative	Negative	—	—
Blood	Negative	1+	—	—
Protein	Negative	Negative	—	—
Erythrocytes (per high-power field)	 	1 0	—	—
Leukocytes (per high-power field)	 	 	—	—
Bacteria	None	None	—	—",Chronic salicylate toxicity.,Salicylate toxicity,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old man was evaluated in the emergency department of this hospital because of dizziness and altered mental status.
On the day of the current evaluation, the patient was observed crawling on a city sidewalk. He appeared pale and diaphoretic. On evaluation by emergency medical services, he reported feeling dizzy and “weird.” A fingerstick blood glucose level was 152 mg per deciliter (8.4 mmol per liter). He was brought to the emergency department of this hospital for further evaluation.
In the emergency department, the patient could not recall recent events, but he reported shortness of breath, as well as chronic back pain and persistent ringing in the ears. He was unable to give additional details of his history, but he provided the name of the hospital where he routinely received care. On a phone consultation, physicians at that hospital reported that the patient had a history of traumatic brain injury, post-traumatic stress disorder, seizure disorder, chronic back pain due to spinal stenosis, hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, gastroesophageal reflux disease, and anxiety. Prescribed medications included lisinopril and transdermal lidocaine. There were no known drug allergies. The patient had consumed alcohol in the past but not for 40 years. His family history was unknown.
The temporal temperature was 36.6°C, the heart rate 92 beats per minute, the blood pressure 183/113 mm Hg, the respiratory rate 27 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The patient appeared disheveled and diaphoretic. He was somnolent but awakened to verbal stimuli. He was oriented to person, place, and time but only intermittently followed commands. A small superficial skin abrasion was noted above the left eyebrow. There was mild tenderness on palpation of the midback but no other evidence of trauma. The remainder of the examination was normal.
Table 1.

Laboratory Data.
Point-of-care ultrasonography, performed with an approach known as FAST (focused assessment with sonography for trauma), showed no abnormalities. The blood ethanol level was undetectable, and urine toxicologic testing was negative for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates. The blood levels of lipase, magnesium, and N-terminal pro–B-type natriuretic peptide were normal, as were results of liver-function tests. There was mild normocytic anemia, but the complete blood count with differential count was otherwise normal. Other laboratory test results are shown in Table 1. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 was negative. Samples of blood and urine were obtained for culture. An electrocardiogram showed sinus rhythm, intraventricular conduction delay, left axis deviation, and nonspecific minor ST-segment and T-wave abnormalities. Imaging studies were obtained.
Figure 1.

Initial Imaging Studies.
Dr. Brooks P. Applewhite: Radiographs of the chest and pelvis showed no acute abnormalities. Computed tomographic (CT) angiography of the head and neck (Figure 1A) revealed nonspecific mild white-matter changes, a nonspecific small focal calcification in the right-peritrigonal white matter, atherosclerosis without high-grade cerebrovascular stenosis, and multilevel spondylotic changes without severe spinal canal stenosis. There was no evidence of acute intracranial hemorrhage or territorial infarction. CT angiography of the chest, abdomen, and pelvis (Figure 1B and 1C) revealed no evidence of aortic dissection, pulmonary embolism, pneumothorax, pulmonary edema, lung consolidation, or pericardial effusion. There was a left adrenal nodule that measured 19 mm in diameter, a finding consistent with an adenoma.
Dr. Karandinos: Normal saline with 5% dextrose was administered intravenously. During the next 8 hours, the patient was agitated and combative. He repeatedly removed peripheral intravenous catheters and disconnected monitors. He was no longer oriented to place or time. Two doses of olanzapine were administered intravenously, and the patient slept for several hours during the night.
Sixteen hours after the patient arrived in the emergency department, the temporal temperature was 37.7°C, the heart rate 78 beats per minute, the blood pressure 160/72 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The patient was observed to be breathing deeply. He was able to state his name, but his speech was otherwise nonsensical and dysarthric. He followed commands only when visual cues were given; for example, he stuck out his tongue after the examiner demonstrated the task. Motor, sensory, and reflex examinations were normal; tests of cerebellar function were not performed. Additional laboratory test results are shown in Table 1. The results of electroencephalography (EEG) were normal, without epileptiform abnormalities. Normal saline with potassium chloride was administered intravenously, as was lorazepam. Additional imaging studies were obtained.
Figure 2.

MRI of the Head.
Dr. Applewhite: Magnetic resonance imaging (MRI) of the head (Figure 2) revealed no evidence of acute intracranial hemorrhage or acute or subacute infarction. T2-weighted fluid-attenuated inversion recovery images showed a mild burden of white-matter signal hyperintensities, which are nonspecific but typical of chronic small-vessel disease. The previously detected calcification in the right-peritrigonal white matter correlated with an 8-mm focus of T1 and T2 signal abnormalities with associated susceptibility blooming, a finding suggestive of either a calcified cavernous malformation or sequelae of previous infection or inflammation.
Dr. Karandinos: The patient’s mental status did not improve. Twenty-four hours after he arrived in the emergency department, he was admitted to the hospital with a working diagnosis of seizure. The temporal temperature was 37.6°C, the heart rate 77 beats per minute, the blood pressure 151/70 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. Respiratory effort appeared increased. He was somnolent, and he followed simple commands but did not open his eyes in response to sternal rub. The blood levels of creatine kinase, fibrinogen, and ammonia were normal. Other laboratory test results are shown in Table 1.
Thiamine was administered intravenously. Additional diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old man was evaluated in the emergency department of this hospital because of dizziness and altered mental status.
On the day of the current evaluation, the patient was observed crawling on a city sidewalk. He appeared pale and diaphoretic. On evaluation by emergency medical services, he reported feeling dizzy and “weird.” A fingerstick blood glucose level was 152 mg per deciliter (8.4 mmol per liter). He was brought to the emergency department of this hospital for further evaluation.
In the emergency department, the patient could not recall recent events, but he reported shortness of breath, as well as chronic back pain and persistent ringing in the ears. He was unable to give additional details of his history, but he provided the name of the hospital where he routinely received care. On a phone consultation, physicians at that hospital reported that the patient had a history of traumatic brain injury, post-traumatic stress disorder, seizure disorder, chronic back pain due to spinal stenosis, hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, gastroesophageal reflux disease, and anxiety. Prescribed medications included lisinopril and transdermal lidocaine. There were no known drug allergies. The patient had consumed alcohol in the past but not for 40 years. His family history was unknown.
The temporal temperature was 36.6°C, the heart rate 92 beats per minute, the blood pressure 183/113 mm Hg, the respiratory rate 27 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The patient appeared disheveled and diaphoretic. He was somnolent but awakened to verbal stimuli. He was oriented to person, place, and time but only intermittently followed commands. A small superficial skin abrasion was noted above the left eyebrow. There was mild tenderness on palpation of the midback but no other evidence of trauma. The remainder of the examination was normal.
Table 1.

Laboratory Data.
Point-of-care ultrasonography, performed with an approach known as FAST (focused assessment with sonography for trauma), showed no abnormalities. The blood ethanol level was undetectable, and urine toxicologic testing was negative for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates. The blood levels of lipase, magnesium, and N-terminal pro–B-type natriuretic peptide were normal, as were results of liver-function tests. There was mild normocytic anemia, but the complete blood count with differential count was otherwise normal. Other laboratory test results are shown in Table 1. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 was negative. Samples of blood and urine were obtained for culture. An electrocardiogram showed sinus rhythm, intraventricular conduction delay, left axis deviation, and nonspecific minor ST-segment and T-wave abnormalities. Imaging studies were obtained.
Figure 1.

Initial Imaging Studies.
Dr. Brooks P. Applewhite: Radiographs of the chest and pelvis showed no acute abnormalities. Computed tomographic (CT) angiography of the head and neck (Figure 1A) revealed nonspecific mild white-matter changes, a nonspecific small focal calcification in the right-peritrigonal white matter, atherosclerosis without high-grade cerebrovascular stenosis, and multilevel spondylotic changes without severe spinal canal stenosis. There was no evidence of acute intracranial hemorrhage or territorial infarction. CT angiography of the chest, abdomen, and pelvis (Figure 1B and 1C) revealed no evidence of aortic dissection, pulmonary embolism, pneumothorax, pulmonary edema, lung consolidation, or pericardial effusion. There was a left adrenal nodule that measured 19 mm in diameter, a finding consistent with an adenoma.
Dr. Karandinos: Normal saline with 5% dextrose was administered intravenously. During the next 8 hours, the patient was agitated and combative. He repeatedly removed peripheral intravenous catheters and disconnected monitors. He was no longer oriented to place or time. Two doses of olanzapine were administered intravenously, and the patient slept for several hours during the night.
Sixteen hours after the patient arrived in the emergency department, the temporal temperature was 37.7°C, the heart rate 78 beats per minute, the blood pressure 160/72 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The patient was observed to be breathing deeply. He was able to state his name, but his speech was otherwise nonsensical and dysarthric. He followed commands only when visual cues were given; for example, he stuck out his tongue after the examiner demonstrated the task. Motor, sensory, and reflex examinations were normal; tests of cerebellar function were not performed. Additional laboratory test results are shown in Table 1. The results of electroencephalography (EEG) were normal, without epileptiform abnormalities. Normal saline with potassium chloride was administered intravenously, as was lorazepam. Additional imaging studies were obtained.
Figure 2.

MRI of the Head.
Dr. Applewhite: Magnetic resonance imaging (MRI) of the head (Figure 2) revealed no evidence of acute intracranial hemorrhage or acute or subacute infarction. T2-weighted fluid-attenuated inversion recovery images showed a mild burden of white-matter signal hyperintensities, which are nonspecific but typical of chronic small-vessel disease. The previously detected calcification in the right-peritrigonal white matter correlated with an 8-mm focus of T1 and T2 signal abnormalities with associated susceptibility blooming, a finding suggestive of either a calcified cavernous malformation or sequelae of previous infection or inflammation.
Dr. Karandinos: The patient’s mental status did not improve. Twenty-four hours after he arrived in the emergency department, he was admitted to the hospital with a working diagnosis of seizure. The temporal temperature was 37.6°C, the heart rate 77 beats per minute, the blood pressure 151/70 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. Respiratory effort appeared increased. He was somnolent, and he followed simple commands but did not open his eyes in response to sternal rub. The blood levels of creatine kinase, fibrinogen, and ammonia were normal. Other laboratory test results are shown in Table 1.
Thiamine was administered intravenously. Additional diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Wernicke's Encephalopathy. The patient's history of alcoholism, combined with his symptoms of altered mental status, dizziness, and inability to recall recent events, are indicative of Wernicke's Encephalopathy. This condition is caused by a deficiency in thiamine, which is common in individuals with a history of alcoholism. The administration of thiamine further supports this diagnosis.""
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        ""content"": ""The patient's symptoms of dizziness, altered mental status, and deep breathing, along with the laboratory findings of elevated anion gap metabolic acidosis and elevated lactate levels, suggest a diagnosis of lactic acidosis. The patient's history of diabetes mellitus and chronic kidney disease could contribute to this condition. The lack of improvement in the patient's mental status despite treatment and the absence of other causes of altered mental status (such as infection, trauma, or drug intoxication) further support this diagnosis.\n\nDiagnosis: Lactic Acidosis.""
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        ""content"": ""The patient is a 76-year-old man presenting with dizziness, altered mental status, and shortness of breath. His medical history includes traumatic brain injury, post-traumatic stress disorder, seizure disorder, chronic back pain due to spinal stenosis, hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, gastroesophageal reflux disease, and anxiety. The differential diagnosis for this patient includes stroke, seizure, metabolic encephalopathy, infection, and drug intoxication. \n\nStroke is less likely given the absence of focal neurological deficits and normal imaging studies. Seizure is a possibility given the patient's history, but the normal EEG makes this less likely. Metabolic encephalopathy could be caused by a number of conditions including renal or liver failure, but the patient's lab results do not support this. Infection could cause altered mental status, but the patient does not have a fever or other signs of infection. Drug intoxication is also a possibility, but the patient's toxicology screen was negative.\n\nThe patient's lab results show a high anion gap metabolic acidosis with an elevated lactate level. This could be due to a number of conditions including sepsis, shock, or certain types of poisoning. However, the patient does not have signs of infection or shock, and his toxicology screen was negative. The patient's history of diabetes suggests the possibility of diabetic ketoacidosis, but his blood glucose level is not particularly high and he does not have ketonuria.\n\nThe patient's lab results also show a high osmolal gap. This could be due to a number of conditions including alcohol intoxication, ethylene glycol poisoning, or methanol poisoning. However, the patient's alcohol level was undetectable and his toxicology screen was negative.\n\nGiven the patient's high anion gap metabolic acidosis, elevated lactate level, and high osmolal gap, the most likely diagnosis is methanol or ethylene glycol poisoning. However, these substances are not typically included in standard toxicology screens, so further testing would be needed to confirm this diagnosis.\n\nDiagnosis: Suspected methanol or ethylene glycol poisoning.""
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}",Suspected methanol or ethylene glycol poisoning,N
10.1056/NEJMcpc2211366,Case 1-2023: A 49-Year-Old Man with Hypokalemia and Paranoia,"Hemoglobin (g/dl)	 	11.4	12.0
Hematocrit (%)	 	33.6	35.6
Platelet count (per μl)	 	231,000	213,000
White-cell count (per μl)	400 ,000	14,630	13,530
Differential count (per μl)			
Neutrophils	 	12,200	12,050
Lymphocytes	 	1670	850
Monocytes	 	330	380
Eosinophils	 	0	0
Basophils	 00	20	30
Sodium (mmol/liter)	 	135	142
Potassium (mmol/liter)	3.6–5.1	2.6	2.2
Chloride (mmol/liter)	98–107	90	94
Carbon dioxide (mmol/liter)	22–32	34	37
Urea nitrogen (mg/dl)	6–20	26	19
Creatinine (mg/dl)	0.60–1.30	0.94	0.87
Glucose (mg/dl)	6 9	221	165
Calcium (mg/dl)	8.9–10.3	8.7	9.2
Magnesium (mg/dl)	 	2.1	2.4
Phosphorus (mg/dl)	2.4–4.7	2.1	1.4
Anion gap (mmol/liter)	 	11	11
Alanine aminotransferase (U/liter)	10–50	202	196
Aspartate aminotransferase (U/liter)	15–41	134	115
Alkaline phosphatase (U/liter)	32–100	505	451
Total bilirubin (mg/dl)	0.0–1.2	1.0	2.0
Globulin (g/dl)	 	3.3	3.4
Albumin (g/dl)	3.5–5.2	2.4	2.4
Ammonia (μmol/liter)	12–48	—	51
C-reactive protein (mg/liter)	0.0–0.8	26.6	—
Erythrocyte sedimentation rate (mm/hr)	 	51	—
Ferritin (μg/liter)	2 00	1058	—
Prothrombin time (sec)	 	13.2	—
International normalized ratio	 	1.0	—
d-dimer (ng/ml)	15 0	3119	—
Fibrinogen (mg/dl)	15 0	465	‚Äö√Ñ√Æ",Cushing‚Äö√Ñ√¥s syndrome due to ectopic secretion of adrenocorticotropic hormone from small-cell lung cancer.,Cushing’s syndrome due to ectopic secretion of adrenocorticotropic hormone from small-cell lung cancer.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 49-year-old man was admitted to this hospital because of hypokalemia and paranoid thoughts.
Six months before the current admission, discomfort on the right side of the chest developed, and the patient was evaluated at another hospital.
Figure 1.

Images Obtained 6 Months before Current Admission.
Dr. Mark C. Murphy: Computed tomography (CT) of the chest (Figure 1), performed after the administration of intravenous contrast material, revealed a nodule in the upper lobe of the left lung that measured 2.1 cm by 1.9 cm, as well as bulky mediastinal and hilar lymphadenopathy.
Dr. Bozym: An endobronchial ultrasound–guided transbronchial needle aspiration of a mediastinal lymph node was performed. Cytologic examination of the specimen revealed small-cell carcinoma.
Five months before the current admission, the patient sought a second opinion in the oncology clinic of this hospital. The patient was counseled about the diagnosis of small-cell lung cancer and the need for additional imaging before consideration of chemotherapy, radiation therapy, or immunotherapy. Additional imaging was scheduled, along with a follow-up appointment. The patient did not undergo additional imaging and did not attend follow-up visits at the oncology clinic of either this hospital or the other hospital.
Six weeks before the current admission, the patient noticed swelling of both legs. Ten days before this admission, the swelling had not abated, and he was evaluated in the emergency department of this hospital.
In the emergency department, the patient described himself as generally healthy and did not report any chronic health conditions. He reported no fever, chills, shortness of breath, or pain. Additional history was obtained from the patient’s brother. The patient had been pursuing alternative treatment for small-cell lung cancer that included a strict diet and intravenous infusions, and he had not shared the diagnosis of small-cell lung cancer with his family until several days earlier. The patient’s brother believed that the patient was in denial about the diagnosis.
When the patient was 12 years of age, he had received a diagnosis of non-Hodgkin’s lymphoma, which had been treated with radiation therapy and splenectomy. Fifteen years before this presentation, ischemic colitis had been treated with small-bowel resection. One year before this presentation, deep-vein thrombosis had been treated with a 4-month course of anticoagulation. There was no history of psychiatric disease. He took no medications and had no known drug allergies; he did not disclose details about the infusions that he had received as alternative treatment for small-cell lung cancer. The patient lived in a suburban area of New England with his parents. He was divorced and frequently visited his children. He worked part-time as a skilled tradesman. Family members reported that he was a lifelong nonsmoker.
Table 1.

Laboratory Data.
The temporal temperature was 36.7°C, the blood pressure 167/95 mm Hg, the pulse 80 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. The patient was alert and appeared well, but he looked thinner than he had looked during his evaluation at the oncology clinic 5 months earlier. The abdomen had a healed surgical scar, and the legs had symmetric 1+ edema. The blood potassium level was 2.6 mmol per liter (reference range, 3.6 to 5.1); the white-cell count was 14,630 per microliter (reference range, 4000 to 11,000). Other laboratory test results are shown in Table 1. Ultrasonography of the legs revealed no evidence of deep-vein thrombosis.
Figure 2.

Images Obtained on Current Admission.
Dr. Murphy: CT pulmonary angiography of the chest (Figure 2A and 2B), performed after the administration of intravenous contrast material, revealed a marked increase in the size of the left-lung mass, which now measured 9.3 cm by 4.6 cm, as well as enlargement of the mediastinal and hilar lymphadenopathy. CT of the abdomen and pelvis (Figure 2C), performed after the administration of intravenous contrast material, showed numerous new ill-defined rim-enhancing hepatic lesions, which measured up to 8.0 cm in diameter; an adrenal mass, which measured 4.1 cm by 3.4 cm; and thrombosis of the branches of the right portal vein. Magnetic resonance imaging (MRI) of the head was normal.
Dr. Bozym: Supplemental potassium was administered intravenously and orally, and the patient was admitted to this hospital. During the next 3 days, additional supplemental potassium was administered. During follow-up interviews, the patient acknowledged the diagnosis of small-cell lung cancer, but he did not explain why he had not shared the diagnosis with his family or provide details about the alternative treatment that he had pursued. On the fourth hospital day, the blood potassium level increased, and the patient asked to go home. He stated that he was willing to attend follow-up visits at the oncology clinic, but he was evasive when chemotherapy and immunotherapy were discussed. The patient was discharged.
One week after discharge, and 1 day before the current admission, the patient’s father accompanied the patient to receive massage therapy and an intravenous infusion as alternative treatment. During the infusion, the patient abruptly became volatile, agitated, and angry. On the drive home, he refused to close the window and stared into the distance. He stated that doctors had cast spells on him during his recent hospitalization and that he had killed his oldest child, which was not true.
The next day, the patient borrowed his brother’s car without permission and drove across the state. After he returned home, family members brought the patient to the emergency department of this hospital for evaluation.
In the emergency department, the patient stated that he was “embarrassed” for being in the hospital. He initially reported no symptoms, but on specific questioning, he acknowledged fatigue, weight loss, generalized weakness, decreased appetite, and ongoing leg swelling. He reported that he did not feel confused, afraid, or worried and that he had no suicidal or homicidal thoughts or auditory or visual hallucinations. Additional history was obtained from the patient’s family members. The patient had not slept for several days. His aggressive and erratic behavior and delusions were not typical, although he could become easily angered and had a long-standing belief that his doctors had administered radiation therapy for non-Hodgkin’s lymphoma to make money.
The temporal temperature was 36.4°C, the blood pressure 194/106 mm Hg, and the pulse 87 beats per minute. The patient alternated between being alert and lethargic, and he could state the names of his children but not their ages. He was cooperative but intermittently paused and stared; he was not distracted by external stimuli, but he seemed to be responding to internal stimuli. He spoke only a couple of words at a time and answered most questions by nodding or shaking his head. There was generalized weakness, which was most pronounced in the proximal muscle groups. The leg edema was unchanged, and the skin appeared abnormally tan; there was no scleral icterus, sublingual jaundice, or asterixis.
The blood potassium level was 2.2 mmol per liter, the carbon dioxide level 37 mmol per liter (reference range, 22 to 32), and the ammonia level 51 μmol per liter (87 μg per deciliter; reference range, 12 to 48 μmol per liter [20 to 82 μg per deciliter]). The white-cell count was 13,530 per microliter. Urinalysis was normal, and urine and blood toxicologic testing was negative. Other laboratory test results are shown in Table 1. CT of the head, performed without the administration of contrast material, was normal. Supplemental potassium was administered intravenously and orally, and the patient was admitted to the hospital. On the second hospital day, the blood potassium level was 2.2 mmol per liter.
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 49-year-old man was admitted to this hospital because of hypokalemia and paranoid thoughts.
Six months before the current admission, discomfort on the right side of the chest developed, and the patient was evaluated at another hospital.
Figure 1.

Images Obtained 6 Months before Current Admission.
Dr. Mark C. Murphy: Computed tomography (CT) of the chest (Figure 1), performed after the administration of intravenous contrast material, revealed a nodule in the upper lobe of the left lung that measured 2.1 cm by 1.9 cm, as well as bulky mediastinal and hilar lymphadenopathy.
Dr. Bozym: An endobronchial ultrasound–guided transbronchial needle aspiration of a mediastinal lymph node was performed. Cytologic examination of the specimen revealed small-cell carcinoma.
Five months before the current admission, the patient sought a second opinion in the oncology clinic of this hospital. The patient was counseled about the diagnosis of small-cell lung cancer and the need for additional imaging before consideration of chemotherapy, radiation therapy, or immunotherapy. Additional imaging was scheduled, along with a follow-up appointment. The patient did not undergo additional imaging and did not attend follow-up visits at the oncology clinic of either this hospital or the other hospital.
Six weeks before the current admission, the patient noticed swelling of both legs. Ten days before this admission, the swelling had not abated, and he was evaluated in the emergency department of this hospital.
In the emergency department, the patient described himself as generally healthy and did not report any chronic health conditions. He reported no fever, chills, shortness of breath, or pain. Additional history was obtained from the patient’s brother. The patient had been pursuing alternative treatment for small-cell lung cancer that included a strict diet and intravenous infusions, and he had not shared the diagnosis of small-cell lung cancer with his family until several days earlier. The patient’s brother believed that the patient was in denial about the diagnosis.
When the patient was 12 years of age, he had received a diagnosis of non-Hodgkin’s lymphoma, which had been treated with radiation therapy and splenectomy. Fifteen years before this presentation, ischemic colitis had been treated with small-bowel resection. One year before this presentation, deep-vein thrombosis had been treated with a 4-month course of anticoagulation. There was no history of psychiatric disease. He took no medications and had no known drug allergies; he did not disclose details about the infusions that he had received as alternative treatment for small-cell lung cancer. The patient lived in a suburban area of New England with his parents. He was divorced and frequently visited his children. He worked part-time as a skilled tradesman. Family members reported that he was a lifelong nonsmoker.
Table 1.

Laboratory Data.
The temporal temperature was 36.7°C, the blood pressure 167/95 mm Hg, the pulse 80 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. The patient was alert and appeared well, but he looked thinner than he had looked during his evaluation at the oncology clinic 5 months earlier. The abdomen had a healed surgical scar, and the legs had symmetric 1+ edema. The blood potassium level was 2.6 mmol per liter (reference range, 3.6 to 5.1); the white-cell count was 14,630 per microliter (reference range, 4000 to 11,000). Other laboratory test results are shown in Table 1. Ultrasonography of the legs revealed no evidence of deep-vein thrombosis.
Figure 2.

Images Obtained on Current Admission.
Dr. Murphy: CT pulmonary angiography of the chest (Figure 2A and 2B), performed after the administration of intravenous contrast material, revealed a marked increase in the size of the left-lung mass, which now measured 9.3 cm by 4.6 cm, as well as enlargement of the mediastinal and hilar lymphadenopathy. CT of the abdomen and pelvis (Figure 2C), performed after the administration of intravenous contrast material, showed numerous new ill-defined rim-enhancing hepatic lesions, which measured up to 8.0 cm in diameter; an adrenal mass, which measured 4.1 cm by 3.4 cm; and thrombosis of the branches of the right portal vein. Magnetic resonance imaging (MRI) of the head was normal.
Dr. Bozym: Supplemental potassium was administered intravenously and orally, and the patient was admitted to this hospital. During the next 3 days, additional supplemental potassium was administered. During follow-up interviews, the patient acknowledged the diagnosis of small-cell lung cancer, but he did not explain why he had not shared the diagnosis with his family or provide details about the alternative treatment that he had pursued. On the fourth hospital day, the blood potassium level increased, and the patient asked to go home. He stated that he was willing to attend follow-up visits at the oncology clinic, but he was evasive when chemotherapy and immunotherapy were discussed. The patient was discharged.
One week after discharge, and 1 day before the current admission, the patient’s father accompanied the patient to receive massage therapy and an intravenous infusion as alternative treatment. During the infusion, the patient abruptly became volatile, agitated, and angry. On the drive home, he refused to close the window and stared into the distance. He stated that doctors had cast spells on him during his recent hospitalization and that he had killed his oldest child, which was not true.
The next day, the patient borrowed his brother’s car without permission and drove across the state. After he returned home, family members brought the patient to the emergency department of this hospital for evaluation.
In the emergency department, the patient stated that he was “embarrassed” for being in the hospital. He initially reported no symptoms, but on specific questioning, he acknowledged fatigue, weight loss, generalized weakness, decreased appetite, and ongoing leg swelling. He reported that he did not feel confused, afraid, or worried and that he had no suicidal or homicidal thoughts or auditory or visual hallucinations. Additional history was obtained from the patient’s family members. The patient had not slept for several days. His aggressive and erratic behavior and delusions were not typical, although he could become easily angered and had a long-standing belief that his doctors had administered radiation therapy for non-Hodgkin’s lymphoma to make money.
The temporal temperature was 36.4°C, the blood pressure 194/106 mm Hg, and the pulse 87 beats per minute. The patient alternated between being alert and lethargic, and he could state the names of his children but not their ages. He was cooperative but intermittently paused and stared; he was not distracted by external stimuli, but he seemed to be responding to internal stimuli. He spoke only a couple of words at a time and answered most questions by nodding or shaking his head. There was generalized weakness, which was most pronounced in the proximal muscle groups. The leg edema was unchanged, and the skin appeared abnormally tan; there was no scleral icterus, sublingual jaundice, or asterixis.
The blood potassium level was 2.2 mmol per liter, the carbon dioxide level 37 mmol per liter (reference range, 22 to 32), and the ammonia level 51 μmol per liter (87 μg per deciliter; reference range, 12 to 48 μmol per liter [20 to 82 μg per deciliter]). The white-cell count was 13,530 per microliter. Urinalysis was normal, and urine and blood toxicologic testing was negative. Other laboratory test results are shown in Table 1. CT of the head, performed without the administration of contrast material, was normal. Supplemental potassium was administered intravenously and orally, and the patient was admitted to the hospital. On the second hospital day, the blood potassium level was 2.2 mmol per liter.
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Paraneoplastic syndrome secondary to small-cell lung cancer. \n\nThe patient's history of small-cell lung cancer, hypokalemia, and psychiatric symptoms suggest a paraneoplastic syndrome. Paraneoplastic syndromes are rare disorders triggered by an altered immune system response to a neoplasm. They are defined as clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease. In this case, the patient's small-cell lung cancer could be causing ectopic production of adrenocorticotropic hormone (ACTH), leading to Cushing's syndrome. This is supported by the patient's hypokalemia, hypernatremia, hypertension, and hyperglycemia, which are common in Cushing's syndrome. The psychiatric symptoms could be due to hypercortisolism, which can cause mood disorders, psychosis, and cognitive impairment.""
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        ""content"": ""Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome due to Small-Cell Lung Cancer. \n\nThe patient has a known diagnosis of small-cell lung cancer, which is known to be associated with paraneoplastic syndromes. The patient's symptoms of hypokalemia, generalized weakness, and hyperpigmentation are suggestive of ectopic ACTH syndrome, a paraneoplastic syndrome where a non-pituitary tumor secretes ACTH, leading to excess cortisol production by the adrenal glands. This results in symptoms of Cushing's syndrome, including hypokalemia, muscle weakness, and hyperpigmentation. The patient's psychiatric symptoms could also be related to hypercortisolism. The lack of response to potassium supplementation suggests an ongoing process causing the hypokalemia, such as ectopic ACTH production.""
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        ""content"": ""The patient is a 49-year-old man with a history of small-cell lung cancer who presents with hypokalemia and paranoid thoughts. The differential diagnosis for this patient includes hyperaldosteronism, Cushing's syndrome, and paraneoplastic syndrome. Hyperaldosteronism and Cushing's syndrome can both cause hypokalemia, but they are less likely in this case because they typically present with hypertension, which this patient does not have. Paraneoplastic syndrome, on the other hand, is a group of rare disorders that are triggered by an altered immune system response to a neoplasm. They are defined as clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease. In this case, the patient's small-cell lung cancer could be causing a paraneoplastic syndrome that is leading to his hypokalemia and psychiatric symptoms. This is supported by the fact that his symptoms have worsened as his cancer has progressed and that he has not responded to potassium supplementation. \n\nDiagnosis: Paraneoplastic syndrome due to small-cell lung cancer.""
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10.1056/NEJMcpc2211360,Case 40-2022: A 38-Year-Old Man with Exertional Chest Discomfort,,Cardiac paraganglioma with a germline mutation in the gene encoding succinate dehydrogenase subunit C (SDHC).,Dopamine-secreting paraganglioma,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 38-year-old man was evaluated at the cardiology clinic of this hospital because of exertional chest discomfort.
The patient had been a competitive athlete in the past and had remained an avid runner. Approximately 15 years before the current evaluation, while he was running, he had episodes of flushing with diffuse cutaneous swelling involving the face, lips, hands, and trunk, along with hives on the abdomen and legs and associated dyspnea. The first episode occurred in autumn and the second episode the following summer. After the second episode, he lost consciousness while sitting on a bench. The next day, he was evaluated at an urgent care center. A Holter monitor was placed, and a transthoracic echocardiogram (TTE) was reportedly normal. The patient consulted with an allergist, who made a diagnosis of food-related exercise-induced anaphylaxis with reactions to soybeans, chickpeas, and tahini, on the basis of the foods he had eaten before these episodes and the results of radioallergosorbent testing. An epinephrine autoinjector was prescribed for use during future episodes, but the anaphylaxis symptoms did not recur.
Approximately 4 months before the current evaluation, during a routine 5-mile jog, the patient had a new sensation that he described as “my heart beating out of my chest.” He rested, and the symptom subsided; he completed his run. One month later, during a bicycle ride, he had “crampy” discomfort in the anterior chest, which abated when he stopped cycling. Two weeks before the current evaluation, during a jog of several miles, he had cramping pain in the anterior chest on the left side that gradually escalated over a 5-minute period. He started walking, and the pain abated; he ran for an additional 20 minutes without a recurrence of pain. He sought an evaluation in the cardiology clinic of this hospital to determine the cause of his symptoms and the safety of continued vigorous exercise.
On evaluation in the cardiology clinic, a review of systems was negative for dyspnea, recent syncope, orthopnea, edema, cough, hemoptysis, and recent allergic symptoms. The patient ran or cycled four times per week and had previously completed a marathon. His medical history included attention deficit–hyperactivity disorder. Five years earlier, an episode of syncope had occurred in the context of multiple episodes of nonbloody diarrhea, abdominal discomfort, and chills. His surgical history included two colonic polypectomies, one 6 years before this evaluation and the other 1 month before this evaluation; pathological examination of the polyps had revealed lymphoid aggregates and hyperplastic polyps. The patient took no medications and reported no adverse reactions to medications.
The patient worked in the financial sector and lived with his wife and children. He did not use tobacco, alcohol, or other substances. Multiple maternal relatives had had colon cancer, and an older brother had had colonic polyps removed in his fourth decade of life. There was a family history of hypertension.
On examination, the blood pressure was 122/84 mm Hg (measured in both arms), the heart rate 54 beats per minute, and the oxygen saturation 99% while the patient was breathing ambient air. There were mild expiratory wheezes; the remainder of the examination was normal.
Figure 1.

Electrocardiograms and Transthoracic Echocardiograms.
An electrocardiogram (ECG) showed sinus bradycardia and anterior T-wave abnormalities, findings that had been observed on tracings obtained 5 years earlier during an evaluation for presyncope; a TTE obtained at that time had been normal. Sinus bradycardia and anterior T-wave abnormalities had not been observed on tracings obtained 15 years earlier (Figure 1A, 1B, and 1C). The white-cell count and platelet count were normal, as were blood levels of hemoglobin, electrolytes, calcium, and thyrotropin and results of renal-function tests. The high-sensitivity troponin level was 10 ng per liter (reference range, 0 to 14). Plasma metanephrines were undetectable, and the normetanephrine level was normal. The next day, a TTE showed no abnormalities of cardiac chamber size and function and no evidence of valvular dysfunction.
An ambulatory patch heart monitor, applied to evaluate cardiac rhythm over a 2-week period, revealed sinus rhythm without arrhythmia. A cardiopulmonary exercise stress test was performed; the patient exercised for 19 minutes 17 seconds according to a treadmill protocol that increased incrementally to maximal effort with a respiratory exchange ratio of 1.12 and a maximum heart rate of 181 beats per minute (99% of the age-predicted maximum). At peak effort, the stress test did not reproduce symptoms, and he stopped because of leg fatigue. An ECG showed 0.5-mm horizontal ST-segment depression in leads III, aVF, V3, and V6, along with isolated premature ventricular contractions. The ventilatory efficiency was normal.
Additional diagnostic testing was performed, and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 38-year-old man was evaluated at the cardiology clinic of this hospital because of exertional chest discomfort.
The patient had been a competitive athlete in the past and had remained an avid runner. Approximately 15 years before the current evaluation, while he was running, he had episodes of flushing with diffuse cutaneous swelling involving the face, lips, hands, and trunk, along with hives on the abdomen and legs and associated dyspnea. The first episode occurred in autumn and the second episode the following summer. After the second episode, he lost consciousness while sitting on a bench. The next day, he was evaluated at an urgent care center. A Holter monitor was placed, and a transthoracic echocardiogram (TTE) was reportedly normal. The patient consulted with an allergist, who made a diagnosis of food-related exercise-induced anaphylaxis with reactions to soybeans, chickpeas, and tahini, on the basis of the foods he had eaten before these episodes and the results of radioallergosorbent testing. An epinephrine autoinjector was prescribed for use during future episodes, but the anaphylaxis symptoms did not recur.
Approximately 4 months before the current evaluation, during a routine 5-mile jog, the patient had a new sensation that he described as “my heart beating out of my chest.” He rested, and the symptom subsided; he completed his run. One month later, during a bicycle ride, he had “crampy” discomfort in the anterior chest, which abated when he stopped cycling. Two weeks before the current evaluation, during a jog of several miles, he had cramping pain in the anterior chest on the left side that gradually escalated over a 5-minute period. He started walking, and the pain abated; he ran for an additional 20 minutes without a recurrence of pain. He sought an evaluation in the cardiology clinic of this hospital to determine the cause of his symptoms and the safety of continued vigorous exercise.
On evaluation in the cardiology clinic, a review of systems was negative for dyspnea, recent syncope, orthopnea, edema, cough, hemoptysis, and recent allergic symptoms. The patient ran or cycled four times per week and had previously completed a marathon. His medical history included attention deficit–hyperactivity disorder. Five years earlier, an episode of syncope had occurred in the context of multiple episodes of nonbloody diarrhea, abdominal discomfort, and chills. His surgical history included two colonic polypectomies, one 6 years before this evaluation and the other 1 month before this evaluation; pathological examination of the polyps had revealed lymphoid aggregates and hyperplastic polyps. The patient took no medications and reported no adverse reactions to medications.
The patient worked in the financial sector and lived with his wife and children. He did not use tobacco, alcohol, or other substances. Multiple maternal relatives had had colon cancer, and an older brother had had colonic polyps removed in his fourth decade of life. There was a family history of hypertension.
On examination, the blood pressure was 122/84 mm Hg (measured in both arms), the heart rate 54 beats per minute, and the oxygen saturation 99% while the patient was breathing ambient air. There were mild expiratory wheezes; the remainder of the examination was normal.
Figure 1.

Electrocardiograms and Transthoracic Echocardiograms.
An electrocardiogram (ECG) showed sinus bradycardia and anterior T-wave abnormalities, findings that had been observed on tracings obtained 5 years earlier during an evaluation for presyncope; a TTE obtained at that time had been normal. Sinus bradycardia and anterior T-wave abnormalities had not been observed on tracings obtained 15 years earlier (Figure 1A, 1B, and 1C). The white-cell count and platelet count were normal, as were blood levels of hemoglobin, electrolytes, calcium, and thyrotropin and results of renal-function tests. The high-sensitivity troponin level was 10 ng per liter (reference range, 0 to 14). Plasma metanephrines were undetectable, and the normetanephrine level was normal. The next day, a TTE showed no abnormalities of cardiac chamber size and function and no evidence of valvular dysfunction.
An ambulatory patch heart monitor, applied to evaluate cardiac rhythm over a 2-week period, revealed sinus rhythm without arrhythmia. A cardiopulmonary exercise stress test was performed; the patient exercised for 19 minutes 17 seconds according to a treadmill protocol that increased incrementally to maximal effort with a respiratory exchange ratio of 1.12 and a maximum heart rate of 181 beats per minute (99% of the age-predicted maximum). At peak effort, the stress test did not reproduce symptoms, and he stopped because of leg fatigue. An ECG showed 0.5-mm horizontal ST-segment depression in leads III, aVF, V3, and V6, along with isolated premature ventricular contractions. The ventilatory efficiency was normal.
Additional diagnostic testing was performed, and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's history of exertional chest discomfort, abnormal ECG findings, and ST-segment depression during a stress test suggest a cardiac origin of his symptoms. The patient's symptoms of chest discomfort that occur with exercise and resolve with rest are consistent with angina, which is most commonly caused by coronary artery disease (CAD). The ST-segment depression observed during the stress test is also indicative of myocardial ischemia, which is most often due to CAD. The patient's history of syncope and his family history of hypertension further support a cardiac etiology. Therefore, the most likely diagnosis is coronary artery disease.""
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        ""content"": ""The patient's symptoms of exertional chest discomfort, history of anaphylaxis, and family history of colon cancer suggest a possible diagnosis of hereditary alpha tryptasemia syndrome (HATS). This condition is characterized by an elevated baseline serum tryptase level and multisystem complaints including flushing, pruritus, gastrointestinal symptoms, and cardiovascular symptoms. The patient's symptoms of chest discomfort during exercise could be due to coronary artery spasm, which can occur in patients with HATS. The patient's history of anaphylaxis and his family history of colon cancer are also consistent with this diagnosis. \n\nHereditary Alpha Tryptasemia Syndrome (HATS)""
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}",Alpha Tryptasemia Syndrome (HATS),N,"{
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        ""content"": ""The patient is a 38-year-old man with a history of exercise-induced anaphylaxis and recent onset of exertional chest discomfort. The differential diagnosis for his symptoms includes coronary artery disease, hypertrophic cardiomyopathy, arrhythmias, and anaphylaxis. Coronary artery disease is less likely given his age, lack of risk factors, and the fact that his symptoms are not consistently provoked by exertion. Hypertrophic cardiomyopathy could present with exertional chest discomfort and syncope, but his echocardiogram was normal, making this diagnosis less likely. Arrhythmias could also cause his symptoms, but his Holter monitor did not show any significant arrhythmias. His history of exercise-induced anaphylaxis could potentially explain his symptoms, but he has not had any recent allergic symptoms. His ECG showed anterior T-wave abnormalities and his stress test showed ST-segment depression and premature ventricular contractions, which could suggest ischemia. However, his troponin level was normal, suggesting that he did not have a recent myocardial infarction. Given his history of exercise-induced anaphylaxis, his symptoms could potentially be due to a variant of this condition known as Kounis syndrome, which is characterized by allergic angina or allergic myocardial infarction. However, this is a rare condition and would not be the most likely explanation for his symptoms. \n\nDiagnosis: Unexplained exertional chest discomfort. Further diagnostic testing is needed to determine the cause.""
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}",Unexplained exertional chest discomfort. Further diagnostic testing is needed to determine the cause,N
10.1056/NEJMcpc2211363,Case 39-2022: A 31-Year-Old Woman with Postpartum Abdominal Pain and Fever,,Hepatic adenoma.,Hepatic adenoma.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 31-year-old woman was admitted to this hospital 15 days after the birth of her first child because of abdominal pain and fever.
The patient had received routine prenatal care at this hospital. Serologic screening during the pregnancy showed immunity to rubella. Rectovaginal culture was positive for group B streptococcus. Tests for syphilis, hepatitis B virus surface antigen, gonorrhea, chlamydia, and human immunodeficiency virus were negative.
Sixteen days before this admission, the patient went into labor at 38 weeks 1 day of gestation. She was admitted to this hospital. The white-cell count was 13,800 per microliter (reference range, 4500 to 11,000), and the hemoglobin level was 14.0 g per deciliter (reference range, 12.0 to 16.0); treatment with intravenous penicillin was started. On hospital day 2, an epidural anesthetic agent was administered. Artificial rupture of the membranes revealed clear, odorless fluid, and infusion of oxytocin was started. Six hours after artificial rupture of the membranes, the patient gave birth to a healthy baby by vaginal delivery. Three minutes later, the placenta was delivered intact. Immediately after delivery, hemorrhage due to uterine atony occurred; there was an estimated blood loss of 500 ml. Bimanual massage of the uterus was performed, and oxytocin and methylergonovine were administered; hemostasis was subsequently achieved. A perineal laceration was repaired. The patient began breast-feeding, and on postpartum day 1, she was discharged.
Six days before the current admission, on postpartum day 9, pain in the left upper quadrant developed. The pain was dull, radiated to the left flank and back, and was worse with movement and deep breathing. The patient presented to a local urgent care clinic; urine was obtained for culture, and empirical treatment with amoxicillin–clavulanate was started.
Five days before this admission, on postpartum day 10, abdominal pain persisted, and a fever with a temporal temperature of 38.3°C developed. The patient sought evaluation in the emergency department of this hospital. She rated the abdominal pain at 10 on a scale of 0 to 10, with 10 indicating the most severe pain. A review of systems was notable for nausea and minimal lochia; there was no diarrhea, constipation, dysuria, hematuria, or breast tenderness.
Table 1.

Laboratory Data.
On examination, the abdomen was soft, and there was mild tenderness on palpation of the left upper quadrant, the uterine fundus, the suprapubic region, and the left costovertebral angle. Pelvic examination, including examination with the use of a speculum, revealed no dehiscence, drainage, or hematoma at the site of the perineal laceration repair and no discharge from the cervical os; there was mild cervical motion tenderness. The white-cell count was 20,700 per microliter. The level of hemoglobin was 11.4 g per deciliter. Blood cultures were obtained. The urine culture obtained at the urgent care clinic was positive for group B streptococcus. Other laboratory test results are shown in Table 1. Treatment with ceftriaxone was started, and the patient was admitted to the hospital for presumed pyelonephritis. On hospital day 3, when the fever and abdominal pain resolved, the patient was discharged home to complete a course of amoxicillin.
During the subsequent 2 days, the patient continued to take amoxicillin at home, but fever and abdominal and flank pain returned. On postpartum day 15, when the pain did not abate after she took acetaminophen, she returned to the emergency department of this hospital.
The patient’s medical history included high-grade cervical dysplasia that had led to a loop electrosurgical excision procedure 5 years earlier, as well as a ruptured ovarian cyst 3 years earlier and nephrolithiasis on the left side 5 months earlier. The patient had not been pregnant before the recent pregnancy; before this pregnancy, she had taken oral contraceptives for 12 years. She took prenatal vitamins, as well as polyethylene glycol, docusate, acetaminophen, and ibuprofen as needed. She had no known drug allergies. She lived with her husband and newborn infant in an urban area of New England and worked as an office manager. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had multiple sclerosis and her father had coronary artery disease; her brother was healthy.
On examination, the abdomen was soft, and there was mild tenderness in the left upper quadrant and at the left costovertebral angle. There was no tenderness on palpation of the uterine fundus or the suprapubic region and no cervical motion tenderness. The white-cell count was 10,330 per microliter. The hemoglobin level was 11.2 g per deciliter, the alanine aminotransferase (ALT) level 153 U per liter (reference range, 7 to 33), the aspartate aminotransferase (AST) level 44 U per liter (reference range, 9 to 32), and the alkaline phosphatase level 194 U per liter (reference range, 30 to 100). Other laboratory test results are shown in Table 1. The patient was admitted to this hospital. The next day, the hemoglobin level decreased to 9.7 g per deciliter.
Additional studies were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 31-year-old woman was admitted to this hospital 15 days after the birth of her first child because of abdominal pain and fever.
The patient had received routine prenatal care at this hospital. Serologic screening during the pregnancy showed immunity to rubella. Rectovaginal culture was positive for group B streptococcus. Tests for syphilis, hepatitis B virus surface antigen, gonorrhea, chlamydia, and human immunodeficiency virus were negative.
Sixteen days before this admission, the patient went into labor at 38 weeks 1 day of gestation. She was admitted to this hospital. The white-cell count was 13,800 per microliter (reference range, 4500 to 11,000), and the hemoglobin level was 14.0 g per deciliter (reference range, 12.0 to 16.0); treatment with intravenous penicillin was started. On hospital day 2, an epidural anesthetic agent was administered. Artificial rupture of the membranes revealed clear, odorless fluid, and infusion of oxytocin was started. Six hours after artificial rupture of the membranes, the patient gave birth to a healthy baby by vaginal delivery. Three minutes later, the placenta was delivered intact. Immediately after delivery, hemorrhage due to uterine atony occurred; there was an estimated blood loss of 500 ml. Bimanual massage of the uterus was performed, and oxytocin and methylergonovine were administered; hemostasis was subsequently achieved. A perineal laceration was repaired. The patient began breast-feeding, and on postpartum day 1, she was discharged.
Six days before the current admission, on postpartum day 9, pain in the left upper quadrant developed. The pain was dull, radiated to the left flank and back, and was worse with movement and deep breathing. The patient presented to a local urgent care clinic; urine was obtained for culture, and empirical treatment with amoxicillin–clavulanate was started.
Five days before this admission, on postpartum day 10, abdominal pain persisted, and a fever with a temporal temperature of 38.3°C developed. The patient sought evaluation in the emergency department of this hospital. She rated the abdominal pain at 10 on a scale of 0 to 10, with 10 indicating the most severe pain. A review of systems was notable for nausea and minimal lochia; there was no diarrhea, constipation, dysuria, hematuria, or breast tenderness.
Table 1.

Laboratory Data.
On examination, the abdomen was soft, and there was mild tenderness on palpation of the left upper quadrant, the uterine fundus, the suprapubic region, and the left costovertebral angle. Pelvic examination, including examination with the use of a speculum, revealed no dehiscence, drainage, or hematoma at the site of the perineal laceration repair and no discharge from the cervical os; there was mild cervical motion tenderness. The white-cell count was 20,700 per microliter. The level of hemoglobin was 11.4 g per deciliter. Blood cultures were obtained. The urine culture obtained at the urgent care clinic was positive for group B streptococcus. Other laboratory test results are shown in Table 1. Treatment with ceftriaxone was started, and the patient was admitted to the hospital for presumed pyelonephritis. On hospital day 3, when the fever and abdominal pain resolved, the patient was discharged home to complete a course of amoxicillin.
During the subsequent 2 days, the patient continued to take amoxicillin at home, but fever and abdominal and flank pain returned. On postpartum day 15, when the pain did not abate after she took acetaminophen, she returned to the emergency department of this hospital.
The patient’s medical history included high-grade cervical dysplasia that had led to a loop electrosurgical excision procedure 5 years earlier, as well as a ruptured ovarian cyst 3 years earlier and nephrolithiasis on the left side 5 months earlier. The patient had not been pregnant before the recent pregnancy; before this pregnancy, she had taken oral contraceptives for 12 years. She took prenatal vitamins, as well as polyethylene glycol, docusate, acetaminophen, and ibuprofen as needed. She had no known drug allergies. She lived with her husband and newborn infant in an urban area of New England and worked as an office manager. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had multiple sclerosis and her father had coronary artery disease; her brother was healthy.
On examination, the abdomen was soft, and there was mild tenderness in the left upper quadrant and at the left costovertebral angle. There was no tenderness on palpation of the uterine fundus or the suprapubic region and no cervical motion tenderness. The white-cell count was 10,330 per microliter. The hemoglobin level was 11.2 g per deciliter, the alanine aminotransferase (ALT) level 153 U per liter (reference range, 7 to 33), the aspartate aminotransferase (AST) level 44 U per liter (reference range, 9 to 32), and the alkaline phosphatase level 194 U per liter (reference range, 30 to 100). Other laboratory test results are shown in Table 1. The patient was admitted to this hospital. The next day, the hemoglobin level decreased to 9.7 g per deciliter.
Additional studies were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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}",Postpartum pyelonephritis and renal abscess,N,"{
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        ""content"": ""This is a 31-year-old woman who presents with abdominal pain and fever 15 days after the birth of her first child. She has a history of group B streptococcus infection during pregnancy, high-grade cervical dysplasia, a ruptured ovarian cyst, and nephrolithiasis. The differential diagnosis for this patient includes postpartum infection, pyelonephritis, endometritis, and septic pelvic thrombophlebitis. The patient's urine culture was positive for group B streptococcus, which is a common cause of urinary tract infections and pyelonephritis. However, her symptoms did not improve with antibiotics, making pyelonephritis less likely. Endometritis is a common cause of fever and abdominal pain in the postpartum period, but the patient's physical examination did not reveal any signs of uterine tenderness, making this diagnosis less likely. Septic pelvic thrombophlebitis is a rare but serious condition that can occur after childbirth. It can cause fever, abdominal pain, and an elevated white blood cell count, all of which this patient has. The patient's symptoms did not improve with antibiotics, which is consistent with septic pelvic thrombophlebitis, as this condition often does not respond to antibiotics alone and requires anticoagulation therapy. \n\nDiagnosis: Septic pelvic thrombophlebitis.""
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}",Septic pelvic thrombophlebitis,N
 10.1056/NEJMcpc2201250,Case 38-2022: A 21-Year-Old Woman with Fatigue and Weight Gain,,Adrenocortical carcinoma.,Cortisol-secreting adrenal adenoma with subclinical Cushing’s syndrome; adrenocortical carcinoma cannot be ruled out.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 21-year-old woman was evaluated at this hospital because of fatigue, weight gain, and abdominal pain.
The patient had been well until 4 months before the current evaluation, when an episode of dull, aching pain in the right lower quadrant occurred. The pain lasted for a few hours before resolving spontaneously. During the next 4 months, episodes of abdominal pain continued to occur and increased in duration, frequency, and severity. The patient sought evaluation in the gynecology clinic of this hospital.
On evaluation, the patient described the pain as variable, rating it between 3 and 8 on a scale of 0 to 10, with 10 indicating the most severe pain. The episodes of pain occurred daily and lasted for up to 20 hours. The pain decreased with sitting or lying down and did not increase with movement; it was not associated with her menstrual period. The patient also reported fatigue, irritability, and weight gain of 4.5 kg in the previous 4 months despite increased exercise and decreased food intake.
There was a history of hypothyroidism, anxiety, irritable bowel syndrome, and migraines. The patient had never been pregnant and had no known history of sexually transmitted infections or abnormal results on screening tests for cervical cancer. She had previously been sexually active with male partners, but she reported no current sexual activity. She had taken oral contraceptives for 2 years but had stopped taking them 6 months before this evaluation, when a levonorgestrel-releasing intrauterine device (IUD) was placed. Other medications included levothyroxine, citalopram, and multivitamins; there were no known drug allergies.
The patient lived with roommates in an urban area of New England. She was a former athlete and worked as a research scientist. She did not smoke cigarettes, drink alcohol, or use illicit drugs. Her family history included hypothyroidism in her mother, coronary artery disease and hyperlipidemia in her father, breast cancer and diabetes in her paternal grandmother, and lung cancer in her paternal grandfather.
On examination, the blood pressure was 119/73 mm Hg and the heart rate 62 beats per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.4. The thyroid was firm on palpation, with a small nodule noted on the right side. The abdomen was nondistended, soft, and nontender. A small hernia with a thrill was noted at the right inguinal ring. A speculum examination of the vagina and cervix was normal; IUD strings were visible at the cervical os. The complete blood count was normal, as were blood levels of electrolytes and glucose and results of tests for kidney, liver, and thyroid function. Screening tests for gonorrhea, chlamydia, human immunodeficiency virus, and syphilis were negative. Imaging studies were obtained.
Figure 1.

Imaging Studies.
Dr. Madeleine Sertic: Transabdominal and transvaginal ultrasonography of the abdomen and pelvis revealed a mass (measuring 4.8 cm by 5.0 cm by 3.9 cm) along the posterior aspect of the right hepatic lobe (Figure 1A). The uterus, ovaries, and adnexa were normal. There was no free fluid in the pelvis, and the IUD was in an appropriate position.
Magnetic resonance imaging of the abdomen, performed before and after the administration of intravenous contrast material, revealed a right adrenal mass (measuring 4.5 cm by 4.7 cm by 4.0 cm) that was T2 isointense (Figure 1B) and T1 hypointense. The mass had diffusion restriction (Figure 1C), as well as early enhancement with washout, which refers to the temporal reduction in the enhancement of a lesion. The features were indeterminate and were not definitively diagnostic of adrenal adenoma or another adrenal lesion, such as pheochromocytoma or adrenocortical carcinoma.
Computed tomography (CT) of the abdomen and pelvis again revealed a right adrenal mass, which had a density of 33 Hounsfield units (HU) before the administration of contrast material (Figure 1D), 74 HU during the portal-venous phase (Figure 1E), and 45 HU during the 15-minute delayed phase (Figure 1F). The absolute washout was calculated as 71%. The absolute washout is calculated by dividing the difference between the portal-venous–phase density and the delayed-phase density by the difference between the portal-venous–phase density and the unenhanced density and then converting the result to a percentage: [(HU portal-venous phase − HU delayed phase) / (HU portal-venous phase − HU unenhanced)] × 100. Adrenal adenomas tend to wash out faster than other adrenal lesions, and an absolute washout of more than 60% is highly suggestive of an adrenal adenoma. However, lesions larger than 4 cm are likely to be malignant, regardless of the washout characteristics.1 There was also a thin-walled cyst (measuring 3.3 cm in diameter) in the lower lobe of the left lung.
Dr. Tran: The patient was referred to the endocrinology clinic of this hospital. Additional laboratory tests were performed to further evaluate the adrenal mass. Blood levels of renin and aldosterone were normal, as were urinary levels of catecholamines and metanephrines. An overnight, low-dose dexamethasone suppression test was performed. The baseline blood corticotropin level was 3 pg per milliliter (0.7 pmol per liter; reference range, 6 to 76 pg per milliliter [1.3 to 16.7 pmol per liter]). At 11 p.m., dexamethasone (1 mg) was administered; at 8 a.m., the blood cortisol level was 9.1 μg per deciliter (251 nmol per liter; reference value, <1.8 μg per deciliter [50 nmol per liter]), and the concurrent blood dexamethasone level was 631 ng per deciliter (reference range, 140 to 295). The 24-hour urinary free cortisol level was 31.0 μg (reference range, 3.5 to 45.0); the blood levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate were normal.
Management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 21-year-old woman was evaluated at this hospital because of fatigue, weight gain, and abdominal pain.
The patient had been well until 4 months before the current evaluation, when an episode of dull, aching pain in the right lower quadrant occurred. The pain lasted for a few hours before resolving spontaneously. During the next 4 months, episodes of abdominal pain continued to occur and increased in duration, frequency, and severity. The patient sought evaluation in the gynecology clinic of this hospital.
On evaluation, the patient described the pain as variable, rating it between 3 and 8 on a scale of 0 to 10, with 10 indicating the most severe pain. The episodes of pain occurred daily and lasted for up to 20 hours. The pain decreased with sitting or lying down and did not increase with movement; it was not associated with her menstrual period. The patient also reported fatigue, irritability, and weight gain of 4.5 kg in the previous 4 months despite increased exercise and decreased food intake.
There was a history of hypothyroidism, anxiety, irritable bowel syndrome, and migraines. The patient had never been pregnant and had no known history of sexually transmitted infections or abnormal results on screening tests for cervical cancer. She had previously been sexually active with male partners, but she reported no current sexual activity. She had taken oral contraceptives for 2 years but had stopped taking them 6 months before this evaluation, when a levonorgestrel-releasing intrauterine device (IUD) was placed. Other medications included levothyroxine, citalopram, and multivitamins; there were no known drug allergies.
The patient lived with roommates in an urban area of New England. She was a former athlete and worked as a research scientist. She did not smoke cigarettes, drink alcohol, or use illicit drugs. Her family history included hypothyroidism in her mother, coronary artery disease and hyperlipidemia in her father, breast cancer and diabetes in her paternal grandmother, and lung cancer in her paternal grandfather.
On examination, the blood pressure was 119/73 mm Hg and the heart rate 62 beats per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.4. The thyroid was firm on palpation, with a small nodule noted on the right side. The abdomen was nondistended, soft, and nontender. A small hernia with a thrill was noted at the right inguinal ring. A speculum examination of the vagina and cervix was normal; IUD strings were visible at the cervical os. The complete blood count was normal, as were blood levels of electrolytes and glucose and results of tests for kidney, liver, and thyroid function. Screening tests for gonorrhea, chlamydia, human immunodeficiency virus, and syphilis were negative. Imaging studies were obtained.
Figure 1.

Imaging Studies.
Dr. Madeleine Sertic: Transabdominal and transvaginal ultrasonography of the abdomen and pelvis revealed a mass (measuring 4.8 cm by 5.0 cm by 3.9 cm) along the posterior aspect of the right hepatic lobe (Figure 1A). The uterus, ovaries, and adnexa were normal. There was no free fluid in the pelvis, and the IUD was in an appropriate position.
Magnetic resonance imaging of the abdomen, performed before and after the administration of intravenous contrast material, revealed a right adrenal mass (measuring 4.5 cm by 4.7 cm by 4.0 cm) that was T2 isointense (Figure 1B) and T1 hypointense. The mass had diffusion restriction (Figure 1C), as well as early enhancement with washout, which refers to the temporal reduction in the enhancement of a lesion. The features were indeterminate and were not definitively diagnostic of adrenal adenoma or another adrenal lesion, such as pheochromocytoma or adrenocortical carcinoma.
Computed tomography (CT) of the abdomen and pelvis again revealed a right adrenal mass, which had a density of 33 Hounsfield units (HU) before the administration of contrast material (Figure 1D), 74 HU during the portal-venous phase (Figure 1E), and 45 HU during the 15-minute delayed phase (Figure 1F). The absolute washout was calculated as 71%. The absolute washout is calculated by dividing the difference between the portal-venous–phase density and the delayed-phase density by the difference between the portal-venous–phase density and the unenhanced density and then converting the result to a percentage: [(HU portal-venous phase − HU delayed phase) / (HU portal-venous phase − HU unenhanced)] × 100. Adrenal adenomas tend to wash out faster than other adrenal lesions, and an absolute washout of more than 60% is highly suggestive of an adrenal adenoma. However, lesions larger than 4 cm are likely to be malignant, regardless of the washout characteristics.1 There was also a thin-walled cyst (measuring 3.3 cm in diameter) in the lower lobe of the left lung.
Dr. Tran: The patient was referred to the endocrinology clinic of this hospital. Additional laboratory tests were performed to further evaluate the adrenal mass. Blood levels of renin and aldosterone were normal, as were urinary levels of catecholamines and metanephrines. An overnight, low-dose dexamethasone suppression test was performed. The baseline blood corticotropin level was 3 pg per milliliter (0.7 pmol per liter; reference range, 6 to 76 pg per milliliter [1.3 to 16.7 pmol per liter]). At 11 p.m., dexamethasone (1 mg) was administered; at 8 a.m., the blood cortisol level was 9.1 μg per deciliter (251 nmol per liter; reference value, <1.8 μg per deciliter [50 nmol per liter]), and the concurrent blood dexamethasone level was 631 ng per deciliter (reference range, 140 to 295). The 24-hour urinary free cortisol level was 31.0 μg (reference range, 3.5 to 45.0); the blood levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate were normal.
Management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Cushing's Syndrome due to adrenal adenoma. \n\nThe patient's symptoms of weight gain, fatigue, and irritability, along with her history of hypothyroidism, suggest an endocrine disorder. The discovery of a right adrenal mass on imaging studies further supports this. The mass was found to have early enhancement with washout, which is characteristic of an adrenal adenoma. However, the size of the mass (larger than 4 cm) suggests it could be malignant. The results of the dexamethasone suppression test, in which the cortisol level remained high despite the administration of dexamethasone, indicate that the patient has Cushing's syndrome, a condition characterized by excessive cortisol production. The location of the mass in the adrenal gland suggests that this is the source of the excess cortisol, leading to the diagnosis of Cushing's syndrome due to an adrenal adenoma.""
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        ""content"": ""Cushing's syndrome due to adrenal adenoma. \n\nThe patient's symptoms of weight gain, fatigue, and irritability, along with her history of hypothyroidism, suggest an endocrine disorder. The imaging studies revealed a right adrenal mass, which could be an adrenal adenoma, pheochromocytoma, or adrenocortical carcinoma. The results of the dexamethasone suppression test, which showed a high blood cortisol level, suggest Cushing's syndrome, a condition caused by prolonged exposure to high levels of cortisol. The adrenal mass is likely an adenoma, a benign tumor that can produce excess cortisol, leading to Cushing's syndrome.""
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        ""content"": ""The patient is a 21-year-old woman presenting with fatigue, weight gain, and abdominal pain. She has a history of hypothyroidism, anxiety, irritable bowel syndrome, and migraines. She has a levonorgestrel-releasing intrauterine device (IUD) and is not currently sexually active. She has a firm thyroid with a small nodule on the right side and a small hernia with a thrill at the right inguinal ring. Imaging studies reveal a right adrenal mass and a thin-walled cyst in the lower lobe of the left lung. Blood levels of renin and aldosterone are normal, as are urinary levels of catecholamines and metanephrines. An overnight, low-dose dexamethasone suppression test shows a blood cortisol level of 9.1 \u03bcg per deciliter and a concurrent blood dexamethasone level of 631 ng per deciliter. The 24-hour urinary free cortisol level is 31.0 \u03bcg and the blood levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate are normal.\n\nThe differential diagnosis for this patient includes adrenal adenoma, pheochromocytoma, adrenocortical carcinoma, and Cushing's syndrome. The patient's symptoms of fatigue, weight gain, and abdominal pain could be consistent with any of these conditions. However, the patient's normal levels of renin, aldosterone, catecholamines, and metanephrines make pheochromocytoma and adrenocortical carcinoma less likely. The patient's adrenal mass and the results of the dexamethasone suppression test suggest that the patient may have Cushing's syndrome. However, the patient's normal 24-hour urinary free cortisol level and the lack of other typical symptoms of Cushing's syndrome such as purple striae, easy bruising, and muscle weakness make this diagnosis less likely. The patient's adrenal mass, the results of the dexamethasone suppression test, and the imaging findings are most consistent with an adrenal adenoma.\n\nDiagnosis: Adrenal adenoma.""
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}",Adrenal adenoma,N
10.1056/NEJMcpc2211357,"Case 37-2022: A 55-Year-Old Man with Fatigue, Weight Loss, and Pulmonary Nodules","White-cell count (per μl)	 	7490	3570
Differential count (per μl)			
Neutrophils	 	6880	3380
Lymphocytes	100–4800	190	120
Monocytes	 	300	60
Eosinophils	 	10	—
Basophils	 00	20	—
Sodium (mmol/liter)	 	133	132
Potassium (mmol/liter)	 	4.5	5.4
Chloride (mmol/liter)	 	93	95
Carbon dioxide (mmol/liter)	 	17	15
Urea nitrogen (mg/dl)	 	33	95
Creatinine (mg/dl)	 	2.31	5.05
Glucose (mg/dl)	74–106	111	102
Calcium (mg/dl)	 	10.1	13.1
Phosphorus (mg/dl)	 	3.0	5.1
Lactic acid (mmol/liter)	 	—	4.4
Alanine aminotransferase (U/liter)	 	—	44
Aspartate aminotransferase (U/liter)	 	—	79
Alkaline phosphatase (U/liter)	 	—	171
Total bilirubin (mg/dl)	0–1.0	—	0.6
Globulin (g/dl)	 	—	3.3
Albumin (g/dl)	 	3.5	2.8
Hemoglobin (g/dl)	 	7.8	6.6
Hematocrit (%)	 	26.0	23.6
Platelet count (per μl)	 	185,000	144,000
Prothrombin time (sec)	 	15.0	15.8
International normalized ratio	 	1.2	1.3
Activated partial-thromboplastin time (sec)	22. 5.0	54.4	—
Urine			
Bilirubin	Negative	—	Negative
Urobilinogen	Negative	—	Negative
Blood	Negative	—	1+
Glucose	Negative	—	Negative
Ketones	Negative	—	Negative
Leukocyte esterase	Negative	—	Negative
Nitrite	Negative	—	Negative",Disseminated Mycobacterium tuberculosis infection.,Mycobacterium tuberculosis infection (most likely donor-derived infection).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 55-year-old man was admitted to this hospital 7 months after kidney transplantation because of fatigue, weight loss, and new pulmonary nodules.
The patient had been in his usual state of health until 1 week before this admission, when severe fatigue and generalized weakness developed. He had lost 4.5 kg in the past month after making healthier dietary choices; however, he had also noticed abdominal discomfort and a decrease in appetite.
During the next week, the patient was able to eat and drink very little and lost an additional 4.5 kg. The fatigue and weakness worsened, and he mostly stayed in bed. He had several episodes of lightheadedness, gait instability, and falls while he was walking to the bathroom. There was new odynophagia, dysphagia, and nausea.
On the day of admission, the patient was evaluated at the transplant nephrology clinic of this hospital before a scheduled infusion of belatacept. The temperature was 37.3°C, the blood pressure 70/50 mm Hg, the heart rate 98 beats per minute, the respiratory rate 35 breaths per minute, and the oxygen saturation 96% while he was breathing ambient air. He appeared cachectic and lethargic. He was transported by ambulance from the clinic to the emergency department of this hospital.
In the emergency department, the patient reported malaise and feeling like he had no energy or strength. The lightheadedness and gait instability persisted. A review of systems was notable for shortness of breath, dark urine, and continued anorexia, nausea, odynophagia, dysphagia, and abdominal discomfort. He reported no chills, night sweats, cough, chest pain, vomiting, hematochezia, melena, or dysuria.
The patient had a history of sarcoidosis. Nine years before this admission, nephrocalcinosis caused end-stage kidney disease. Hemodialysis was started, and this treatment was continued until a deceased-donor kidney transplantation was performed 7 months before this admission. Routine serologic testing performed before transplantation was positive for Epstein–Barr virus (EBV) IgG and cytomegalovirus (CMV) IgG. An interferon-γ release assay for Mycobacterium tuberculosis was negative. Serologic testing in the donor was also positive for EBV IgG but was negative for CMV IgG. Induction immunosuppressive therapy with antithymocyte globulin was initiated; maintenance therapy included prednisone, mycophenolate mofetil, and tacrolimus.
Six months before the current admission, pathological examination of a biopsy specimen from the transplanted kidney revealed vascular disease of donor origin and acute tubular injury but no evidence of T-cell–mediated or antibody-mediated rejection. Treatment with tacrolimus was stopped and belatacept started; prednisone and mycophenolate mofetil therapy was continued.
One month before the current admission, pathological examination of another biopsy specimen from the transplanted kidney revealed focal infiltrates that were vaguely granulomatous and were associated with ruptured tubules and interstitial Tamm–Horsfall protein (also known as uromodulin). There was no evidence of allograft rejection.
Table 1.

Laboratory Data.
Two weeks before the current admission, laboratory tests revealed a blood creatinine level of 2.31 mg per deciliter (204.2 μmol per liter; reference range, 0.60 to 1.50 mg per deciliter [53.0 to 132.6 μmol per liter]); routine laboratory tests had revealed similar creatinine levels during the previous 6 months. Other laboratory test results are shown in Table 1.
The patient also had a history of hypertension, hyperlipidemia, and gout. Current medications included aspirin, atorvastatin, labetalol, nifedipine, trimethoprim–sulfamethoxazole, valganciclovir, prednisone, mycophenolate mofetil, and belatacept. There were no known drug allergies. The patient lived with his mother in an urban area of New England and had never traveled outside the region. He worked as an administrator and had never been homeless or incarcerated. He had no sexual partners and did not smoke tobacco, use illicit drugs, or drink alcohol.
On the day of evaluation in the emergency department, the temperature was 36.7°C, the blood pressure 80/50 mm Hg, the heart rate 100 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 92% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 20.5. The patient was lethargic and spoke in sentences of three or four words. The mucous membranes were dry, and the throat could not be evaluated because of nausea. There was no cervical lymphadenopathy. Auscultation of the lungs revealed diffuse inspiratory crackles. Neurologic examination was limited but was notable for 4/5 motor strength in the arms and legs.
The blood level of creatinine was 5.05 mg per deciliter (446.4 μmol per liter), the calcium level 13.1 mg per deciliter (3.3 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter [2.1 to 2.6 mmol per liter]), the lactic acid level 4.4 mmol per liter (39.6 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter [4.5 to 18.0 mg per deciliter]), and the hemoglobin level 6.6 g per deciliter (reference range, 13.5 to 17.5). Cultures of blood were obtained. Other laboratory test results are shown in Table 1.
Figure 1.

Imaging Studies of the Chest Obtained on Admission.
Figure 2.

CT of the Abdomen and Spleen.
Dr. Mark C. Murphy: Computed tomography (CT) of the chest, abdomen, and pelvis was performed without the administration of intravenous contrast material. CT of the chest (Figure 1) revealed innumerable bilateral miliary pulmonary nodules that were new relative to a CT scan that had been obtained 6 months earlier. The nodules were in a random distribution that was suggestive of a hematogenous origin. Trace bilateral pleural effusions were present, as was calcified mediastinal and bilateral hilar lymphadenopathy; the lymphadenopathy appeared unchanged from previous imaging. CT of the spleen (Figure 2) revealed new splenomegaly. There was new mild dilatation of the renal collecting system of the transplanted kidney in the right lower quadrant of the abdomen.
Dr. Lee: While the patient was being evaluated in the emergency department, the temperature increased to 39.6°C. Intravenous fluids and intravenous infusion of phenylephrine were administered. Empirical treatment with vancomycin, cefepime, metronidazole, levofloxacin, doxycycline, and micafungin was started; trimethoprim–sulfamethoxazole and valganciclovir were continued. Treatment with prednisone and mycophenolate mofetil was discontinued, and hydrocortisone therapy was started. The patient was admitted to the intensive care unit.
Within 24 hours after admission, the oxygen saturation had decreased to 84% while the patient was breathing ambient air; supplemental oxygen was administered through a nasal cannula at a rate of 2 liters per minute, and the oxygen saturation increased to 94%. Continuous intravenous infusion of phenylephrine was continued, and norepinephrine was added to maintain a mean arterial blood pressure above 65 mm Hg. Two units of packed red cells were transfused. The creatinine level decreased to 3.82 mg per deciliter (337.7 μmol per liter), the lactic acid level to 1.6 mmol per liter (14.4 mg per deciliter), and the calcium level to 8.9 mg per deciliter (2.2 mmol per liter). Treatment with levofloxacin and micafungin was stopped; isavuconazole was started.
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 55-year-old man was admitted to this hospital 7 months after kidney transplantation because of fatigue, weight loss, and new pulmonary nodules.
The patient had been in his usual state of health until 1 week before this admission, when severe fatigue and generalized weakness developed. He had lost 4.5 kg in the past month after making healthier dietary choices; however, he had also noticed abdominal discomfort and a decrease in appetite.
During the next week, the patient was able to eat and drink very little and lost an additional 4.5 kg. The fatigue and weakness worsened, and he mostly stayed in bed. He had several episodes of lightheadedness, gait instability, and falls while he was walking to the bathroom. There was new odynophagia, dysphagia, and nausea.
On the day of admission, the patient was evaluated at the transplant nephrology clinic of this hospital before a scheduled infusion of belatacept. The temperature was 37.3°C, the blood pressure 70/50 mm Hg, the heart rate 98 beats per minute, the respiratory rate 35 breaths per minute, and the oxygen saturation 96% while he was breathing ambient air. He appeared cachectic and lethargic. He was transported by ambulance from the clinic to the emergency department of this hospital.
In the emergency department, the patient reported malaise and feeling like he had no energy or strength. The lightheadedness and gait instability persisted. A review of systems was notable for shortness of breath, dark urine, and continued anorexia, nausea, odynophagia, dysphagia, and abdominal discomfort. He reported no chills, night sweats, cough, chest pain, vomiting, hematochezia, melena, or dysuria.
The patient had a history of sarcoidosis. Nine years before this admission, nephrocalcinosis caused end-stage kidney disease. Hemodialysis was started, and this treatment was continued until a deceased-donor kidney transplantation was performed 7 months before this admission. Routine serologic testing performed before transplantation was positive for Epstein–Barr virus (EBV) IgG and cytomegalovirus (CMV) IgG. An interferon-γ release assay for Mycobacterium tuberculosis was negative. Serologic testing in the donor was also positive for EBV IgG but was negative for CMV IgG. Induction immunosuppressive therapy with antithymocyte globulin was initiated; maintenance therapy included prednisone, mycophenolate mofetil, and tacrolimus.
Six months before the current admission, pathological examination of a biopsy specimen from the transplanted kidney revealed vascular disease of donor origin and acute tubular injury but no evidence of T-cell–mediated or antibody-mediated rejection. Treatment with tacrolimus was stopped and belatacept started; prednisone and mycophenolate mofetil therapy was continued.
One month before the current admission, pathological examination of another biopsy specimen from the transplanted kidney revealed focal infiltrates that were vaguely granulomatous and were associated with ruptured tubules and interstitial Tamm–Horsfall protein (also known as uromodulin). There was no evidence of allograft rejection.
Table 1.

Laboratory Data.
Two weeks before the current admission, laboratory tests revealed a blood creatinine level of 2.31 mg per deciliter (204.2 μmol per liter; reference range, 0.60 to 1.50 mg per deciliter [53.0 to 132.6 μmol per liter]); routine laboratory tests had revealed similar creatinine levels during the previous 6 months. Other laboratory test results are shown in Table 1.
The patient also had a history of hypertension, hyperlipidemia, and gout. Current medications included aspirin, atorvastatin, labetalol, nifedipine, trimethoprim–sulfamethoxazole, valganciclovir, prednisone, mycophenolate mofetil, and belatacept. There were no known drug allergies. The patient lived with his mother in an urban area of New England and had never traveled outside the region. He worked as an administrator and had never been homeless or incarcerated. He had no sexual partners and did not smoke tobacco, use illicit drugs, or drink alcohol.
On the day of evaluation in the emergency department, the temperature was 36.7°C, the blood pressure 80/50 mm Hg, the heart rate 100 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 92% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 20.5. The patient was lethargic and spoke in sentences of three or four words. The mucous membranes were dry, and the throat could not be evaluated because of nausea. There was no cervical lymphadenopathy. Auscultation of the lungs revealed diffuse inspiratory crackles. Neurologic examination was limited but was notable for 4/5 motor strength in the arms and legs.
The blood level of creatinine was 5.05 mg per deciliter (446.4 μmol per liter), the calcium level 13.1 mg per deciliter (3.3 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter [2.1 to 2.6 mmol per liter]), the lactic acid level 4.4 mmol per liter (39.6 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter [4.5 to 18.0 mg per deciliter]), and the hemoglobin level 6.6 g per deciliter (reference range, 13.5 to 17.5). Cultures of blood were obtained. Other laboratory test results are shown in Table 1.
Figure 1.

Imaging Studies of the Chest Obtained on Admission.
Figure 2.

CT of the Abdomen and Spleen.
Dr. Mark C. Murphy: Computed tomography (CT) of the chest, abdomen, and pelvis was performed without the administration of intravenous contrast material. CT of the chest (Figure 1) revealed innumerable bilateral miliary pulmonary nodules that were new relative to a CT scan that had been obtained 6 months earlier. The nodules were in a random distribution that was suggestive of a hematogenous origin. Trace bilateral pleural effusions were present, as was calcified mediastinal and bilateral hilar lymphadenopathy; the lymphadenopathy appeared unchanged from previous imaging. CT of the spleen (Figure 2) revealed new splenomegaly. There was new mild dilatation of the renal collecting system of the transplanted kidney in the right lower quadrant of the abdomen.
Dr. Lee: While the patient was being evaluated in the emergency department, the temperature increased to 39.6°C. Intravenous fluids and intravenous infusion of phenylephrine were administered. Empirical treatment with vancomycin, cefepime, metronidazole, levofloxacin, doxycycline, and micafungin was started; trimethoprim–sulfamethoxazole and valganciclovir were continued. Treatment with prednisone and mycophenolate mofetil was discontinued, and hydrocortisone therapy was started. The patient was admitted to the intensive care unit.
Within 24 hours after admission, the oxygen saturation had decreased to 84% while the patient was breathing ambient air; supplemental oxygen was administered through a nasal cannula at a rate of 2 liters per minute, and the oxygen saturation increased to 94%. Continuous intravenous infusion of phenylephrine was continued, and norepinephrine was added to maintain a mean arterial blood pressure above 65 mm Hg. Two units of packed red cells were transfused. The creatinine level decreased to 3.82 mg per deciliter (337.7 μmol per liter), the lactic acid level to 1.6 mmol per liter (14.4 mg per deciliter), and the calcium level to 8.9 mg per deciliter (2.2 mmol per liter). Treatment with levofloxacin and micafungin was stopped; isavuconazole was started.
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 55-year-old man who had a kidney transplant 7 months ago and is now presenting with fatigue, weight loss, and new pulmonary nodules. He has a history of sarcoidosis and end-stage kidney disease. His symptoms include severe fatigue, generalized weakness, abdominal discomfort, decrease in appetite, lightheadedness, gait instability, falls, odynophagia, dysphagia, and nausea. He also has shortness of breath, dark urine, and continued anorexia. His lab results show an elevated creatinine level and calcium level. His CT scan shows innumerable bilateral miliary pulmonary nodules, trace bilateral pleural effusions, calcified mediastinal and bilateral hilar lymphadenopathy, and new splenomegaly. These findings suggest a systemic disease that is affecting multiple organs. Given his history of sarcoidosis and the presence of non-caseating granulomas on biopsy, the most likely diagnosis is a flare of his sarcoidosis, possibly exacerbated by his immunosuppressive therapy following kidney transplantation.\n\nDiagnosis: Sarcoidosis flare.""
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        ""content"": ""This is a 55-year-old man with a history of kidney transplantation who presents with fatigue, weight loss, and new pulmonary nodules. His symptoms include severe fatigue, generalized weakness, abdominal discomfort, decrease in appetite, odynophagia, dysphagia, and nausea. He also has a history of sarcoidosis. The differential diagnosis for this patient includes infection, malignancy, and recurrence of sarcoidosis. Given his history of kidney transplantation, he is immunosuppressed and at risk for opportunistic infections. His symptoms of fatigue, weight loss, and new pulmonary nodules could be due to an infection such as tuberculosis, fungal infection, or a viral infection such as CMV or EBV. His symptoms could also be due to a malignancy such as post-transplant lymphoproliferative disorder (PTLD), which can occur in transplant patients and is often associated with EBV infection. His history of sarcoidosis could also be a factor, as sarcoidosis can recur after transplantation. The presence of miliary nodules on CT scan is suggestive of a hematogenous spread of infection or malignancy. The patient's history of positive EBV IgG and CMV IgG before transplantation raises the possibility of reactivation of these viruses due to immunosuppression. The absence of gastrointestinal symptoms makes CMV less likely. The presence of vaguely granulomatous infiltrates on kidney biopsy one month prior to admission could suggest a recurrence of sarcoidosis, but could also be seen in tuberculosis or fungal infections. Given the patient's immunosuppressed state, the presence of miliary nodules on imaging, and the granulomatous infiltrates on kidney biopsy, an infectious etiology seems most likely.\n\nDiagnosis: Disseminated tuberculosis or fungal infection in a post-transplant patient.""
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10.1056/NEJMcpc2211355,Case 36-2022: A 30-Year-Old Woman with Decreased Vision and Headache,,"Meningioma, meningothelial type, World Health Organization grade 1.","Optic nerve tumor, either optic nerve sheath meningioma or optic nerve glioma.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 30-year-old woman was evaluated in the neuro-ophthalmology clinic at a hospital affiliated with this hospital because of monocular vision loss.
Two months before the current presentation, during the third trimester of the patient’s first pregnancy, headache and decreased vision in the right eye developed. The patient thought that the headache felt like previous migraines, which had been infrequent. However, decreased vision had not been a typical feature of her migraines. Colors appeared dim, and light perception was decreased. There was soreness in the right eye but no pain with eye movement.
Five days later, the patient was evaluated by an optometrist. She reported that she could see only shapes and movements. On a visual field test, there was a normal response in the left eye but no response in the right eye. The patient was instructed to seek evaluation in an emergency department of another hospital.
In the emergency department, magnetic resonance imaging (MRI) of the head, which was performed without the administration of intravenous contrast material because of the pregnancy, revealed marked enlargement of the intraorbital right optic nerve. The nerve appeared isointense as compared with the extraocular muscles on the T1-weighted sequences but appeared bright on the T2-weighted sequence; the globes appeared normal, and the extraocular muscles were not enlarged. The results of magnetic resonance venography of the head were normal.
The patient was admitted to the hospital, and treatment with intravenous methylprednisolone was initiated for a working diagnosis of optic neuritis. During the hospitalization, her ability to see colors improved slightly, but her vision did not improve; she could see only hand motions. On the fifth hospital day, she was discharged home with instructions to schedule follow-up appointments with a neurologist and an optometrist.
One month after discharge from the other hospital and 2 weeks before the current presentation, the patient was again evaluated by her optometrist. The vision in the right eye had worsened; she was no longer able to see shadows or movements. The patient was referred for evaluation by a neuro-ophthalmologist.
On the current presentation to the neuro-ophthalmology clinic of a hospital affiliated with this hospital, the patient reported no improvement in vision and ongoing soreness in the right eye. There was a history of Lyme disease, which had been diagnosed during the second trimester of pregnancy and had been treated with amoxicillin. Medications included prenatal vitamins and ferrous sulfate. The patient lived with her husband in New England and worked in health care. She had never smoked tobacco and did not drink alcohol or use illicit drugs. A brother had a history of childhood epilepsy, and her mother had macular degeneration.
Figure 1.

Funduscopic Images.
On examination, the visual acuity was 20/15 in the left eye, and there was no light perception in the right eye. The pupils were symmetric and reactive to light, although the response in the right pupil was sluggish; an afferent pupillary defect was present in the right eye. On the Ishihara color test, all plates were identified with the left eye. On a visual field test, there was a normal response in the left eye. The Ishihara color test and the visual field test could not be performed on the right eye because of poor vision. The results of a slit-lamp examination were normal, with no cells identified in the anterior chamber or vitreous. On a funduscopic examination (Figure 1A and 1B), the optic disk in the right eye was swollen and had temporal pallor; there was a small area of hypopigmentation close to the macula in the left eye. Optical coherence tomography revealed increased thickness of the retinal nerve fiber layer and circumferential thinning of the ganglion cell complex of the right eye; no abnormalities were noted in the left eye.
The blood creatinine level was 0.56 mg per deciliter (50 μmol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 μmol per liter]) and the blood alkaline phosphatase level 147 U per liter (reference range, 30 to 100). The results of other kidney-function and liver-function tests were normal, as were the blood levels of electrolytes, the complete blood count, and the results of coagulation tests. The blood C-reactive protein level was 15 mg per liter (reference value,  ) and the erythrocyte sedimentation rate 34 mm per hour (reference range, 0 to 20). A blood test for antinuclear antibodies was positive at a titer of 1:40 with a speckled pattern. Tests for antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) were negative. A diagnosis of atypical optic neuritis was considered. Because the patient was near delivery, further treatment was delayed until after the birth of her child, which occurred 3 days later.
Six days after delivery of the baby, the patient was admitted to this hospital, and additional studies were obtained. Lumbar puncture was performed. On cerebrospinal fluid (CSF) analysis, there were no nucleated cells, and the levels of protein, glucose, albumin, and IgG were normal. There was no oligoclonal banding after concentration of the CSF. Testing of the CSF was negative for syphilis antibodies and for antibodies against aquaporin-4.
Figure 2.

MRI of the Head.
Dr. Benjamin M. Kozak: MRI of the head (Figure 2), performed before and after the administration of intravenous contrast material, revealed prominent fusiform enlargement of a segment of the intraorbital right optic nerve with associated enhancement, as well as associated hyperintensity on the T2-weighted short-tau inversion recovery (STIR) sequence. There was no evidence of associated orbital edema or other orbital abnormalities. There was a punctate hyperintense focus within the left parietal subcortical white matter on the T2-weighted fluid-attenuated inversion recovery sequence, without associated enhancement or restricted diffusion.
Dr. Chwalisz: Treatment with intravenous methylprednisolone and daily plasmapheresis was administered. On the fourth hospital day, the soreness in the right eye had resolved, and there was light perception in the right eye. On the fifth hospital day, treatment with intravenous methylprednisolone was changed to oral prednisone. On the ninth hospital day, rituximab was administered, and the patient was discharged home with a prescription for a 7-week tapering course of prednisone.
During the next 3 weeks, treatment with rituximab was administered weekly. Two weeks after the last rituximab infusion, the patient was evaluated in the neuro-ophthalmology clinic at the hospital affiliated with this hospital. She reported no eye pain and only occasional headache, but she noted that the vision in the right eye had worsened. Examination revealed no light perception in the right eye, with an afferent pupillary defect. The results of a visual field test and the Ishihara color test were unchanged from the previous evaluation in the neuro-ophthalmology clinic. On a funduscopic examination (Figure 1C), the optic disk in the right eye was swollen and had more pronounced temporal pallor; optociliary shunt vessels were also newly present. Additional imaging studies were obtained.
Dr. Kozak: Follow-up MRI of the head (Figure 2) revealed no radiologically significant change in the segmental enlargement of the intraorbital right optic nerve, with persistent enhancement as well as hyperintensity on the T2-weighted STIR sequence. No new orbital abnormalities were present. In addition, the punctate lesion in the left parietal subcortical white matter was unchanged.
Dr. Chwalisz: A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 30-year-old woman was evaluated in the neuro-ophthalmology clinic at a hospital affiliated with this hospital because of monocular vision loss.
Two months before the current presentation, during the third trimester of the patient’s first pregnancy, headache and decreased vision in the right eye developed. The patient thought that the headache felt like previous migraines, which had been infrequent. However, decreased vision had not been a typical feature of her migraines. Colors appeared dim, and light perception was decreased. There was soreness in the right eye but no pain with eye movement.
Five days later, the patient was evaluated by an optometrist. She reported that she could see only shapes and movements. On a visual field test, there was a normal response in the left eye but no response in the right eye. The patient was instructed to seek evaluation in an emergency department of another hospital.
In the emergency department, magnetic resonance imaging (MRI) of the head, which was performed without the administration of intravenous contrast material because of the pregnancy, revealed marked enlargement of the intraorbital right optic nerve. The nerve appeared isointense as compared with the extraocular muscles on the T1-weighted sequences but appeared bright on the T2-weighted sequence; the globes appeared normal, and the extraocular muscles were not enlarged. The results of magnetic resonance venography of the head were normal.
The patient was admitted to the hospital, and treatment with intravenous methylprednisolone was initiated for a working diagnosis of optic neuritis. During the hospitalization, her ability to see colors improved slightly, but her vision did not improve; she could see only hand motions. On the fifth hospital day, she was discharged home with instructions to schedule follow-up appointments with a neurologist and an optometrist.
One month after discharge from the other hospital and 2 weeks before the current presentation, the patient was again evaluated by her optometrist. The vision in the right eye had worsened; she was no longer able to see shadows or movements. The patient was referred for evaluation by a neuro-ophthalmologist.
On the current presentation to the neuro-ophthalmology clinic of a hospital affiliated with this hospital, the patient reported no improvement in vision and ongoing soreness in the right eye. There was a history of Lyme disease, which had been diagnosed during the second trimester of pregnancy and had been treated with amoxicillin. Medications included prenatal vitamins and ferrous sulfate. The patient lived with her husband in New England and worked in health care. She had never smoked tobacco and did not drink alcohol or use illicit drugs. A brother had a history of childhood epilepsy, and her mother had macular degeneration.
Figure 1.

Funduscopic Images.
On examination, the visual acuity was 20/15 in the left eye, and there was no light perception in the right eye. The pupils were symmetric and reactive to light, although the response in the right pupil was sluggish; an afferent pupillary defect was present in the right eye. On the Ishihara color test, all plates were identified with the left eye. On a visual field test, there was a normal response in the left eye. The Ishihara color test and the visual field test could not be performed on the right eye because of poor vision. The results of a slit-lamp examination were normal, with no cells identified in the anterior chamber or vitreous. On a funduscopic examination (Figure 1A and 1B), the optic disk in the right eye was swollen and had temporal pallor; there was a small area of hypopigmentation close to the macula in the left eye. Optical coherence tomography revealed increased thickness of the retinal nerve fiber layer and circumferential thinning of the ganglion cell complex of the right eye; no abnormalities were noted in the left eye.
The blood creatinine level was 0.56 mg per deciliter (50 μmol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 μmol per liter]) and the blood alkaline phosphatase level 147 U per liter (reference range, 30 to 100). The results of other kidney-function and liver-function tests were normal, as were the blood levels of electrolytes, the complete blood count, and the results of coagulation tests. The blood C-reactive protein level was 15 mg per liter (reference value,  ) and the erythrocyte sedimentation rate 34 mm per hour (reference range, 0 to 20). A blood test for antinuclear antibodies was positive at a titer of 1:40 with a speckled pattern. Tests for antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) were negative. A diagnosis of atypical optic neuritis was considered. Because the patient was near delivery, further treatment was delayed until after the birth of her child, which occurred 3 days later.
Six days after delivery of the baby, the patient was admitted to this hospital, and additional studies were obtained. Lumbar puncture was performed. On cerebrospinal fluid (CSF) analysis, there were no nucleated cells, and the levels of protein, glucose, albumin, and IgG were normal. There was no oligoclonal banding after concentration of the CSF. Testing of the CSF was negative for syphilis antibodies and for antibodies against aquaporin-4.
Figure 2.

MRI of the Head.
Dr. Benjamin M. Kozak: MRI of the head (Figure 2), performed before and after the administration of intravenous contrast material, revealed prominent fusiform enlargement of a segment of the intraorbital right optic nerve with associated enhancement, as well as associated hyperintensity on the T2-weighted short-tau inversion recovery (STIR) sequence. There was no evidence of associated orbital edema or other orbital abnormalities. There was a punctate hyperintense focus within the left parietal subcortical white matter on the T2-weighted fluid-attenuated inversion recovery sequence, without associated enhancement or restricted diffusion.
Dr. Chwalisz: Treatment with intravenous methylprednisolone and daily plasmapheresis was administered. On the fourth hospital day, the soreness in the right eye had resolved, and there was light perception in the right eye. On the fifth hospital day, treatment with intravenous methylprednisolone was changed to oral prednisone. On the ninth hospital day, rituximab was administered, and the patient was discharged home with a prescription for a 7-week tapering course of prednisone.
During the next 3 weeks, treatment with rituximab was administered weekly. Two weeks after the last rituximab infusion, the patient was evaluated in the neuro-ophthalmology clinic at the hospital affiliated with this hospital. She reported no eye pain and only occasional headache, but she noted that the vision in the right eye had worsened. Examination revealed no light perception in the right eye, with an afferent pupillary defect. The results of a visual field test and the Ishihara color test were unchanged from the previous evaluation in the neuro-ophthalmology clinic. On a funduscopic examination (Figure 1C), the optic disk in the right eye was swollen and had more pronounced temporal pallor; optociliary shunt vessels were also newly present. Additional imaging studies were obtained.
Dr. Kozak: Follow-up MRI of the head (Figure 2) revealed no radiologically significant change in the segmental enlargement of the intraorbital right optic nerve, with persistent enhancement as well as hyperintensity on the T2-weighted STIR sequence. No new orbital abnormalities were present. In addition, the punctate lesion in the left parietal subcortical white matter was unchanged.
Dr. Chwalisz: A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with monocular vision loss, headache, and a swollen optic disk in the right eye. The MRI shows enlargement of the intraorbital right optic nerve. The patient was initially treated for optic neuritis, but her vision did not improve. The presence of optociliary shunt vessels, which are collateral blood vessels on the optic disk, are a classic sign of optic nerve sheath meningioma (ONSM). ONSM is a benign tumor that arises from the meninges of the optic nerve sheath and can cause progressive, painless, monocular vision loss. The MRI findings of fusiform enlargement of the optic nerve with enhancement are also consistent with ONSM.\n\nDiagnosis: Optic nerve sheath meningioma (ONSM)""
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}",Optic nerve sheath meningioma (ONSM),Y,"{
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        ""content"": ""The patient is a 30-year-old woman presenting with monocular vision loss in the right eye, headache, and soreness in the right eye. The differential diagnosis for this patient includes optic neuritis, ischemic optic neuropathy, compressive optic neuropathy, and infiltrative optic neuropathy. Optic neuritis is often associated with multiple sclerosis and can present with pain and vision loss, but it is usually self-limiting and improves with time, which is not the case in this patient. Ischemic optic neuropathy often presents suddenly and is associated with risk factors such as hypertension and diabetes, which this patient does not have. Compressive optic neuropathy could be caused by a mass or lesion compressing the optic nerve, but the MRI did not reveal any such abnormalities. Infiltrative optic neuropathy could be caused by an inflammatory or infectious process. Given the patient's history of Lyme disease, this could be a possibility, but the patient was treated for this and her symptoms did not improve. The patient's MRI showed enlargement of the intraorbital right optic nerve, which is consistent with an inflammatory process. The patient's vision loss did not improve with treatment for optic neuritis, suggesting that this is not the correct diagnosis. The patient's positive ANA test suggests an autoimmune process, and the lack of improvement with steroids suggests a more aggressive or atypical form of optic neuritis. The presence of optociliary shunt vessels is a classic sign of optic nerve sheath meningioma, but this is usually a slow-growing tumor and would not typically cause such rapid vision loss. Given the patient's symptoms, imaging findings, and lack of response to treatment, the most likely diagnosis is Neuromyelitis Optica Spectrum Disorder (NMOSD), a rare autoimmune disorder that affects the optic nerves and spinal cord. However, the patient's negative test for aquaporin-4 antibodies makes this less likely, as these are typically present in NMOSD. The patient's symptoms and imaging findings are also consistent with a diagnosis of chronic relapsing inflammatory optic neuropathy (CRION), a rare form of recurrent optic neuritis that is steroid-responsive but relapses on steroid withdrawal.\n\nDiagnosis: Chronic Relapsing Inflammatory Optic Neuropathy (CRION)""
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}",Chronic Relapsing Inflammatory Optic Neuropathy (CRION),N
10.1056/NEJMcpc2211354,"Case 35-2022: A 60-Year-Old Man with Progressive Dyspnea, Neck Swelling, and a Lung Mass","Hemoglobin (g/dl)	13.0–17.5	11.8	 	12.3
Hematocrit (%)	39.0–53.0	35.5	 	36.6
White-cell count (per μl)	400 ,000	10,500	 	11,560
Platelet count (per μl)	 	342,000	 	353,000
Sodium (mmol/liter)	137–146	129	 	132
Potassium (mmol/liter)	3.6–5.2	4.5	 	3.9
Chloride (mmol/liter)	98–110	94	 	98
Carbon dioxide (mmol/liter)	21–32	29	 	24
Urea nitrogen (mg/dl)	8–23	12	 	4
Creatinine (mg/dl)	0.55–1.30	0.51	 	0.61
Calcium (mg/dl)	 	9.3	 	8.3
Albumin (g/dl)	3.2–5.0	2.5	 	—
C-reactive protein (mg/dl)	0–0.80	18.10	—	—",Poorly differentiated adenocarcinoma of the lung complicated by superior vena cava syndrome.,Poorly differentiated adenocarcinoma of the lung complicated by superior vena cava syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 60-year-old man was transferred to this hospital for evaluation of new dyspnea, cough, neck swelling, and a lung mass.
Three days before the current admission, the patient was transported to another hospital by ambulance. He had a 5-day history of sore throat, swelling of his neck and both arms, and orthopnea. He reported that he had had progressive dyspnea with walking or lifting items at his job for the past year; the dyspnea had been most prominent during the 4 months before this evaluation and had been accompanied by persistent nonproductive cough. His daughter, a health care worker, called emergency medical services when she noticed that he had facial redness and flushing and learned of the swelling of his neck and arms.
Table 1.

Laboratory Data.
On evaluation at the other hospital, the temperature was 35.6°C, the heart rate 78 beats per minute, the blood pressure 121/57 mm Hg, the respiratory rate 19 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The face was flushed, and the neck was swollen. Breath sounds were absent in the right lung fields. The blood levels of troponin I and amylase were normal, as were the results of liver-function tests; other laboratory test results are shown in Table 1.
Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, reportedly revealed a new mass in the hilar region of the right upper lobe that measured 9.2 cm in greatest dimension. There was evidence of mass effect on the right main pulmonary artery and right main-stem and right upper-lobe bronchi, encasement of the right bronchus intermedius, occlusion of the superior vena cava (SVC) and narrowing of the right superior pulmonary vein, pulmonary emboli in the pulmonary artery of the left lower lobe, consolidation and atelectasis in the right upper lobe, chest-wall edema and extensive venous collateral vessels, and bilateral moderate-sized pleural effusions. The patient was admitted to the other hospital, and intravenous piperacillin–tazobactam and heparin were administered.
The next day, thoracentesis was performed, and 500 ml of cloudy yellow fluid was removed. On analysis of the pleural fluid, the fluid glucose level was 98 mg per deciliter (5.4 mmol per liter), the protein level 3.4 g per deciliter, the lactate dehydrogenase level 74 U per liter, and the pH 7.5. Gram’s staining of the pleural fluid revealed no organisms, and no malignant cells were identified on cytologic analysis. Ultrasonography of the legs showed no evidence of deep-vein thrombosis. CT of the head, performed without the administration of intravenous contrast material, reportedly showed no hemorrhage or stroke, and CT of the abdomen and pelvis reportedly revealed subcentimeter lucent areas in the iliac bones. The next day, the patient was transferred to the oncology unit of this hospital for further evaluation and care.
On admission to this hospital, the patient reported that, during the past 3 days, he had had progressive swelling of both upper arms, as well as pain in the right shoulder and arm. He noted weight loss of approximately 10 kg in the past 6 months, anorexia, hoarse voice, dizziness with changes in position (including bending forward), and dyspnea on exertion. A review of systems was negative for hemoptysis, chest pain, palpitations, nausea, changes in bowel habits, vomiting, abdominal pain, night sweats, headache, and diplopia.
Medical history included surgery on the shoulder and leg. The patient took no medications, and there were no known adverse reactions to medications. He was self-employed and had worked in plumbing and engineering. He had smoked two packs of cigarettes per day for 40 years and smoked marijuana occasionally. He drank five beers per day two times per week. His family history was notable for pancreatic cancer in his mother.
The temperature was 37.1°C, the heart rate 110 beats per minute, the blood pressure 114/66 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. The weight was 90 kg, the height 172 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 30.6. There was neck swelling and erythema, with no stridor. Jugular venous distention was present. On auscultation, the heart sounds were tachycardic but distant, and the lung sounds were markedly decreased on the right side. There was edema of the arms, with more pronounced swelling in the right arm than in the left arm, as well as erythema on the chest and evidence of engorged veins in the chest wall.
The blood level of glucose was normal, as were the results of liver-function tests; other laboratory test results are shown in Table 1. Electrocardiography revealed sinus tachycardia with premature atrial beats, borderline-low precordial lead voltage, and nonspecific ST-segment and T-wave changes.
Figure 1.

CT of the Chest.
Dr. Subba R. Digumarthy: Chest CT, performed after the administration of intravenous contrast material, revealed a persistent large central mass in the right upper lobe with occlusion of the right upper-lobe bronchus and collapse of the right upper lobe. There were multiple enlarged right mediastinal and right hilar lymph nodes (Figure 1A). The brachiocephalic veins and the SVC showed no opacification, and the presence of extensive collateral veins in the right chest wall was consistent with venous occlusion and SVC syndrome (Figure 1B and 1C). An incidental cyst was noted in the upper pole of the left kidney. There was no evidence of pericardial effusion. There was no other evidence of cancer in the abdomen. The diagnostic possibilities included non–small-cell lung cancer (NSCLC), small-cell lung cancer, metastasis from extrathoracic cancer, and lymphoma. Granulomatous infection and fibrosing mediastinitis were less likely in this case, given the imaging findings.
Angiography performed the next day confirmed that there was no opacification of the subclavian and brachiocephalic veins or the SVC and that extensive collateral veins were present in the arms. After removal of some of the clots, multiple overlapping stents were placed in the internal jugular veins, the brachiocephalic veins, and the SVC (Figure 1D and 1E and Video 1, available with the full text of this article at NEJM.org).
Figure 2.

Photograph Obtained during Bronchoscopy.
Dr. Colleen M. Keyes: On the fourth hospital day, rigid bronchoscopy revealed diffusely friable mucosa and dynamic airway narrowing of the right main-stem bronchus. Much of the airway narrowing appeared to be due to extrinsic compression (Figure 2). Balloon dilation of the airway was performed but did not result in resolution of the airway narrowing; therefore, an endobronchial stent was not placed. Endobronchial ultrasonography revealed a 1.5-cm mass near the carina, and transbronchial needle aspiration was subsequently performed.
Figure 3.

Specimens from Fine-Needle Aspiration.
Dr. Daniel Shepherd: During fine-needle aspiration of the subcarinal mass, a rapid on-site evaluation of the specimen was performed. Hematoxylin and eosin staining (Figure 3A and 3B) showed clusters of large epithelioid cells with anisonucleosis, irregularly contoured nuclei, prominent nucleoli, and occasional binucleated forms. There was a moderate amount of thin, delicate eosinophilic cytoplasm with occasional intracytoplasmic mucin. These findings are consistent with poorly differentiated adenocarcinoma. No morphologic features of small-cell carcinoma were seen, and immunohistochemical staining for neuroendocrine markers and for programmed death ligand 1 (PD-L1) was negative.
Dr. Dudzinski: Radiation and medical oncology management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 60-year-old man was transferred to this hospital for evaluation of new dyspnea, cough, neck swelling, and a lung mass.
Three days before the current admission, the patient was transported to another hospital by ambulance. He had a 5-day history of sore throat, swelling of his neck and both arms, and orthopnea. He reported that he had had progressive dyspnea with walking or lifting items at his job for the past year; the dyspnea had been most prominent during the 4 months before this evaluation and had been accompanied by persistent nonproductive cough. His daughter, a health care worker, called emergency medical services when she noticed that he had facial redness and flushing and learned of the swelling of his neck and arms.
Table 1.

Laboratory Data.
On evaluation at the other hospital, the temperature was 35.6°C, the heart rate 78 beats per minute, the blood pressure 121/57 mm Hg, the respiratory rate 19 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The face was flushed, and the neck was swollen. Breath sounds were absent in the right lung fields. The blood levels of troponin I and amylase were normal, as were the results of liver-function tests; other laboratory test results are shown in Table 1.
Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, reportedly revealed a new mass in the hilar region of the right upper lobe that measured 9.2 cm in greatest dimension. There was evidence of mass effect on the right main pulmonary artery and right main-stem and right upper-lobe bronchi, encasement of the right bronchus intermedius, occlusion of the superior vena cava (SVC) and narrowing of the right superior pulmonary vein, pulmonary emboli in the pulmonary artery of the left lower lobe, consolidation and atelectasis in the right upper lobe, chest-wall edema and extensive venous collateral vessels, and bilateral moderate-sized pleural effusions. The patient was admitted to the other hospital, and intravenous piperacillin–tazobactam and heparin were administered.
The next day, thoracentesis was performed, and 500 ml of cloudy yellow fluid was removed. On analysis of the pleural fluid, the fluid glucose level was 98 mg per deciliter (5.4 mmol per liter), the protein level 3.4 g per deciliter, the lactate dehydrogenase level 74 U per liter, and the pH 7.5. Gram’s staining of the pleural fluid revealed no organisms, and no malignant cells were identified on cytologic analysis. Ultrasonography of the legs showed no evidence of deep-vein thrombosis. CT of the head, performed without the administration of intravenous contrast material, reportedly showed no hemorrhage or stroke, and CT of the abdomen and pelvis reportedly revealed subcentimeter lucent areas in the iliac bones. The next day, the patient was transferred to the oncology unit of this hospital for further evaluation and care.
On admission to this hospital, the patient reported that, during the past 3 days, he had had progressive swelling of both upper arms, as well as pain in the right shoulder and arm. He noted weight loss of approximately 10 kg in the past 6 months, anorexia, hoarse voice, dizziness with changes in position (including bending forward), and dyspnea on exertion. A review of systems was negative for hemoptysis, chest pain, palpitations, nausea, changes in bowel habits, vomiting, abdominal pain, night sweats, headache, and diplopia.
Medical history included surgery on the shoulder and leg. The patient took no medications, and there were no known adverse reactions to medications. He was self-employed and had worked in plumbing and engineering. He had smoked two packs of cigarettes per day for 40 years and smoked marijuana occasionally. He drank five beers per day two times per week. His family history was notable for pancreatic cancer in his mother.
The temperature was 37.1°C, the heart rate 110 beats per minute, the blood pressure 114/66 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. The weight was 90 kg, the height 172 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 30.6. There was neck swelling and erythema, with no stridor. Jugular venous distention was present. On auscultation, the heart sounds were tachycardic but distant, and the lung sounds were markedly decreased on the right side. There was edema of the arms, with more pronounced swelling in the right arm than in the left arm, as well as erythema on the chest and evidence of engorged veins in the chest wall.
The blood level of glucose was normal, as were the results of liver-function tests; other laboratory test results are shown in Table 1. Electrocardiography revealed sinus tachycardia with premature atrial beats, borderline-low precordial lead voltage, and nonspecific ST-segment and T-wave changes.
Figure 1.

CT of the Chest.
Dr. Subba R. Digumarthy: Chest CT, performed after the administration of intravenous contrast material, revealed a persistent large central mass in the right upper lobe with occlusion of the right upper-lobe bronchus and collapse of the right upper lobe. There were multiple enlarged right mediastinal and right hilar lymph nodes (Figure 1A). The brachiocephalic veins and the SVC showed no opacification, and the presence of extensive collateral veins in the right chest wall was consistent with venous occlusion and SVC syndrome (Figure 1B and 1C). An incidental cyst was noted in the upper pole of the left kidney. There was no evidence of pericardial effusion. There was no other evidence of cancer in the abdomen. The diagnostic possibilities included non–small-cell lung cancer (NSCLC), small-cell lung cancer, metastasis from extrathoracic cancer, and lymphoma. Granulomatous infection and fibrosing mediastinitis were less likely in this case, given the imaging findings.
Angiography performed the next day confirmed that there was no opacification of the subclavian and brachiocephalic veins or the SVC and that extensive collateral veins were present in the arms. After removal of some of the clots, multiple overlapping stents were placed in the internal jugular veins, the brachiocephalic veins, and the SVC (Figure 1D and 1E and Video 1, available with the full text of this article at NEJM.org).
Figure 2.

Photograph Obtained during Bronchoscopy.
Dr. Colleen M. Keyes: On the fourth hospital day, rigid bronchoscopy revealed diffusely friable mucosa and dynamic airway narrowing of the right main-stem bronchus. Much of the airway narrowing appeared to be due to extrinsic compression (Figure 2). Balloon dilation of the airway was performed but did not result in resolution of the airway narrowing; therefore, an endobronchial stent was not placed. Endobronchial ultrasonography revealed a 1.5-cm mass near the carina, and transbronchial needle aspiration was subsequently performed.
Figure 3.

Specimens from Fine-Needle Aspiration.
Dr. Daniel Shepherd: During fine-needle aspiration of the subcarinal mass, a rapid on-site evaluation of the specimen was performed. Hematoxylin and eosin staining (Figure 3A and 3B) showed clusters of large epithelioid cells with anisonucleosis, irregularly contoured nuclei, prominent nucleoli, and occasional binucleated forms. There was a moderate amount of thin, delicate eosinophilic cytoplasm with occasional intracytoplasmic mucin. These findings are consistent with poorly differentiated adenocarcinoma. No morphologic features of small-cell carcinoma were seen, and immunohistochemical staining for neuroendocrine markers and for programmed death ligand 1 (PD-L1) was negative.
Dr. Dudzinski: Radiation and medical oncology management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of dyspnea, cough, neck swelling, and a lung mass, along with his history of heavy smoking, suggest a lung-related issue. The CT scan revealed a mass in the right upper lobe of the lung, with occlusion of the right upper-lobe bronchus and collapse of the right upper lobe. There were also multiple enlarged right mediastinal and right hilar lymph nodes. These findings suggest a malignancy. The fine-needle aspiration of the subcarinal mass confirmed the presence of poorly differentiated adenocarcinoma. Therefore, the final diagnosis is lung adenocarcinoma.""
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        ""content"": ""The patient is a 60-year-old man with a history of heavy smoking who presents with new dyspnea, cough, neck swelling, and a lung mass. He also reports weight loss, anorexia, hoarse voice, and dizziness. His symptoms and history suggest a malignancy, likely lung cancer. The differential diagnosis includes non-small cell lung cancer (NSCLC), small cell lung cancer, metastasis from extrathoracic cancer, and lymphoma. Granulomatous infection and fibrosing mediastinitis are less likely given the imaging findings. The CT scan reveals a large central mass in the right upper lobe with occlusion of the right upper-lobe bronchus and collapse of the right upper lobe. There are also multiple enlarged right mediastinal and right hilar lymph nodes. The patient also has superior vena cava (SVC) syndrome, which is often caused by malignancies such as lung cancer or lymphoma. The patient's symptoms, history, and imaging findings are most consistent with lung cancer. The fine-needle aspiration of the subcarinal mass shows clusters of large epithelioid cells with anisonucleosis, irregularly contoured nuclei, prominent nucleoli, and occasional binucleated forms, which are consistent with poorly differentiated adenocarcinoma. This, along with the patient's heavy smoking history, makes NSCLC the most likely diagnosis.\n\nDiagnosis: Non-small cell lung cancer (NSCLC)""
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10.1056/NEJMcpc2115857,Case 34-2022: A 57-Year-Old Woman with Covid-19 and Delusions,,"Cotard‚Äö√Ñ√¥s syndrome, catatonia, depression, and seizure after coronavirus disease 2019.","Cotard’s syndrome, catatonia, and depression after coronavirus disease 2019.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 57-year-old woman with major depressive disorder and coronavirus disease 2019 (Covid-19) was evaluated at a hospital affiliated with this hospital because she was having delusions that she was dead.
The patient had been in her usual state of health until 2 weeks before this presentation, when myalgias, cough, sore throat, nausea, and vomiting developed. She sought evaluation at the primary care clinic of an academic medical center affiliated with this hospital (the two hospitals are part of the same health care system). Nucleic acid testing of a nasopharyngeal swab was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, and the patient was instructed to quarantine at home. She lived with her father and assisted him with activities of daily living; he also received a diagnosis of Covid-19.
During the following week, the patient’s cough persisted, and new shortness of breath developed. Her symptoms worsened; she felt that she was unable to take care of her father. Emergency medical services were called, and the patient and her father were taken to the emergency department of the other hospital, where they were both admitted for worsening Covid-19 pneumonia. The patient was treated with supplemental oxygen, remdesivir, and dexamethasone. Treatment with remdesivir was stopped on hospital day 4 when the blood aminotransferase levels increased to three times the upper limit of the normal range.
During the hospitalization, the patient was noted to have intermittent anxiety, particularly when discharge planning for her father was discussed. She and her brother declined to have their father discharged to a rehabilitation center and instead planned for him to eventually return home to quarantine with the patient. On hospital day 6, the patient’s oxygen saturation was normal while she was breathing ambient air, and the blood aminotransferase levels had improved. She was discharged home with instructions to quarantine and continue taking dexamethasone.
One day after discharge, the patient’s brother spoke to her on the telephone. He thought that she seemed to be confused and unable to take care of herself, and he asked her to return to the emergency department of the other hospital.
On evaluation in the emergency department, the patient explained that she was unsure why her brother had asked her to return to the hospital, and she said that she wanted to go home. She also expressed that she felt anxious about being home alone after discharge and overwhelmed about needing to care for her father at home once he was discharged from the hospital. The myalgias, cough, and shortness of breath had abated; she had no fevers, visual or auditory hallucinations, or suicidal or homicidal ideation.
The patient had a history of major depressive disorder, which had been diagnosed during the second decade of life. At the time of diagnosis, she had been admitted to a psychiatric hospital and had received electroconvulsive therapy; thereafter, she had been discharged to a partial hospital program. She had been hospitalized for psychiatric symptoms twice since then, once for major depressive disorder and once for a mixed bipolar episode that was due to insomnia and anxious distress. The latter episode was associated with catatonic features and was treated with electroconvulsive therapy.
The patient had no history of suicidal or homicidal ideation or attempts and no history of violence. She had hypertension, diabetes, obesity, and gastroesophageal reflux disease. Medications included dexamethasone, bupropion, fluoxetine, olanzapine, losartan, metformin, and pantoprazole. Sulfa drugs had caused angioedema, and lisinopril had caused cough. The patient was born in the Caribbean and had emigrated four decades earlier, first to southwestern Europe and then to the United States 2 years later. She lived in an apartment in an urban area of New England with her father, who had mild dementia. She did not drink alcohol, smoke cigarettes, or use illicit substances.
On examination, the temperature was 37.2°C, the pulse 97 beats per minute, the blood pressure 153/95 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 93% while the patient was breathing ambient air. The patient was alert and oriented but guarded, with a flat affect. She appeared to be more anxious than she had been during the previous hospitalization. She paced around the room and perseverated about the care of her father. The remainder of the examination was normal.
The blood levels of electrolytes and glucose were normal, as were the results of liver-function and kidney-function tests. The white-cell count was 11,490 per microliter (reference range, 4000 to 11,000), with neutrophil predominance; the complete blood count with differential count was otherwise normal. Urinalysis and a radiograph of the chest were normal. Treatment with dexamethasone was stopped, and the patient was admitted to the hospital to facilitate discharge to a rehabilitation center for continued care.
On hospital day 3, the patient was noted to be more withdrawn, and she began responding to questions with one-word answers or silence. When she was encouraged to speak more, she continued to perseverate about the care of her father. When she was asked to elaborate on her concerns, she stated, “He is dead. I am dead.”
The patient appeared disheveled, sullen, and anxious. She laid in bed motionless with her eyes open and looking forward, and she responded briefly to questions in a quiet voice with slowed speech. Her thoughts were perseverative and tangential. There was no evidence that she had loosening of associations, hallucinations, or suicidal or homicidal ideation. She had poor insight and judgment. Memory, attention, concentration, abstract reasoning, and fund of knowledge were normal. When her arms and legs were lifted against gravity and released, they fell to the bed without resistance; with encouragement, she was able to move them. Muscle tone was normal, with no rigidity or waxy flexibility. Imaging studies were obtained.
Figure 1.

CT of the Head.
Dr. Aaron B. Paul: Computed tomography (CT) of the head (Figure 1), performed without the administration of intravenous contrast material, revealed no evidence of an acute territorial infarct, intracranial mass, or hemorrhage. There was nonspecific moderate confluent hypoattenuation involving the supratentorial white matter.
Dr. Kritzer: Clonazepam was administered, and the dose of olanzapine was increased. Admission to an inpatient psychiatric unit was recommended. During the next week, while awaiting placement in an inpatient psychiatric unit, the patient continued to show signs of anxiety and a depressed mood. She said, “I am dead. I do not exist. I am not real.” She also believed that her father and brother, as well as her nurses and doctors, were dead. The patient was selectively mute and motionless, but she talked and moved with encouragement. She expressed that she felt directly responsible for the Covid-19 pandemic and asked to be thrown out of the window. She had the sensation that her bladder was gone and that she could not urinate, although she had been observed urinating independently. She felt that she could not eat, although she had been observed eating breakfast daily. On hospital day 9, the patient was transferred to the inpatient psychiatric unit of the other hospital.
A diagnosis and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 57-year-old woman with major depressive disorder and coronavirus disease 2019 (Covid-19) was evaluated at a hospital affiliated with this hospital because she was having delusions that she was dead.
The patient had been in her usual state of health until 2 weeks before this presentation, when myalgias, cough, sore throat, nausea, and vomiting developed. She sought evaluation at the primary care clinic of an academic medical center affiliated with this hospital (the two hospitals are part of the same health care system). Nucleic acid testing of a nasopharyngeal swab was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, and the patient was instructed to quarantine at home. She lived with her father and assisted him with activities of daily living; he also received a diagnosis of Covid-19.
During the following week, the patient’s cough persisted, and new shortness of breath developed. Her symptoms worsened; she felt that she was unable to take care of her father. Emergency medical services were called, and the patient and her father were taken to the emergency department of the other hospital, where they were both admitted for worsening Covid-19 pneumonia. The patient was treated with supplemental oxygen, remdesivir, and dexamethasone. Treatment with remdesivir was stopped on hospital day 4 when the blood aminotransferase levels increased to three times the upper limit of the normal range.
During the hospitalization, the patient was noted to have intermittent anxiety, particularly when discharge planning for her father was discussed. She and her brother declined to have their father discharged to a rehabilitation center and instead planned for him to eventually return home to quarantine with the patient. On hospital day 6, the patient’s oxygen saturation was normal while she was breathing ambient air, and the blood aminotransferase levels had improved. She was discharged home with instructions to quarantine and continue taking dexamethasone.
One day after discharge, the patient’s brother spoke to her on the telephone. He thought that she seemed to be confused and unable to take care of herself, and he asked her to return to the emergency department of the other hospital.
On evaluation in the emergency department, the patient explained that she was unsure why her brother had asked her to return to the hospital, and she said that she wanted to go home. She also expressed that she felt anxious about being home alone after discharge and overwhelmed about needing to care for her father at home once he was discharged from the hospital. The myalgias, cough, and shortness of breath had abated; she had no fevers, visual or auditory hallucinations, or suicidal or homicidal ideation.
The patient had a history of major depressive disorder, which had been diagnosed during the second decade of life. At the time of diagnosis, she had been admitted to a psychiatric hospital and had received electroconvulsive therapy; thereafter, she had been discharged to a partial hospital program. She had been hospitalized for psychiatric symptoms twice since then, once for major depressive disorder and once for a mixed bipolar episode that was due to insomnia and anxious distress. The latter episode was associated with catatonic features and was treated with electroconvulsive therapy.
The patient had no history of suicidal or homicidal ideation or attempts and no history of violence. She had hypertension, diabetes, obesity, and gastroesophageal reflux disease. Medications included dexamethasone, bupropion, fluoxetine, olanzapine, losartan, metformin, and pantoprazole. Sulfa drugs had caused angioedema, and lisinopril had caused cough. The patient was born in the Caribbean and had emigrated four decades earlier, first to southwestern Europe and then to the United States 2 years later. She lived in an apartment in an urban area of New England with her father, who had mild dementia. She did not drink alcohol, smoke cigarettes, or use illicit substances.
On examination, the temperature was 37.2°C, the pulse 97 beats per minute, the blood pressure 153/95 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 93% while the patient was breathing ambient air. The patient was alert and oriented but guarded, with a flat affect. She appeared to be more anxious than she had been during the previous hospitalization. She paced around the room and perseverated about the care of her father. The remainder of the examination was normal.
The blood levels of electrolytes and glucose were normal, as were the results of liver-function and kidney-function tests. The white-cell count was 11,490 per microliter (reference range, 4000 to 11,000), with neutrophil predominance; the complete blood count with differential count was otherwise normal. Urinalysis and a radiograph of the chest were normal. Treatment with dexamethasone was stopped, and the patient was admitted to the hospital to facilitate discharge to a rehabilitation center for continued care.
On hospital day 3, the patient was noted to be more withdrawn, and she began responding to questions with one-word answers or silence. When she was encouraged to speak more, she continued to perseverate about the care of her father. When she was asked to elaborate on her concerns, she stated, “He is dead. I am dead.”
The patient appeared disheveled, sullen, and anxious. She laid in bed motionless with her eyes open and looking forward, and she responded briefly to questions in a quiet voice with slowed speech. Her thoughts were perseverative and tangential. There was no evidence that she had loosening of associations, hallucinations, or suicidal or homicidal ideation. She had poor insight and judgment. Memory, attention, concentration, abstract reasoning, and fund of knowledge were normal. When her arms and legs were lifted against gravity and released, they fell to the bed without resistance; with encouragement, she was able to move them. Muscle tone was normal, with no rigidity or waxy flexibility. Imaging studies were obtained.
Figure 1.

CT of the Head.
Dr. Aaron B. Paul: Computed tomography (CT) of the head (Figure 1), performed without the administration of intravenous contrast material, revealed no evidence of an acute territorial infarct, intracranial mass, or hemorrhage. There was nonspecific moderate confluent hypoattenuation involving the supratentorial white matter.
Dr. Kritzer: Clonazepam was administered, and the dose of olanzapine was increased. Admission to an inpatient psychiatric unit was recommended. During the next week, while awaiting placement in an inpatient psychiatric unit, the patient continued to show signs of anxiety and a depressed mood. She said, “I am dead. I do not exist. I am not real.” She also believed that her father and brother, as well as her nurses and doctors, were dead. The patient was selectively mute and motionless, but she talked and moved with encouragement. She expressed that she felt directly responsible for the Covid-19 pandemic and asked to be thrown out of the window. She had the sensation that her bladder was gone and that she could not urinate, although she had been observed urinating independently. She felt that she could not eat, although she had been observed eating breakfast daily. On hospital day 9, the patient was transferred to the inpatient psychiatric unit of the other hospital.
A diagnosis and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Cotard's Syndrome. The patient's belief that she is dead, along with her belief that others around her are also dead, are characteristic of Cotard's Syndrome. This condition is a rare mental disorder in which the affected person holds the delusional belief that they are already dead, do not exist, or have lost their blood or internal organs. The patient's history of major depressive disorder and recent stressors (COVID-19 diagnosis and responsibility for her father's care) could have contributed to the onset of this syndrome.""
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        ""content"": ""Cotard's Syndrome. The patient's delusions of being dead, not existing, and not being real, along with her belief that others around her are also dead, are characteristic of Cotard's Syndrome. This condition is a rare mental disorder in which the affected person holds the delusional belief that they are already dead, do not exist, or have lost their blood or internal organs. It is often associated with severe depression and psychosis, both of which the patient has a history of. The patient's selective muteness and motionlessness, as well as her feelings of being directly responsible for the Covid-19 pandemic, further support this diagnosis.""
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        ""content"": ""Cotard's Syndrome. \n\nThis patient presents with a history of major depressive disorder and recent COVID-19 infection. She has delusions of being dead and believes that others around her are also dead. She also has feelings of non-existence and being directly responsible for the COVID-19 pandemic. These symptoms are consistent with Cotard's Syndrome, a rare condition where the affected person holds the delusional belief that they are already dead, do not exist, or have lost their blood or internal organs. This condition is often associated with severe depression and psychosis. The patient's history of major depressive disorder and recent stressful events (COVID-19 infection and the responsibility of caring for her father) could have triggered this episode. The patient's CT scan did not reveal any acute changes that could explain her symptoms, further supporting a psychiatric diagnosis.""
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10.1056/NEJMcpc2201235,Case 33-2022: An 11-Year-Old Girl with Redness of the Eyes,"Hemoglobin (g/dl)	11.3–13.4	—	10.2
Hematocrit (%)	32.3–38.3	34.0	31.3
Platelet count (per μl)	187,00 76,000	175,000	233,000
White-cell count (per μl)	5410–9700	5600	4690
Differential count (per μl)			
Neutrophils	2580–5950	—	2960
Lymphocytes	123 760	—	900
Monocytes	19 10	—	610
Eosinophils	40–190	—	160
Basophils	10–50	—	20
Creatinine (mg/dl)*	0.30–1.00	—	0.75
Alanine aminotransferase (U/liter)	3–30	28	17
Aspartate aminotransferase (U/liter)	2–40	34	31
Alkaline phosphatase (U/liter)	6 35	—	129
Albumin (g/dl)	3.0–4.6	—	4.2
Total protein (g/dl)	5.5–8.2	—	8.8
C-reactive protein (mg/liter)	 	2.8	3.6
Erythrocyte sedimentation rate (mm/hr)	 0	—	90
Angiotensin-converting enzyme (U/liter)	24–121	74	—
Lysozyme (μg/ml)	 .75	2.60	3.83
Antinuclear antibody	Negative	Negative	Negative
Antineutrophil cytoplasmic antibody	Negative	Negative	Negative",Sarcoidosis.,Sarcoidosis or tuberculosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 11-year-old girl was evaluated in the rheumatology clinic of this hospital because of redness of the eyes.
The patient had been well until 8 weeks before the current evaluation, when she noticed mild eye redness, which was worse in the right eye than in the left eye. There was intermittent swelling of the eyelids but no photophobia, itching, pain, tearing, or discharge. The patient’s parents administered naphazoline hydrochloride and glycerin eye drops, but the eye redness did not abate. When the eye redness had persisted for 2 weeks, the patient was taken to the pediatrics clinic of another hospital. She was given a 7-day course of an oral antibiotic agent as empirical treatment for possible preseptal cellulitis.
Five weeks before the current evaluation, the eye redness persisted despite treatment, and the patient was referred to the ophthalmology clinic of the other hospital. The blood pressure was not measured during this evaluation. The visual acuity with correction was 20/20 in the right eye and 20/25 in the left eye. The pupils were symmetric and reactive to light, with no relative afferent pupillary defect. Slit-lamp examination revealed abundant white cells in the anterior chamber of both eyes, with a greater amount in the right eye than in the left eye. There were also keratic precipitates, posterior synechiae, and rare iris nodules in the right eye. Funduscopic examination was notable for optic-disk swelling and peripheral retinal hemorrhages in both eyes, as well as perivascular exudates in the right eye. Cyclopentolate eye drops in the right eye and prednisolone eye drops in both eyes were prescribed.
Table 1.

Laboratory Data.
During the subsequent 3 weeks, additional tests were performed in the pediatrics clinic of the other hospital. Screening blood tests for human immunodeficiency virus (HIV) types 1 and 2, syphilis, and Lyme disease were negative. An interferon-γ release assay for Mycobacterium tuberculosis was indeterminate. Other laboratory test results are shown in Table 1. Radiography of the chest revealed hilar fullness.
Figure 1.

Initial Imaging Studies.
Dr. Maria G. Figueiro Longo: Computed tomography (CT) of the chest and abdomen (Figure 1A and 1B), performed after the administration of intravenous contrast material, showed a normal-appearing thymus. However, diffuse lymphadenopathy was detected in the mediastinum, upper abdomen, and axillae, with the largest lymph node measuring 2.0 cm by 1.3 cm by 1.8 cm.
Dr. Diacovo: Two weeks before the current evaluation, the patient was asked to present to the emergency department of the other hospital for an expedited workup. On evaluation, she described eye redness that had persisted but decreased in severity. She reported no fever, weight loss, night sweats, rash, headache, cough, shortness of breath, or joint pain. On examination, the temperature was 37.0°C, the blood pressure 96/61 mm Hg, the heart rate 95 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 18.3.
Figure 2.

Fundus Photographs.
The patient appeared well, with no oral lesions or rash. The visual acuity was unchanged. Slit-lamp examination revealed keratic precipitates and white cells in the anterior chamber of both eyes, with a greater amount in the right eye than in the left eye. There were extensive posterior synechiae in the right eye. Funduscopic examination (Figure 2) showed vitreous white cells, optic-disk swelling, perivascular exudates, peripheral retinal hemorrhages, and cotton-wool spots in both eyes. The lungs were clear on auscultation. Urinalysis was normal. Other laboratory test results are shown in Table 1. Methylprednisolone was administered, and the patient was admitted to the other hospital.
During the next 4 days, additional tests were performed, and sputum specimens were obtained for an acid-fast bacilli smear and culture. Optical coherence tomography revealed optic-disk swelling but no cystoid macular swelling. Fluorescein angiography revealed optic-disk leakage with areas of peripheral retinal nonperfusion and some vessel leakage.
Dr. Figueiro Longo: Magnetic resonance imaging (MRI) of the head (Figure 1C), performed before and after the administration of intravenous contrast material, showed protrusion and enhancement of the optic disks and enhancement of the irises, a finding consistent with the clinical diagnosis of uveitis. There was no evidence of optic neuritis or perineuritis.
Dr. Diacovo: The administration of cyclopentolate eye drops in the right eye and prednisolone eye drops in both eyes was continued. Treatment with oral prednisone was started, and a regimen of rifampin, isoniazid, ethambutol, and pyrazinamide was begun as empirical treatment for possible tuberculosis. On the fifth hospital day, the patient was discharged home. She was instructed to follow up in the ophthalmology clinic of the other hospital and was referred to the rheumatology clinic of this hospital.
In the rheumatology clinic, additional history was obtained. The patient had had normal growth and development and was currently in middle school. She had received all routine childhood vaccinations. She had emigrated from West Africa to the United States 6 years earlier; since then, she had lived with her mother and father in a suburban town in New England and had not traveled outside the region. Six months before this evaluation, an interferon-γ release assay for M. tuberculosis had been positive. At that time, the patient had received a prescription for a medication to treat latent tuberculosis infection; however, the patient’s parents could not recall giving the medication to the patient. She was taking the prescribed cyclopentolate and prednisolone eye drops, oral prednisone, and regimen of rifampin, isoniazid, ethambutol, and pyrazinamide. There were no known drug allergies. The patient’s parents were healthy.
A diagnosis and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 11-year-old girl was evaluated in the rheumatology clinic of this hospital because of redness of the eyes.
The patient had been well until 8 weeks before the current evaluation, when she noticed mild eye redness, which was worse in the right eye than in the left eye. There was intermittent swelling of the eyelids but no photophobia, itching, pain, tearing, or discharge. The patient’s parents administered naphazoline hydrochloride and glycerin eye drops, but the eye redness did not abate. When the eye redness had persisted for 2 weeks, the patient was taken to the pediatrics clinic of another hospital. She was given a 7-day course of an oral antibiotic agent as empirical treatment for possible preseptal cellulitis.
Five weeks before the current evaluation, the eye redness persisted despite treatment, and the patient was referred to the ophthalmology clinic of the other hospital. The blood pressure was not measured during this evaluation. The visual acuity with correction was 20/20 in the right eye and 20/25 in the left eye. The pupils were symmetric and reactive to light, with no relative afferent pupillary defect. Slit-lamp examination revealed abundant white cells in the anterior chamber of both eyes, with a greater amount in the right eye than in the left eye. There were also keratic precipitates, posterior synechiae, and rare iris nodules in the right eye. Funduscopic examination was notable for optic-disk swelling and peripheral retinal hemorrhages in both eyes, as well as perivascular exudates in the right eye. Cyclopentolate eye drops in the right eye and prednisolone eye drops in both eyes were prescribed.
Table 1.

Laboratory Data.
During the subsequent 3 weeks, additional tests were performed in the pediatrics clinic of the other hospital. Screening blood tests for human immunodeficiency virus (HIV) types 1 and 2, syphilis, and Lyme disease were negative. An interferon-γ release assay for Mycobacterium tuberculosis was indeterminate. Other laboratory test results are shown in Table 1. Radiography of the chest revealed hilar fullness.
Figure 1.

Initial Imaging Studies.
Dr. Maria G. Figueiro Longo: Computed tomography (CT) of the chest and abdomen (Figure 1A and 1B), performed after the administration of intravenous contrast material, showed a normal-appearing thymus. However, diffuse lymphadenopathy was detected in the mediastinum, upper abdomen, and axillae, with the largest lymph node measuring 2.0 cm by 1.3 cm by 1.8 cm.
Dr. Diacovo: Two weeks before the current evaluation, the patient was asked to present to the emergency department of the other hospital for an expedited workup. On evaluation, she described eye redness that had persisted but decreased in severity. She reported no fever, weight loss, night sweats, rash, headache, cough, shortness of breath, or joint pain. On examination, the temperature was 37.0°C, the blood pressure 96/61 mm Hg, the heart rate 95 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 18.3.
Figure 2.

Fundus Photographs.
The patient appeared well, with no oral lesions or rash. The visual acuity was unchanged. Slit-lamp examination revealed keratic precipitates and white cells in the anterior chamber of both eyes, with a greater amount in the right eye than in the left eye. There were extensive posterior synechiae in the right eye. Funduscopic examination (Figure 2) showed vitreous white cells, optic-disk swelling, perivascular exudates, peripheral retinal hemorrhages, and cotton-wool spots in both eyes. The lungs were clear on auscultation. Urinalysis was normal. Other laboratory test results are shown in Table 1. Methylprednisolone was administered, and the patient was admitted to the other hospital.
During the next 4 days, additional tests were performed, and sputum specimens were obtained for an acid-fast bacilli smear and culture. Optical coherence tomography revealed optic-disk swelling but no cystoid macular swelling. Fluorescein angiography revealed optic-disk leakage with areas of peripheral retinal nonperfusion and some vessel leakage.
Dr. Figueiro Longo: Magnetic resonance imaging (MRI) of the head (Figure 1C), performed before and after the administration of intravenous contrast material, showed protrusion and enhancement of the optic disks and enhancement of the irises, a finding consistent with the clinical diagnosis of uveitis. There was no evidence of optic neuritis or perineuritis.
Dr. Diacovo: The administration of cyclopentolate eye drops in the right eye and prednisolone eye drops in both eyes was continued. Treatment with oral prednisone was started, and a regimen of rifampin, isoniazid, ethambutol, and pyrazinamide was begun as empirical treatment for possible tuberculosis. On the fifth hospital day, the patient was discharged home. She was instructed to follow up in the ophthalmology clinic of the other hospital and was referred to the rheumatology clinic of this hospital.
In the rheumatology clinic, additional history was obtained. The patient had had normal growth and development and was currently in middle school. She had received all routine childhood vaccinations. She had emigrated from West Africa to the United States 6 years earlier; since then, she had lived with her mother and father in a suburban town in New England and had not traveled outside the region. Six months before this evaluation, an interferon-γ release assay for M. tuberculosis had been positive. At that time, the patient had received a prescription for a medication to treat latent tuberculosis infection; however, the patient’s parents could not recall giving the medication to the patient. She was taking the prescribed cyclopentolate and prednisolone eye drops, oral prednisone, and regimen of rifampin, isoniazid, ethambutol, and pyrazinamide. There were no known drug allergies. The patient’s parents were healthy.
A diagnosis and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Tuberculosis-associated uveitis. The patient's symptoms of persistent eye redness, swelling of the eyelids, and white cells in the anterior chamber of both eyes are indicative of uveitis. The patient's history of a positive interferon-\u0152\u2265 release assay for M. tuberculosis, along with the presence of mediastinal and abdominal lymphadenopathy on CT scan, suggest a diagnosis of tuberculosis. The patient's uveitis could therefore be associated with her tuberculosis infection.""
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        ""content"": ""Sarcoidosis. The patient's symptoms of persistent eye redness, swelling of the eyelids, and white cells in the anterior chamber of both eyes are indicative of uveitis, an inflammation of the uvea, the middle layer of the eye. The presence of keratic precipitates, posterior synechiae, and iris nodules further support this diagnosis. The patient's chest radiograph revealed hilar fullness, and a CT scan showed diffuse lymphadenopathy in the mediastinum, upper abdomen, and axillae, which are common findings in sarcoidosis. The patient's negative screenings for HIV, syphilis, and Lyme disease, as well as the indeterminate result for a tuberculosis assay, suggest that an infectious cause is unlikely. The patient's age and the absence of joint pain make juvenile idiopathic arthritis, another common cause of uveitis in children, less likely. Therefore, the most likely diagnosis is sarcoidosis, a systemic inflammatory disease that often affects the lungs and lymph nodes and can also cause uveitis.""
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        ""content"": ""This is an 11-year-old girl who presents with persistent redness of the eyes, swelling of the eyelids, and white cells in the anterior chamber of both eyes. These findings suggest an inflammatory process. The differential diagnosis for this patient includes uveitis, preseptal cellulitis, and systemic diseases that can present with eye involvement such as juvenile idiopathic arthritis, sarcoidosis, and tuberculosis. The patient was initially treated for preseptal cellulitis, but her symptoms persisted despite treatment, making this diagnosis less likely. The patient does not have joint pain, which is a common symptom in juvenile idiopathic arthritis, making this diagnosis less likely. The patient has hilar fullness on chest radiography and diffuse lymphadenopathy on CT, which are findings suggestive of sarcoidosis or tuberculosis. However, the patient had a positive interferon-\u03b3 release assay for M. tuberculosis six months prior to this evaluation, which suggests latent tuberculosis infection. Given the patient's persistent eye symptoms, systemic findings, and history of latent tuberculosis infection, the most likely diagnosis is tuberculosis uveitis.\n\nDiagnosis: Tuberculosis Uveitis.""
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}",Tuberculosis Uveitis,Y
10.1056/NEJMcpc2201245,Case 32-2022: A 76-Year-Old Man with Postoperative Cardiogenic Shock and Diffuse Rash,"Hemoglobin (g/dl)	 	14.3	12.2	10.7	10.1	—	8.4
Hematocrit (%)	 	43.2	37.1	32.2	30.0	—	26.5
White-cell count (per μl)	 	6280	4700	11,730	9970	—	10,340
Differential count (per μl)							
Neutrophils	1100–7700	3860	2860	—	6540	—	6670
Lymphocytes	 	1090	650	—	520	—	620
Monocytes	 	810	550	—	910	—	500
Eosinophils	 	400	590	—	1720	—	2450
Platelet count (per μl)	 	170,000	105,000	116,000	133,000	—	163,000
Sodium (mmol/liter)	 	143	139	144	144	—	145
Potassium (mmol/liter)	 	3.1	3.2	4.1	4.3	—	4.7
Chloride (mmol/liter)	 	99	99	109	111	—	114
Carbon dioxide (mmol/liter)	 	29	25	20	21	—	22
Urea nitrogen (mg/dl)	 	38	27	25	44	—	42
Creatinine (mg/dl)	 	2.00	1.33	1.55	2.26	—	2.51
Glucose (mg/dl)	 	104	90	190	119	—	105
Lactate (mmol/liter)	 	1.3	1.7	6.4	1.7	—	1.5
Alanine aminotransferase (U/liter)	 	15	16	22	<5	—	<5
Aspartate aminotransferase (U/liter)	 	24	22	206	25	—	23
High-sensitivity troponin T (ng/liter)	0–9	51	—	—	—	—	—
N-terminal pro–B-type natriuretic peptide (pg/ml)	<900	11,084	—	—	—	—	—
Thyrotropin (μIU/ml)	0.4–5.00	16.60	—	—	—	—	—
Free thyroxine (ng/dl)	0.9–1.8	1.1	—	—	—	—	—
Mixed venous oxygen saturation (%)	65.0–75.0	—	—	68.3	41.3	—	51.4
Central venous pressure (mm Hg)	 	—	—	8	3	7	7
Diastolic pulmonary arterial pressure (mm Hg)	9–16	—	—	19	11	5	13
Systemic vascular resistance (dyn/sec/cm−5)	800–1200	—	—	746	1160	1048	—",Eosinophilic myocarditis and drug reaction with eosinophilia and systemic symptoms (DRESS).,Drug reaction with eosinophilia and systemic symptoms complicated by eosinophilic myocarditis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old man was evaluated in the intensive care unit of this hospital for persistent postoperative cardiogenic shock and new diffuse rash after undergoing mitral-valve replacement.
Two months before this evaluation, the patient was admitted to another hospital with anorexia, generalized weakness, fatigue, and edema. Examination of the lungs was notable for decreased breath sounds and basilar crackles. The level of N-terminal pro–B-type natriuretic peptide was 15,895 pg per milliliter (reference value, <1500).
Figure 1.

Cardiac and Radiographic Studies.
Dr. Matthew T. Stib: A chest radiograph (Figure 1A) showed a mildly enlarged cardiac silhouette, as well as evidence of pulmonary edema and bilateral pleural effusions.
Dr. Dudzinski: At the other hospital, intravenous furosemide was administered. Blood cultures obtained at the time of admission grew methicillin-sensitive Staphylococcus aureus (MSSA) in four of four bottles. Transesophageal echocardiography (TEE) reportedly revealed moderate-to-severe mitral regurgitation and a 7-mm vegetation on the anterior leaflet of the mitral valve. Treatment with intravenous oxacillin was initiated; a 4-week course of treatment was planned, after which the patient was scheduled for follow-up in the cardiac surgery clinic at this hospital.
However, 3 weeks after discharge, the patient reported dyspnea on exertion, fatigue, progressive edema of the legs, and weight gain of 7 kg. He was admitted to this hospital for further evaluation and treatment.
Medical history was notable for hypertension, right bundle-branch block, hypothyroidism, and prostatism, as well as atrial fibrillation, for which the patient had undergone cardioversion. Surgical history included tooth extraction for a painful dental abscess 6 weeks before admission to the other hospital, appendectomy, arthroplasty of the left hip after a fall 3 years earlier, and repair of a meniscus tear in the left knee. Medications included oxacillin administered intravenously every 4 hours and oral furosemide, sotalol, rivaroxaban, levothyroxine, and tamsulosin. He had had no known adverse drug reactions.
The patient was retired and lived with his spouse. He reported that, before his admission to the other hospital, he had been riding a bicycle a few miles several times per week. He had previously smoked cigarettes but had quit 30 years earlier; he consumed one beer weekly and used no other substances. His family history was notable for atrial fibrillation.
The temperature was 36.7°C, the heart rate 83 beats per minute, the blood pressure 120/72 mm Hg, and the oxygen saturation 96% while the patient was breathing ambient air. He appeared fatigued. The jugular venous pressure was elevated, at 15 cm of water. The cardiac impulse was discrete and was not displaced. Auscultation of the chest revealed an irregularly irregular cardiac rhythm, with a grade 3/6 holosystolic murmur at the left sternal border and apex that did not change with respiration, and bibasilar crackles. There was 2+ pitting edema in the legs. A peripherally inserted central catheter was present in the right arm.
Table 1.

Laboratory and Hemodynamic Data.
The blood levels of calcium, magnesium, albumin, lipase, glycated hemoglobin, alkaline phosphatase, and bilirubin were normal, and a screening test for human immunodeficiency virus antigen and antibodies was negative. Other laboratory test results are shown in Table 1. Cultures of blood were obtained. An electrocardiogram (Figure 1B) showed atrial fibrillation, multifocal ventricular premature beats, and right bundle-branch block.
Dr. Stib: A chest radiograph (Figure 1C) showed bilateral pulmonary edema, which was more prominent in the right lung than in the left lung, as well as pleural effusions and left atrial enlargement. The tip of a peripherally inserted central catheter was appropriately positioned in the lower superior vena cava.
Dr. Dudzinski: Treatment with intravenous oxacillin and furosemide was continued. TEE (Figure 1D) and transthoracic echocardiography (TTE) revealed a normal-sized left ventricle with an ejection fraction of 61%, dilatation of the right ventricle with normal function, dilatation of both atria, mitral-valve perforation and thickening, severe mitral regurgitation due to mitral-valve perforation, and moderate tricuspid regurgitation with a right ventricular systolic pressure of 48 mm Hg (also see Videos 1 and 2, available with the full text of this article at NEJM.org). Coronary angiography revealed 70% stenosis in the proximal left anterior descending coronary artery and 90% stenosis in the middle right coronary artery.
On hospital day 11, cardiac surgery was performed. The patient underwent bioprosthetic mitral-valve replacement, along with two-vessel coronary-artery bypass grafting and amputation of the left atrial appendage. TEE performed after the surgical procedure revealed a well-seated mitral prosthesis with trace central regurgitation, as well as mild biventricular systolic dysfunction. Subsequently, on transfer to the intensive care unit, the blood pressure was 108/52 mm Hg and the cardiac index 3.0 liters per minute per square meter of body-surface area while the patient was receiving epinephrine (at a rate of 2 μg per minute), norepinephrine (10 μg per minute), and vasopressin (0.04 U per minute). An electrocardiogram (Figure 1E) showed atrial fibrillation, right bundle-branch block, and ventricular premature beats. During postoperative day 1, the patient had increased ventricular ectopy and a 25-beat run of ventricular tachycardia. Laboratory and hemodynamic data are shown in Table 1.
Dr. Stib: An anteroposterior chest radiograph (Figure 1F) showed left atrial enlargement, bilateral pulmonary edema, and basilar atelectasis, along with sternotomy wires, an endotracheal tube, a catheter in the right main pulmonary artery, bilateral chest tubes, and a mediastinal drain.
Dr. Dudzinski: Treatment with intravenous amiodarone was started, and the epinephrine infusion was discontinued.
On postoperative day 2, the trachea was extubated, and mechanical ventilation was discontinued. The cardiac index had decreased to less than 2.0 liters per minute per square meter, and intravenous milrinone was initiated. The next day, a 35-beat run of ventricular tachycardia occurred. On postoperative day 4, given that the cardiac index was less than 1.9 liters per minute per square meter, intravenous dopamine was started. On postoperative day 5, deep-vein thrombosis was identified in the right lower leg, and treatment with warfarin was started. A truncal macular rash was noted. TTE revealed a left ventricular ejection fraction of 32%, right ventricular dysfunction, atrial dilatation, trace central prosthetic mitral regurgitation with a mean transmitral gradient of 5 mm Hg measured at 70 beats per minute, and moderate-to-severe tricuspid regurgitation (see Video 3). There was also worsening renal function. Milrinone was stopped and epinephrine initiated.
On postoperative day 8, microbiologic cultures obtained during the surgical procedure showed no growth; the patient’s oxacillin treatment was switched to cefazolin. During the next few days, the rash became more confluent and extended to the face, back, arms, and neck in addition to the trunk, but there was no mucosal involvement. Examination of the joints was normal, and there was no lymphadenopathy or hepatosplenomegaly. The arms and legs were cool, and urine output had decreased, despite continued therapy with intravenous epinephrine, norepinephrine, and dopamine. Laboratory test results are shown in Table 1. Repeat TTE on postoperative day 13 revealed borderline left ventricular dilatation with an ejection fraction of 37%, right ventricular dilatation and dysfunction, and moderate-to-severe tricuspid regurgitation.
Additional diagnostic tests were performed, and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old man was evaluated in the intensive care unit of this hospital for persistent postoperative cardiogenic shock and new diffuse rash after undergoing mitral-valve replacement.
Two months before this evaluation, the patient was admitted to another hospital with anorexia, generalized weakness, fatigue, and edema. Examination of the lungs was notable for decreased breath sounds and basilar crackles. The level of N-terminal pro–B-type natriuretic peptide was 15,895 pg per milliliter (reference value, <1500).
Figure 1.

Cardiac and Radiographic Studies.
Dr. Matthew T. Stib: A chest radiograph (Figure 1A) showed a mildly enlarged cardiac silhouette, as well as evidence of pulmonary edema and bilateral pleural effusions.
Dr. Dudzinski: At the other hospital, intravenous furosemide was administered. Blood cultures obtained at the time of admission grew methicillin-sensitive Staphylococcus aureus (MSSA) in four of four bottles. Transesophageal echocardiography (TEE) reportedly revealed moderate-to-severe mitral regurgitation and a 7-mm vegetation on the anterior leaflet of the mitral valve. Treatment with intravenous oxacillin was initiated; a 4-week course of treatment was planned, after which the patient was scheduled for follow-up in the cardiac surgery clinic at this hospital.
However, 3 weeks after discharge, the patient reported dyspnea on exertion, fatigue, progressive edema of the legs, and weight gain of 7 kg. He was admitted to this hospital for further evaluation and treatment.
Medical history was notable for hypertension, right bundle-branch block, hypothyroidism, and prostatism, as well as atrial fibrillation, for which the patient had undergone cardioversion. Surgical history included tooth extraction for a painful dental abscess 6 weeks before admission to the other hospital, appendectomy, arthroplasty of the left hip after a fall 3 years earlier, and repair of a meniscus tear in the left knee. Medications included oxacillin administered intravenously every 4 hours and oral furosemide, sotalol, rivaroxaban, levothyroxine, and tamsulosin. He had had no known adverse drug reactions.
The patient was retired and lived with his spouse. He reported that, before his admission to the other hospital, he had been riding a bicycle a few miles several times per week. He had previously smoked cigarettes but had quit 30 years earlier; he consumed one beer weekly and used no other substances. His family history was notable for atrial fibrillation.
The temperature was 36.7°C, the heart rate 83 beats per minute, the blood pressure 120/72 mm Hg, and the oxygen saturation 96% while the patient was breathing ambient air. He appeared fatigued. The jugular venous pressure was elevated, at 15 cm of water. The cardiac impulse was discrete and was not displaced. Auscultation of the chest revealed an irregularly irregular cardiac rhythm, with a grade 3/6 holosystolic murmur at the left sternal border and apex that did not change with respiration, and bibasilar crackles. There was 2+ pitting edema in the legs. A peripherally inserted central catheter was present in the right arm.
Table 1.

Laboratory and Hemodynamic Data.
The blood levels of calcium, magnesium, albumin, lipase, glycated hemoglobin, alkaline phosphatase, and bilirubin were normal, and a screening test for human immunodeficiency virus antigen and antibodies was negative. Other laboratory test results are shown in Table 1. Cultures of blood were obtained. An electrocardiogram (Figure 1B) showed atrial fibrillation, multifocal ventricular premature beats, and right bundle-branch block.
Dr. Stib: A chest radiograph (Figure 1C) showed bilateral pulmonary edema, which was more prominent in the right lung than in the left lung, as well as pleural effusions and left atrial enlargement. The tip of a peripherally inserted central catheter was appropriately positioned in the lower superior vena cava.
Dr. Dudzinski: Treatment with intravenous oxacillin and furosemide was continued. TEE (Figure 1D) and transthoracic echocardiography (TTE) revealed a normal-sized left ventricle with an ejection fraction of 61%, dilatation of the right ventricle with normal function, dilatation of both atria, mitral-valve perforation and thickening, severe mitral regurgitation due to mitral-valve perforation, and moderate tricuspid regurgitation with a right ventricular systolic pressure of 48 mm Hg (also see Videos 1 and 2, available with the full text of this article at NEJM.org). Coronary angiography revealed 70% stenosis in the proximal left anterior descending coronary artery and 90% stenosis in the middle right coronary artery.
On hospital day 11, cardiac surgery was performed. The patient underwent bioprosthetic mitral-valve replacement, along with two-vessel coronary-artery bypass grafting and amputation of the left atrial appendage. TEE performed after the surgical procedure revealed a well-seated mitral prosthesis with trace central regurgitation, as well as mild biventricular systolic dysfunction. Subsequently, on transfer to the intensive care unit, the blood pressure was 108/52 mm Hg and the cardiac index 3.0 liters per minute per square meter of body-surface area while the patient was receiving epinephrine (at a rate of 2 μg per minute), norepinephrine (10 μg per minute), and vasopressin (0.04 U per minute). An electrocardiogram (Figure 1E) showed atrial fibrillation, right bundle-branch block, and ventricular premature beats. During postoperative day 1, the patient had increased ventricular ectopy and a 25-beat run of ventricular tachycardia. Laboratory and hemodynamic data are shown in Table 1.
Dr. Stib: An anteroposterior chest radiograph (Figure 1F) showed left atrial enlargement, bilateral pulmonary edema, and basilar atelectasis, along with sternotomy wires, an endotracheal tube, a catheter in the right main pulmonary artery, bilateral chest tubes, and a mediastinal drain.
Dr. Dudzinski: Treatment with intravenous amiodarone was started, and the epinephrine infusion was discontinued.
On postoperative day 2, the trachea was extubated, and mechanical ventilation was discontinued. The cardiac index had decreased to less than 2.0 liters per minute per square meter, and intravenous milrinone was initiated. The next day, a 35-beat run of ventricular tachycardia occurred. On postoperative day 4, given that the cardiac index was less than 1.9 liters per minute per square meter, intravenous dopamine was started. On postoperative day 5, deep-vein thrombosis was identified in the right lower leg, and treatment with warfarin was started. A truncal macular rash was noted. TTE revealed a left ventricular ejection fraction of 32%, right ventricular dysfunction, atrial dilatation, trace central prosthetic mitral regurgitation with a mean transmitral gradient of 5 mm Hg measured at 70 beats per minute, and moderate-to-severe tricuspid regurgitation (see Video 3). There was also worsening renal function. Milrinone was stopped and epinephrine initiated.
On postoperative day 8, microbiologic cultures obtained during the surgical procedure showed no growth; the patient’s oxacillin treatment was switched to cefazolin. During the next few days, the rash became more confluent and extended to the face, back, arms, and neck in addition to the trunk, but there was no mucosal involvement. Examination of the joints was normal, and there was no lymphadenopathy or hepatosplenomegaly. The arms and legs were cool, and urine output had decreased, despite continued therapy with intravenous epinephrine, norepinephrine, and dopamine. Laboratory test results are shown in Table 1. Repeat TTE on postoperative day 13 revealed borderline left ventricular dilatation with an ejection fraction of 37%, right ventricular dilatation and dysfunction, and moderate-to-severe tricuspid regurgitation.
Additional diagnostic tests were performed, and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Dressler syndrome. The patient's symptoms of fatigue, anorexia, and generalized weakness, along with the presence of a new rash, are consistent with Dressler syndrome, a form of pericarditis that can occur after heart surgery. The patient's elevated jugular venous pressure and the presence of crackles in the lungs suggest fluid overload, which can occur in Dressler syndrome due to inflammation of the pericardium. The patient's history of recent heart surgery is a major risk factor for Dressler syndrome. The patient's symptoms did not improve with antibiotics, suggesting that the cause is not infectious. The patient's rash, which is not a common symptom of heart failure or bacterial endocarditis, is another clue pointing towards Dressler syndrome.""
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        ""content"": ""This is a 76-year-old man with a history of hypertension, right bundle-branch block, hypothyroidism, and prostatism, as well as atrial fibrillation, who presented with persistent postoperative cardiogenic shock and new diffuse rash after undergoing mitral-valve replacement. The patient's history of MSSA infection and recent surgery suggest the possibility of a postoperative infection or sepsis. However, the absence of fever and negative blood cultures argue against this. The patient's rash could be a drug reaction, but the absence of mucosal involvement and the fact that the rash appeared while the patient was on antibiotics he had previously tolerated well make this less likely. The patient's cardiac issues could be due to his underlying heart disease, but his persistent shock despite aggressive treatment raises the possibility of a mechanical issue related to his recent surgery. The patient's worsening renal function could be due to his low cardiac output, but it could also suggest a systemic process such as vasculitis. Given the patient's age, history of atrial fibrillation, and recent surgery, a thromboembolic event is also a possibility. The differential diagnosis includes sepsis, drug reaction, mechanical complication of surgery, vasculitis, and thromboembolism.\n\nDiagnosis:\nThe most likely diagnosis is cardiogenic shock due to mechanical complication of mitral valve replacement surgery.""
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10.1056/NEJMcpc2201239,"Case 31-2022: A 72-Year-Old Man with Heartburn, Nausea, and Inability to Eat","Sodium (mmol/liter)	13 6	138
Potassium (mmol/liter)	 	3.4
Chloride (mmol/liter)	 	93
Carbon dioxide (mmol/liter)	 	33
Urea nitrogen (mg/dl)	 	27
Creatinine (mg/dl)	 	0.93
Glucose (mg/dl)	 	110
Calcium (mg/dl)	 	9.6
Magnesium (mg/dl)	 	2.1
Phosphorus (mg/dl)	 	3.3
Prealbumin (mg/dl)	2 	22
Albumin (g/dl)	 	3.8
Globulin (g/dl)	 	3.6
Total protein (g/dl)	6. .3	7.4
Direct bilirubin (mg/dl)	0. 	0.2
Total bilirubin (mg/dl)	0.0–1.0	0.5
Alanine aminotransferase (U/liter)	 	25
Aspartate aminotransferase (U/liter)	 	19
Alkaline phosphatase (U/liter)	 	86
Glycated hemoglobin (%)	4.3–5.6	6.7
Hemoglobin (g/dl)	13.5–17.4	14.4
Hematocrit (%)	 	42.8
Platelet count (per μl)	 	197,000
White-cell count (per μl)	 	7890",Linitis plastica (invasive gastric adenocarcinoma).,Linitis plastica (invasive gastric adenocarcinoma).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 72-year-old man was transferred to this hospital because of heartburn, nausea, and the inability to eat solid and liquid food.
The patient had a history of gastroesophageal reflux disease. The symptoms had been well controlled with the use of daily omeprazole therapy until 11 months before this admission, when heartburn recurred despite treatment. At that time, the patient also noticed nausea after eating and early satiation. During the next 9 months, the heartburn and nausea slowly increased in severity. To help manage his symptoms, the patient adjusted his diet from solid food to soft solid food.
Two months before this admission, the patient sought evaluation at the gastroenterology clinic of another hospital. The glycated hemoglobin level was 6.1% (reference range, 4.3 to 5.6). Esophagogastroduodenoscopy (EGD) was performed. Although the patient had not eaten food for 24 hours before the procedure, the stomach could not be adequately visualized because there was a large amount of residual food; no intraluminal masses were seen.
A scintigraphy study of gastric emptying was performed. During the study, 88% of the gastric contents were retained at 1 hour, 88% at 2 hours, 81% at 3 hours, and 80% at 4 hours. In a patient with normal gastric emptying, less than 60% of the gastric contents would be retained at 2 hours and less than 10% at 4 hours. Thus, the results were consistent with severely delayed gastric emptying. The patient was told that he had idiopathic gastroparesis and underwent trials of several medications. Ondansetron caused constipation, erythromycin caused burning while swallowing and abdominal cramping, and metoclopramide and scopolamine did not lead to a decrease in the patient’s symptoms.
During the 2 months after the evaluation in the gastroenterology clinic, the patient adjusted his diet from soft solid food to blended solid food. Two weeks before this admission, he adjusted his diet to primarily liquid food, such as nutritional supplement drinks, protein shakes, and ice cream. When the patient was no longer able to drink liquids, he sought evaluation at the emergency department of the other hospital.
On evaluation, the patient described epigastric burning and nausea after eating. He had lost 13.6 kg of weight in the preceding year, including 5.4 kg in the past 2 weeks. He had no recent history of illness, night sweats, vomiting, dysphagia, odynophagia, abdominal pain, or diarrhea.
Figure 1.

CT Scan of the Abdomen.
Dr. David A. Rosman: Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed a patulous esophagus, along with wall thickening in scattered areas of the upper and lower segments of the esophagus. There was abnormal circumferential wall thickening (≤13 mm) in the stomach, particularly at the antrum, incisura, and pyloric canal (Figure 1). The antrum was decompressed or nonexpansile, and the rest of the stomach was distended. There were multiple bilateral pulmonary nodules (≤5 mm in diameter) and multiple hepatic hypodensities (  mm in diameter), as well as a pancreatic cyst (5 mm in diameter) and an exophytic renal lesion (8 mm in diameter).
Dr. Badran: A nasogastric tube was inserted. Treatment with intravenous pantoprazole was started, and intravenous lorazepam was administered for nausea. The patient was admitted to the other hospital.
During the subsequent week, the patient received vitamin and mineral supplements for severe malnutrition. He remained unable to drink liquids. On the 7th hospital day, a peripherally inserted central catheter was placed, and total parenteral nutrition was administered. The patient was monitored for refeeding syndrome. On the 15th hospital day, he was transferred to this hospital for further treatment.
On transfer to this hospital, additional history was obtained. The patient had a history of prediabetes, hypertension, dyslipidemia, diverticulosis, glaucoma, and basal cell carcinoma of the ear that had been resected. Five years before this admission, EGD had revealed a widely patent Schatzki’s ring, an irregular-appearing Z line, and a few gastric polyps; examination of an esophageal biopsy specimen had revealed no abnormalities. Colonoscopy had shown two tubular adenomas. The patient had undergone orthognathic surgery, but there was no history of abdominal surgery. Medications included omeprazole, lisinopril, atorvastatin, vitamin D supplements, and bimatoprost and bromonidine eye drops. Sulfa drugs had caused a rash.
The patient lived with his wife in a rural area of New England. He had previously served in the military and currently worked as a biotechnologist. He had never smoked tobacco, and he drank alcohol rarely. His mother and paternal aunt had died of colon cancer, his father of lung cancer, his maternal grandmother of breast cancer, and his maternal grandfather of prostate cancer. His two children and two grandchildren were healthy.
Table 1.

Laboratory Data.
On examination, the temperature was 37.7°C, the blood pressure 128/76 mm Hg, the pulse 105 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. He was thin and had a nasogastric tube in place. He had normal mood, affect, and insight. The abdomen was flat, soft, and nondistended, with mild tenderness in the epigastrium on palpation. There was no palpable lymphadenopathy. Distal sensory and motor function were normal. Laboratory test results are shown in Table 1.
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 72-year-old man was transferred to this hospital because of heartburn, nausea, and the inability to eat solid and liquid food.
The patient had a history of gastroesophageal reflux disease. The symptoms had been well controlled with the use of daily omeprazole therapy until 11 months before this admission, when heartburn recurred despite treatment. At that time, the patient also noticed nausea after eating and early satiation. During the next 9 months, the heartburn and nausea slowly increased in severity. To help manage his symptoms, the patient adjusted his diet from solid food to soft solid food.
Two months before this admission, the patient sought evaluation at the gastroenterology clinic of another hospital. The glycated hemoglobin level was 6.1% (reference range, 4.3 to 5.6). Esophagogastroduodenoscopy (EGD) was performed. Although the patient had not eaten food for 24 hours before the procedure, the stomach could not be adequately visualized because there was a large amount of residual food; no intraluminal masses were seen.
A scintigraphy study of gastric emptying was performed. During the study, 88% of the gastric contents were retained at 1 hour, 88% at 2 hours, 81% at 3 hours, and 80% at 4 hours. In a patient with normal gastric emptying, less than 60% of the gastric contents would be retained at 2 hours and less than 10% at 4 hours. Thus, the results were consistent with severely delayed gastric emptying. The patient was told that he had idiopathic gastroparesis and underwent trials of several medications. Ondansetron caused constipation, erythromycin caused burning while swallowing and abdominal cramping, and metoclopramide and scopolamine did not lead to a decrease in the patient’s symptoms.
During the 2 months after the evaluation in the gastroenterology clinic, the patient adjusted his diet from soft solid food to blended solid food. Two weeks before this admission, he adjusted his diet to primarily liquid food, such as nutritional supplement drinks, protein shakes, and ice cream. When the patient was no longer able to drink liquids, he sought evaluation at the emergency department of the other hospital.
On evaluation, the patient described epigastric burning and nausea after eating. He had lost 13.6 kg of weight in the preceding year, including 5.4 kg in the past 2 weeks. He had no recent history of illness, night sweats, vomiting, dysphagia, odynophagia, abdominal pain, or diarrhea.
Figure 1.

CT Scan of the Abdomen.
Dr. David A. Rosman: Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed a patulous esophagus, along with wall thickening in scattered areas of the upper and lower segments of the esophagus. There was abnormal circumferential wall thickening (≤13 mm) in the stomach, particularly at the antrum, incisura, and pyloric canal (Figure 1). The antrum was decompressed or nonexpansile, and the rest of the stomach was distended. There were multiple bilateral pulmonary nodules (≤5 mm in diameter) and multiple hepatic hypodensities (  mm in diameter), as well as a pancreatic cyst (5 mm in diameter) and an exophytic renal lesion (8 mm in diameter).
Dr. Badran: A nasogastric tube was inserted. Treatment with intravenous pantoprazole was started, and intravenous lorazepam was administered for nausea. The patient was admitted to the other hospital.
During the subsequent week, the patient received vitamin and mineral supplements for severe malnutrition. He remained unable to drink liquids. On the 7th hospital day, a peripherally inserted central catheter was placed, and total parenteral nutrition was administered. The patient was monitored for refeeding syndrome. On the 15th hospital day, he was transferred to this hospital for further treatment.
On transfer to this hospital, additional history was obtained. The patient had a history of prediabetes, hypertension, dyslipidemia, diverticulosis, glaucoma, and basal cell carcinoma of the ear that had been resected. Five years before this admission, EGD had revealed a widely patent Schatzki’s ring, an irregular-appearing Z line, and a few gastric polyps; examination of an esophageal biopsy specimen had revealed no abnormalities. Colonoscopy had shown two tubular adenomas. The patient had undergone orthognathic surgery, but there was no history of abdominal surgery. Medications included omeprazole, lisinopril, atorvastatin, vitamin D supplements, and bimatoprost and bromonidine eye drops. Sulfa drugs had caused a rash.
The patient lived with his wife in a rural area of New England. He had previously served in the military and currently worked as a biotechnologist. He had never smoked tobacco, and he drank alcohol rarely. His mother and paternal aunt had died of colon cancer, his father of lung cancer, his maternal grandmother of breast cancer, and his maternal grandfather of prostate cancer. His two children and two grandchildren were healthy.
Table 1.

Laboratory Data.
On examination, the temperature was 37.7°C, the blood pressure 128/76 mm Hg, the pulse 105 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. He was thin and had a nasogastric tube in place. He had normal mood, affect, and insight. The abdomen was flat, soft, and nondistended, with mild tenderness in the epigastrium on palpation. There was no palpable lymphadenopathy. Distal sensory and motor function were normal. Laboratory test results are shown in Table 1.
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of gastroesophageal reflux disease and has been experiencing heartburn, nausea, and difficulty eating solid and liquid food. Despite treatment, his symptoms have worsened. A scintigraphy study of gastric emptying showed severely delayed gastric emptying, consistent with gastroparesis. However, the patient did not respond to treatment for gastroparesis. A CT scan revealed abnormal circumferential wall thickening in the stomach, particularly at the antrum, incisura, and pyloric canal. This, along with the patient's inability to eat or drink, suggests a more serious condition. Given the patient's age, history, and symptoms, a gastric malignancy is a likely diagnosis. \n\nDiagnosis: Gastric cancer.""
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        ""content"": ""The patient is a 72-year-old man with a history of gastroesophageal reflux disease who presents with heartburn, nausea, and the inability to eat solid and liquid food. He has lost significant weight over the past year and has been diagnosed with severely delayed gastric emptying. The differential diagnosis for this patient includes gastroparesis, gastric outlet obstruction, gastric cancer, and peptic ulcer disease. Gastroparesis is a possibility given the patient's symptoms and the results of the gastric emptying study. However, the patient's symptoms did not improve with medications typically used to treat gastroparesis. Gastric outlet obstruction could also cause the patient's symptoms, but the CT scan did not reveal any masses that could be causing an obstruction. Peptic ulcer disease could cause similar symptoms, but the patient's symptoms did not improve with pantoprazole, a medication used to treat peptic ulcers. The CT scan revealed abnormal circumferential wall thickening in the stomach, particularly at the antrum, incisura, and pyloric canal. This finding, along with the patient's symptoms and weight loss, is concerning for gastric cancer. The patient also has multiple bilateral pulmonary nodules and multiple hepatic hypodensities, which could be metastases from a primary gastric cancer.\n\nDiagnosis: Gastric cancer with possible metastases to the lungs and liver.""
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10.1056/NEJMcpc2201243,Case 30-2022: A Newborn Girl with Hypoglycemia,"Hemoglobin (g/dl)	14.5–22.5	17.2
Hematocrit (%)	45.0–67.0	51.2
Platelet count (per μl)	 	95,000
White-cell count (per μl)	940 4,000	8630
Reticulocytes (%)	2.1–4.8	7.0
Haptoglobin (mg/dl)	3 00	 
Sodium (mmol/liter)	 	142
Potassium (mmol/liter)	 	3.7
Chloride (mmol/liter)	98–106	109
Carbon dioxide (mmol/liter)	22–27	21
Urea nitrogen (mg/dl)	5–20	6
Creatinine (mg/dl)	0.30–1.00	0.77
Glucose (mg/dl)	 	60
Calcium (mg/dl)	 	9.3
Uric acid (mg/dl)	2.3–6.6	4.0
Lactate dehydrogenase (U/liter)	11 10	1173
Albumin (g/dl)	 	3.2
Globulin (g/dl)	 	1.1
Total protein (g/dl)	6. .3	4.3
Direct bilirubin (mg/dl)	0. 	2.2
Total bilirubin (mg/dl)	2. .0	20.4
Alanine aminotransferase (U/liter)	 	10
Aspartate aminotransferase (U/liter)	45–150	37
Alkaline phosphatase (U/liter)	83–248	216",Neonatal hypoglycemia due to biologically active teratoma and the Sotos syndrome.,Sacrococcygeal teratoma with neural and pancreatic elements.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A newborn girl was transferred to the neonatal intensive care unit (ICU) of this hospital because of hypoglycemia.
The patient’s mother was a 27-year-old woman (gravida 1, para 1) who had received prenatal care at another hospital. At 34 weeks of gestation, an ultrasonographic survey of the fetal anatomy had reportedly revealed an avascular intraabdominal cystic mass that was located near the bladder and measured 3.7 cm by 2.1 cm by 2.0 cm. A sacral dimple was noted. The patient’s mother was referred to the maternal–fetal medicine clinic of the other hospital; she declined follow-up imaging and amniocentesis.
At 37 weeks 6 days of gestation, premature labor occurred, and the patient’s mother was taken to a second hospital. A fetal heart tracing was noted to be nonreactive with minimal variability. The fetal biophysical profile score was 4 out of 8, indicating decreased breathing motion and body movement but normal tone and amniotic fluid volume. An emergency cesarean section was performed.
On delivery, the newborn had limp tone and poor respiratory effort. The birth weight was 2963 g (19th percentile), the length 48 cm (20th percentile), and the head circumference 35 cm (77th percentile). The Apgar scores at 1 minute and 5 minutes were 7 and 9, respectively. The patient was transferred to the newborn nursery.
In the nursery, the patient was noted to be jittery. Oxygen therapy was administered through a low-flow nasal cannula. The blood glucose level was reportedly less than 10 mg per deciliter (0.6 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]) and the bilirubin level 16.0 mg per deciliter (274 μmol per liter; reference range, 2.0 to 15.0 mg per deciliter [34 to 257 μmol per liter]). A chest radiograph showed a normal cardiac shadow and findings indicative of retained fetal lung fluid. The newborn was fed, and a bolus of dextrose was administered; however, a repeat blood glucose level was 2 mg per deciliter (0.1 mmol per liter). A continuous infusion of dextrose was started. Phototherapy and empirical treatment with ampicillin and gentamicin were administered.
During the next 3 days, the patient’s blood glucose level remained low, with a maximum level of 61 mg per deciliter (3.4 mmol per liter), even though the glucose infusion rate was increased and enteral feeding with formula was initiated. On the fourth day of life, she was transferred to the neonatal ICU of this hospital for further treatment.
On admission to the neonatal ICU, additional history was obtained. Before the ultrasonographic survey at 34 weeks of gestation, the pregnancy had been normal. The patient’s mother had taken prenatal vitamins. Prenatal maternal screening had been negative for gonorrhea, chlamydia, and syphilis, as well as human immunodeficiency virus, hepatitis B virus, and group B streptococcal infections; there was evidence of immunity to rubella virus. The maternal ABO blood type was AB, Rh positive. The newborn’s parents had immigrated to the United States from the Caribbean and now lived in a suburb in New England. The patient’s mother, father, and half brother were healthy.
On examination, the patient was alert and appeared comfortable. The temperature was 36.9°C, the heart rate 148 beats per minute, the blood pressure 79/45 mm Hg, the respiratory rate 49 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The anterior and posterior fontanelles were flat and soft. The lungs were clear on auscultation. The abdomen was soft without distention, tenderness, or palpable masses. Two sacral dimples with visible bases were noted. The female genitalia appeared normal, but the anus was displaced anteriorly.
Table 1.

Laboratory Data.
The blood glucose level was 60 mg per deciliter (3.3 mmol per liter) while the patient was receiving dextrose at a glucose infusion rate of 10.5 mg per kilogram of body weight per minute. The total bilirubin level was 20.4 mg per deciliter (349 μmol per liter). Other laboratory test results are shown in Table 1.
Figure 1.

Ultrasound Images of the Pelvis.
Figure 2.

MRI of the Pelvis.
Dr. Sjirk J. Westra: A chest radiograph showed clear lungs. Abdominal and pelvic ultrasonography (Figure 1) revealed a large solid–cystic mass anterior to the sacrum that measured 2.7 cm by 3.0 cm by 5.7 cm, with the rectum passing anteriorly to the mass. Results of spinal ultrasonography were normal, as were results of cranial ultrasonography performed through the anterior fontanelle. In addition, magnetic resonance imaging (MRI) of the abdomen, pelvis, and spine (Figure 2) showed a presacral solid–cystic mass that measured 2.7 cm by 2.8 cm by 5.9 cm, with a small extension into the ischiorectal fossa on the right side. There was no evidence of abdominal lymphadenopathy or involvement of the sacral spine.
Dr. Perez: During the next few days, the patient continued to receive dextrose at a high glucose infusion rate to maintain normoglycemia. At 5 days of life, a small bowel movement occurred. The blood lactate dehydrogenase level was 1173 U per liter (reference range, 110 to 210) and the beta human chorionic gonadotropin level 10.7 mIU per milliliter (reference range, <1.1).
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A newborn girl was transferred to the neonatal intensive care unit (ICU) of this hospital because of hypoglycemia.
The patient’s mother was a 27-year-old woman (gravida 1, para 1) who had received prenatal care at another hospital. At 34 weeks of gestation, an ultrasonographic survey of the fetal anatomy had reportedly revealed an avascular intraabdominal cystic mass that was located near the bladder and measured 3.7 cm by 2.1 cm by 2.0 cm. A sacral dimple was noted. The patient’s mother was referred to the maternal–fetal medicine clinic of the other hospital; she declined follow-up imaging and amniocentesis.
At 37 weeks 6 days of gestation, premature labor occurred, and the patient’s mother was taken to a second hospital. A fetal heart tracing was noted to be nonreactive with minimal variability. The fetal biophysical profile score was 4 out of 8, indicating decreased breathing motion and body movement but normal tone and amniotic fluid volume. An emergency cesarean section was performed.
On delivery, the newborn had limp tone and poor respiratory effort. The birth weight was 2963 g (19th percentile), the length 48 cm (20th percentile), and the head circumference 35 cm (77th percentile). The Apgar scores at 1 minute and 5 minutes were 7 and 9, respectively. The patient was transferred to the newborn nursery.
In the nursery, the patient was noted to be jittery. Oxygen therapy was administered through a low-flow nasal cannula. The blood glucose level was reportedly less than 10 mg per deciliter (0.6 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]) and the bilirubin level 16.0 mg per deciliter (274 μmol per liter; reference range, 2.0 to 15.0 mg per deciliter [34 to 257 μmol per liter]). A chest radiograph showed a normal cardiac shadow and findings indicative of retained fetal lung fluid. The newborn was fed, and a bolus of dextrose was administered; however, a repeat blood glucose level was 2 mg per deciliter (0.1 mmol per liter). A continuous infusion of dextrose was started. Phototherapy and empirical treatment with ampicillin and gentamicin were administered.
During the next 3 days, the patient’s blood glucose level remained low, with a maximum level of 61 mg per deciliter (3.4 mmol per liter), even though the glucose infusion rate was increased and enteral feeding with formula was initiated. On the fourth day of life, she was transferred to the neonatal ICU of this hospital for further treatment.
On admission to the neonatal ICU, additional history was obtained. Before the ultrasonographic survey at 34 weeks of gestation, the pregnancy had been normal. The patient’s mother had taken prenatal vitamins. Prenatal maternal screening had been negative for gonorrhea, chlamydia, and syphilis, as well as human immunodeficiency virus, hepatitis B virus, and group B streptococcal infections; there was evidence of immunity to rubella virus. The maternal ABO blood type was AB, Rh positive. The newborn’s parents had immigrated to the United States from the Caribbean and now lived in a suburb in New England. The patient’s mother, father, and half brother were healthy.
On examination, the patient was alert and appeared comfortable. The temperature was 36.9°C, the heart rate 148 beats per minute, the blood pressure 79/45 mm Hg, the respiratory rate 49 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The anterior and posterior fontanelles were flat and soft. The lungs were clear on auscultation. The abdomen was soft without distention, tenderness, or palpable masses. Two sacral dimples with visible bases were noted. The female genitalia appeared normal, but the anus was displaced anteriorly.
Table 1.

Laboratory Data.
The blood glucose level was 60 mg per deciliter (3.3 mmol per liter) while the patient was receiving dextrose at a glucose infusion rate of 10.5 mg per kilogram of body weight per minute. The total bilirubin level was 20.4 mg per deciliter (349 μmol per liter). Other laboratory test results are shown in Table 1.
Figure 1.

Ultrasound Images of the Pelvis.
Figure 2.

MRI of the Pelvis.
Dr. Sjirk J. Westra: A chest radiograph showed clear lungs. Abdominal and pelvic ultrasonography (Figure 1) revealed a large solid–cystic mass anterior to the sacrum that measured 2.7 cm by 3.0 cm by 5.7 cm, with the rectum passing anteriorly to the mass. Results of spinal ultrasonography were normal, as were results of cranial ultrasonography performed through the anterior fontanelle. In addition, magnetic resonance imaging (MRI) of the abdomen, pelvis, and spine (Figure 2) showed a presacral solid–cystic mass that measured 2.7 cm by 2.8 cm by 5.9 cm, with a small extension into the ischiorectal fossa on the right side. There was no evidence of abdominal lymphadenopathy or involvement of the sacral spine.
Dr. Perez: During the next few days, the patient continued to receive dextrose at a high glucose infusion rate to maintain normoglycemia. At 5 days of life, a small bowel movement occurred. The blood lactate dehydrogenase level was 1173 U per liter (reference range, 110 to 210) and the beta human chorionic gonadotropin level 10.7 mIU per milliliter (reference range, <1.1).
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Congenital hyperinsulinism. The newborn girl presented with persistent hypoglycemia despite high glucose infusion rates and feeding, which is a key symptom of congenital hyperinsulinism. The condition is characterized by excessive insulin secretion, which leads to low blood glucose levels. The presence of a sacral dimple and an anteriorly displaced anus may suggest an associated genetic syndrome, but they are not directly related to the diagnosis of congenital hyperinsulinism. The elevated lactate dehydrogenase level may be a result of tissue hypoxia due to hypoglycemia. The beta human chorionic gonadotropin level is not relevant to this diagnosis. The presacral solid-cystic mass identified on imaging is likely unrelated to the hypoglycemia and may represent a separate condition.""
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        ""content"": ""The newborn girl presented with hypoglycemia that was resistant to high glucose infusion rates and enteral feeding. She also had a large solid-cystic mass anterior to the sacrum, with the rectum passing anteriorly to the mass. The blood lactate dehydrogenase level was elevated, which can be a sign of cell damage or disease. The beta human chorionic gonadotropin level was also elevated, which can be a sign of certain types of cancer in non-pregnant patients. Given these findings, the most likely diagnosis is sacrococcygeal teratoma. This is a type of tumor that is typically benign and is found at the base of the coccyx (tailbone). It is the most common tumor found in newborns. Hypoglycemia can occur in patients with sacrococcygeal teratoma due to the tumor's high metabolic demand.""
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        ""content"": ""This is a newborn girl who presents with hypoglycemia and a presacral solid-cystic mass. The differential diagnosis for this patient includes sacrococcygeal teratoma, anterior meningocele, and sacral chordoma. Sacrococcygeal teratoma is the most common tumor in newborns and can cause hypoglycemia due to the high metabolic demand of the tumor. Anterior meningocele is a type of spina bifida that can present with a sacral mass, but it is usually associated with neurologic symptoms, which this patient does not have. Sacral chordoma is a rare malignant bone tumor that can present with a sacral mass, but it is extremely rare in newborns and does not typically cause hypoglycemia. Given the patient's age, the presence of hypoglycemia, and the imaging findings, sacrococcygeal teratoma is the most likely diagnosis.\n\nDiagnosis: Sacrococcygeal teratoma.""
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10.1056/NEJMcpc2201236,Case 29-2022: A 33-Year-Old Man with Chronic Diarrhea and Autoimmune Enteropathy,"Hemoglobin (g/dl)	 	17.9
Hematocrit (%)	 	53.9
Platelet count (per μl)	 	244,000
White-cell count (per μl)	 	13,680
Differential count (per μl)		
Neutrophils	 	10,670
Lymphocytes	 	1560
Monocytes	 	1130
Eosinophils	 	80
Basophils	 00	70
Sodium (mmol/liter)	 	142
Potassium (mmol/liter)	 	3.8
Chloride (mmol/liter)	 	107
Carbon dioxide (mmol/liter)	 	21
Anion gap (mmol/liter)	 	14
Urea nitrogen (mg/dl)	 	14
Creatinine (mg/dl)	 	0.78
Alanine aminotransferase (U/liter)	 	32
Aspartate aminotransferase (U/liter)	 	23
Alkaline phosphatase (U/liter)	 	167
Albumin (g/dl)	 	3.9
Total protein (g/dl)	6. .3	6.4
IgA (mg/dl)	 	356
IgG (mg/dl)	 	900
IgM (mg/dl)	 	108
IgE (IU/ml)	0–100	664
Vitamin A (μg/dl)	32.5–78.0	28.8
Vitamin E (mg/liter)	5.5–17.0	7.1
Vitamin B12 (pg/ml)	>231	155
Vitamin D (ng/ml)	2 0	6
Zinc (μg/ml)	0.66–1.10	0.57
Erythrocyte sedimentation rate (mm/hr)	 	2","Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.",Inborn error of immunity.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 33-year-old man was evaluated in the gastroenterology clinic of this hospital because of relapsing chronic diarrhea and a diagnosis of autoimmune enteropathy.

Diarrhea had initially developed in the patient during infancy. When the patient was 2 months of age, he had poor growth and frequent bowel movements with loose stools. When he began to eat solid foods, diarrhea continued, and a hydrolyzed-protein diet was started. His parents were instructed to remove dairy, soy, and gluten from his diet, but diarrhea did not abate. Allergy skin-prick testing with cow’s milk and soy antigens was negative.

When the patient was 10 months of age, failure to thrive and diarrhea persisted, and generalized edema and nephrotic syndrome developed. Esophagogastroduodenoscopy (EGD) was performed, and histopathological examination of a small-intestinal biopsy specimen reportedly revealed villous atrophy, crypt hyperplasia, and diffuse inflammation. Transmission electron microscopy reportedly showed mild degenerative changes of the surface epithelium and mild focal microvillous atrophy; there were no immune deposits, and the basement membrane was normal.

Renal biopsy was also performed, and histopathological examination of a renal biopsy specimen revealed glomeruli with diffuse thickening of the basement membrane; there was no proliferation of cells or mesangial matrix. Transmission electron microscopy showed total effacement of the epithelial cell foot processes and an irregularly thickened glomerular basement membrane with numerous subepithelial and intramembranous electron-dense deposits. The patient received a working diagnosis of nephrotic syndrome due to membranous glomerulonephritis, and treatment with prednisone was started.

Diarrhea abated, proteinuria and generalized edema resolved, and growth resumed. However, during the next 2 years, intermittent relapses of diarrhea and nephrotic syndrome occurred when the dose of prednisone was decreased. When the patient was 3 years of age, treatment with chlorambucil was started for recurrent membranous glomerulonephritis, and there were no relapses for 1 year.

When the patient was 4 years of age, there was a recurrence of diarrhea associated with fever and hemolytic anemia. Stool culture, stool testing for Clostridioides difficile toxin, and examination of the stool for ova and parasites were all negative. EGD was performed, and histopathological examination of a small-intestinal biopsy specimen reportedly revealed villous atrophy, crypt hyperplasia, and active enteritis. The blood IgE level was 501 IU per milliliter (reference range, 0 to 100). The blood level of endomysial antibodies was not elevated, but anti–epithelial cell antibodies were detected. The patient received a diagnosis of autoimmune enteropathy, and treatment with intravenous glucocorticoids and cyclosporine was begun.

After several months, treatment with glucocorticoids and cyclosporine was stopped, and tacrolimus was begun. Tacrolimus was stopped after several years, when the patient’s symptoms resolved. From 5 to 13 years of age, he had no enteropathy, anemia, or nephropathy.

Beginning at 13 years of age, the patient was hospitalized for recurrences of diarrhea and nephropathy every 2 to 4 years during the 20 years before this evaluation. Six years before this evaluation, EGD and colonoscopy were performed, and the duodenal and colonic mucosa appeared diffusely edematous. Biopsy specimens were obtained.

Figure 1.

Small-Intestinal Biopsy Specimens.
Dr. Stuti G. Shroff: Examination of a duodenal biopsy specimen (Figure 1) revealed marked villous blunting, an increase in lymphoplasmacytic inflammatory cells in the lamina propria (known as lymphoplasmacytic expansion of the lamina propria), and a patchy increase in intraepithelial lymphocytes. Examination of a colonic biopsy specimen revealed mild focal active colitis that spared the rectum.

Dr. Hatipoglu: Treatment with intravenous methylprednisolone was begun, and diarrhea abated. For the next 2 years, relapses of diarrhea and nephrotic syndrome were treated with intravenous methylprednisolone or oral prednisone in combination with cyclosporine, tacrolimus, and mycophenolate mofetil.

Four years before this evaluation, antibodies against the M-type phospholipase A2 receptor were not detected. Renal biopsy was performed, and histopathological examination of a renal biopsy specimen again revealed evidence of membranous glomerulonephritis. Treatment was changed to prednisone, budesonide, and abatacept, and symptoms abated. After 2 years, the patient stopped taking abatacept. After another 2 years, diarrhea recurred, and the patient was referred to the gastroenterology clinic of this hospital.

In the gastroenterology clinic, additional history was obtained. There was a history of hypertension, gallstones, and rosacea. Eczema had developed when the patient was 10 months of age and had occurred intermittently into adulthood; it had abated with the administration of immunosuppressive agents. Anaphylactic shock had occurred when the patient was 2 years of age after he had been exposed to uncooked egg. At that time, allergy testing was performed, and the patient’s parents were instructed to remove eggs, tree nuts, peanuts, fish, and shellfish from his diet, in addition to removing dairy, soy, and gluten.

Current medications included prednisone, budesonide, and losartan. There were no known drug allergies. The patient lived in a Mid-Atlantic state and worked as a salesperson. He did not smoke tobacco and drank beer rarely. His family history included ovarian cancer in his mother and skin cancer in his father; his brother was healthy.

Table 1.

Laboratory Data.
On examination, the temperature was 37.0°C, the blood pressure 131/94 mm Hg, the heart rate 106 beats per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.1. The patient had short stature and diffuse erythema of the face and neck. There was mild tenderness in the left lower abdomen. The results of a lactulose breath test were normal, as was the fecal calprotectin level. Testing for antibodies to tissue transglutaminase was negative. Other laboratory test results are shown in Table 1. EGD and colonoscopy were performed, and the findings were consistent with duodenitis, gastritis, and atrophy of the colon. Biopsy specimens were obtained.

Dr. Shroff: Histopathological examination of ileal and duodenal biopsy specimens (Figure 1) revealed villous blunting, lymphoplasmacytic expansion of the lamina propria, and intraepithelial lymphocytosis.

Dr. Hatipoglu: A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 33-year-old man was evaluated in the gastroenterology clinic of this hospital because of relapsing chronic diarrhea and a diagnosis of autoimmune enteropathy.

Diarrhea had initially developed in the patient during infancy. When the patient was 2 months of age, he had poor growth and frequent bowel movements with loose stools. When he began to eat solid foods, diarrhea continued, and a hydrolyzed-protein diet was started. His parents were instructed to remove dairy, soy, and gluten from his diet, but diarrhea did not abate. Allergy skin-prick testing with cow’s milk and soy antigens was negative.

When the patient was 10 months of age, failure to thrive and diarrhea persisted, and generalized edema and nephrotic syndrome developed. Esophagogastroduodenoscopy (EGD) was performed, and histopathological examination of a small-intestinal biopsy specimen reportedly revealed villous atrophy, crypt hyperplasia, and diffuse inflammation. Transmission electron microscopy reportedly showed mild degenerative changes of the surface epithelium and mild focal microvillous atrophy; there were no immune deposits, and the basement membrane was normal.

Renal biopsy was also performed, and histopathological examination of a renal biopsy specimen revealed glomeruli with diffuse thickening of the basement membrane; there was no proliferation of cells or mesangial matrix. Transmission electron microscopy showed total effacement of the epithelial cell foot processes and an irregularly thickened glomerular basement membrane with numerous subepithelial and intramembranous electron-dense deposits. The patient received a working diagnosis of nephrotic syndrome due to membranous glomerulonephritis, and treatment with prednisone was started.

Diarrhea abated, proteinuria and generalized edema resolved, and growth resumed. However, during the next 2 years, intermittent relapses of diarrhea and nephrotic syndrome occurred when the dose of prednisone was decreased. When the patient was 3 years of age, treatment with chlorambucil was started for recurrent membranous glomerulonephritis, and there were no relapses for 1 year.

When the patient was 4 years of age, there was a recurrence of diarrhea associated with fever and hemolytic anemia. Stool culture, stool testing for Clostridioides difficile toxin, and examination of the stool for ova and parasites were all negative. EGD was performed, and histopathological examination of a small-intestinal biopsy specimen reportedly revealed villous atrophy, crypt hyperplasia, and active enteritis. The blood IgE level was 501 IU per milliliter (reference range, 0 to 100). The blood level of endomysial antibodies was not elevated, but anti–epithelial cell antibodies were detected. The patient received a diagnosis of autoimmune enteropathy, and treatment with intravenous glucocorticoids and cyclosporine was begun.

After several months, treatment with glucocorticoids and cyclosporine was stopped, and tacrolimus was begun. Tacrolimus was stopped after several years, when the patient’s symptoms resolved. From 5 to 13 years of age, he had no enteropathy, anemia, or nephropathy.

Beginning at 13 years of age, the patient was hospitalized for recurrences of diarrhea and nephropathy every 2 to 4 years during the 20 years before this evaluation. Six years before this evaluation, EGD and colonoscopy were performed, and the duodenal and colonic mucosa appeared diffusely edematous. Biopsy specimens were obtained.

Figure 1.

Small-Intestinal Biopsy Specimens.
Dr. Stuti G. Shroff: Examination of a duodenal biopsy specimen (Figure 1) revealed marked villous blunting, an increase in lymphoplasmacytic inflammatory cells in the lamina propria (known as lymphoplasmacytic expansion of the lamina propria), and a patchy increase in intraepithelial lymphocytes. Examination of a colonic biopsy specimen revealed mild focal active colitis that spared the rectum.

Dr. Hatipoglu: Treatment with intravenous methylprednisolone was begun, and diarrhea abated. For the next 2 years, relapses of diarrhea and nephrotic syndrome were treated with intravenous methylprednisolone or oral prednisone in combination with cyclosporine, tacrolimus, and mycophenolate mofetil.

Four years before this evaluation, antibodies against the M-type phospholipase A2 receptor were not detected. Renal biopsy was performed, and histopathological examination of a renal biopsy specimen again revealed evidence of membranous glomerulonephritis. Treatment was changed to prednisone, budesonide, and abatacept, and symptoms abated. After 2 years, the patient stopped taking abatacept. After another 2 years, diarrhea recurred, and the patient was referred to the gastroenterology clinic of this hospital.

In the gastroenterology clinic, additional history was obtained. There was a history of hypertension, gallstones, and rosacea. Eczema had developed when the patient was 10 months of age and had occurred intermittently into adulthood; it had abated with the administration of immunosuppressive agents. Anaphylactic shock had occurred when the patient was 2 years of age after he had been exposed to uncooked egg. At that time, allergy testing was performed, and the patient’s parents were instructed to remove eggs, tree nuts, peanuts, fish, and shellfish from his diet, in addition to removing dairy, soy, and gluten.

Current medications included prednisone, budesonide, and losartan. There were no known drug allergies. The patient lived in a Mid-Atlantic state and worked as a salesperson. He did not smoke tobacco and drank beer rarely. His family history included ovarian cancer in his mother and skin cancer in his father; his brother was healthy.

Table 1.

Laboratory Data.
On examination, the temperature was 37.0°C, the blood pressure 131/94 mm Hg, the heart rate 106 beats per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.1. The patient had short stature and diffuse erythema of the face and neck. There was mild tenderness in the left lower abdomen. The results of a lactulose breath test were normal, as was the fecal calprotectin level. Testing for antibodies to tissue transglutaminase was negative. Other laboratory test results are shown in Table 1. EGD and colonoscopy were performed, and the findings were consistent with duodenitis, gastritis, and atrophy of the colon. Biopsy specimens were obtained.

Dr. Shroff: Histopathological examination of ileal and duodenal biopsy specimens (Figure 1) revealed villous blunting, lymphoplasmacytic expansion of the lamina propria, and intraepithelial lymphocytosis.

Dr. Hatipoglu: A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Autoimmune enteropathy with membranous glomerulonephritis. The patient has a history of chronic diarrhea and nephrotic syndrome since infancy. The diarrhea did not respond to dietary changes, suggesting it was not due to food allergies or intolerances. Biopsies of the small intestine showed villous atrophy, crypt hyperplasia, and inflammation, which are characteristic of autoimmune enteropathy. The patient also had nephrotic syndrome with biopsy findings consistent with membranous glomerulonephritis, another autoimmune condition. The patient's symptoms improved with immunosuppressive therapy, further supporting an autoimmune etiology.""
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        ""content"": ""The patient is a 33-year-old man with a history of chronic diarrhea, failure to thrive, and nephrotic syndrome since infancy. He has been diagnosed with autoimmune enteropathy and has had recurrent episodes of diarrhea and nephropathy. His symptoms have been responsive to immunosuppressive therapy. The differential diagnosis for this patient includes autoimmune enteropathy, celiac disease, inflammatory bowel disease, and food allergies. Celiac disease is less likely given the negative testing for antibodies to tissue transglutaminase and the lack of response to a gluten-free diet. Inflammatory bowel disease is also less likely given the lack of typical endoscopic findings and the presence of nephrotic syndrome, which is not typically associated with inflammatory bowel disease. Food allergies could potentially cause diarrhea, but would not explain the nephrotic syndrome. The patient's history of response to immunosuppressive therapy, the presence of anti\u2013epithelial cell antibodies, and the histopathological findings on biopsy are all consistent with autoimmune enteropathy. \n\nDiagnosis: Autoimmune enteropathy.""
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10.1056/NEJMcpc2100271,Case 28-2022: A 59-Year-Old Man with Headache and Progressive Neurologic Dysfunction,,Granulomatosis with polyangiitis.,Granulomatosis with polyangiitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 59-year-old man was evaluated in the rheumatology clinic of this hospital because of headache and progressive neurologic dysfunction.

Ten months before this evaluation, daily fever with a temperature of up to 38.9°C, chills, myalgias, drenching night sweats, and pressure and pain in both cheeks and ears developed. The patient was evaluated by his primary care physician. He reported rhinorrhea and fatigue but no headache, pharyngitis, or dyspnea, and he had no sick contacts. On examination, the temperature was 37.8°C, the heart rate 100 beats per minute, the blood pressure 112/64 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. He was ill-appearing, and the maxillary sinuses were tender on palpation; the remainder of the examination was normal. Blood levels of electrolytes, calcium, total protein, albumin, and globulin were normal, as were the results of kidney-function tests. The platelet count was 463,000 per microliter (reference range, 140,000 to 400,000); the remainder of the complete blood count and the differential count were normal. Amoxicillin–clavulanate was prescribed.

During the next 2 weeks, fever, night sweats, and sinus and facial pain continued. Diffuse headache developed, along with jaw soreness, scalp tenderness, and hip and shoulder stiffness. The patient was evaluated again by his primary care physician. He reported weight loss of 2 kg, episodic double vision, and hip pain that caused difficulty in standing and climbing stairs. The physical examination was unchanged. Urinalysis was normal. A test for heterophile antibody and an interferon-γ release assay for Mycobacterium tuberculosis were negative, as were screening tests for human immunodeficiency virus and Lyme disease. Chest radiography and computed tomography of the sinuses were normal. The patient was referred to a rheumatologist at another hospital.

On evaluation, the patient reported persistent fever and frontal, temporal, and maxillary headache. There were palpable temporal artery pulses without tenderness; the remainder of the examination was normal, including the absence of bruits on auscultation of large vessels. The erythrocyte sedimentation rate was 108 mm per hour (reference range, 0 to 20), the blood level of C-reactive protein greater than 100 mg per liter (reference value,  .0), the blood level of rheumatoid factor 24 IU per milliliter (reference value, <14), and the blood level of aldolase 8.4 IU per milliliter (reference value,  .1). Biopsy of the right temporal artery was performed. Histologic examination of the biopsy specimen reportedly showed no granulomas, but evidence of chronic inflammation of the temporal artery and fibrinoid necrosis of an adjacent small vessel were noted.

A diagnosis of giant-cell arteritis was made, and treatment with prednisone was started. Within a few days after initiation of treatment, headache, fever, jaw pain, and joint stiffness abated. The next month, an attempt to lower the prednisone dose resulted in recurrent severe headache with scalp tenderness, jaw pain, and hip stiffness. The erythrocyte sedimentation rate was 55 mm per hour and the C-reactive protein level 84 mg per liter. Treatment with weekly subcutaneous administration of tocilizumab was initiated.

During the next 6 weeks, another attempt was made to taper the prednisone dose. After 1 week of treatment at a lower prednisone dose, and 5 months after the development of initial symptoms (5 months before the current evaluation), the patient reported headache that he described as “the worst headache of my life,” with associated jaw pain and diplopia. The pain was worst at the right frontal and maxillary areas, but the entire right side of the face, including the scalp and neck, was affected. The patient returned to the other hospital for evaluation. He was found to have palsies of the third and sixth cranial nerves on the right side. The patient was admitted to the neurology service at the other hospital. Antineutrophil cytoplasmic antibody (ANCA) testing revealed a slightly elevated myeloperoxidase antibody level, at 1.9 U (reference value, <1.0), but antibodies to proteinase 3 were not detected. Blood levels of IgG subclasses were normal. Imaging studies were obtained.

Figure 1.

MRI of the Head and Spine Obtained 5 Months before the Current Evaluation.
Dr. Otto Rapalino: Magnetic resonance imaging (MRI) of the head (Figure 1A and 1B), performed after the administration of intravenous contrast material, revealed abnormal expansion and enhancement of the right cavernous sinus that extended into the right superior orbital fissure and right pterygopalatine fossa, as well as abnormal pachymeningeal thickening and enhancement of the adjacent right middle cranial fossa. MRI of the cervical spine (Figure 1C and 1D) showed masslike pachymeningeal thickening and enhancement in the upper cervical spinal canal at C2–C4 with an anterior predominance as well as more circumferentially at the cervicothoracic junction (C6–T3) with a posterior predominance, with resultant canal narrowing and mild cord compression at C7–T2. There was no spinal cord edema.

Dr. John Stone: A lumbar puncture was performed; an opening pressure was not recorded. The cerebrospinal fluid (CSF) glucose level was 65 mg per deciliter (3.6 mmol per liter; reference range, 50 to 80 mg per deciliter [2.8 to 4.4 mmol per liter]), and the protein level was 126 mg per deciliter (reference range, 15 to 45), with 2 red cells per microliter and 8 white cells per microliter (of which 79% were lymphocytes). Gram’s staining and cultures of the CSF were negative. Tests for CSF myelin basic protein, angiotensin-converting enzyme, cryptococcal antigen, cysticercosis IgG, mycobacterial DNA, Epstein–Barr virus DNA, and borrelia DNA were negative, as was a Venereal Disease Research Laboratory test. Cytologic analysis of the CSF showed a mixed population of mononuclear cells with rare plasma cells. The CSF immunoglobulin level was 19 mg per deciliter (reference range, 0 to 6), with 5 oligoclonal bands.

On the eighth hospital day, a meningeal biopsy was performed. Treatment with high-dose prednisone was started, and the patient was discharged home. During the next 2 weeks, the patient continued taking the prednisone, but the facial and head pain worsened. He was readmitted to the other hospital to receive 3 days of treatment with parenteral pulse-dose methylprednisolone.

Pathological examination of the meningeal biopsy specimen revealed a densely fibrotic, chronically inflamed dura mater with large numbers of CD68+ macrophages and CD3+ T lymphocytes and with focal collections of CD20+ B lymphocytes. There was a large number of polyclonal plasma cells with more than 100 IgG4+ plasma cells per high-power field. Storiform fibrosis was present, and elastin staining revealed obliterative venulitis. Some of the inflammatory foci were angiocentric, but no vasculitis was present. There were rare foci of fibrinoid necrosis and some neutrophils, with rare giant cells but no granulomas. A diagnosis of IgG4-related disease was made, and rituximab was administered. Two days after the first rituximab dose, a pulmonary embolism was diagnosed, and treatment with apixaban was initiated. Two weeks later, repeat imaging was obtained to evaluate the treatment response.

Figure 2.

MRI of the Head and Spine Obtained 4 Months before the Current Evaluation.
Dr. Rapalino: Repeat MRI of the head (Figure 2A and 2B), performed after the administration of intravenous contrast material, revealed increased abnormal enhancement in the right cavernous sinus and right middle cranial fossa and new abnormal enhancement in the left cavernous sinus and adjacent left middle cranial fossa. MRI of the cervical spine (Figure 2C and 2D) also showed progression in the extent and thickness of the ventral and dorsal pachymeningeal thickening and enhancement. There was also progression of the canal stenosis, which had become severe, and cord compression at the C7 level. There was no cord signal abnormality.

Dr. John Stone: The patient received a second infusion of rituximab, as well as treatment with oral dexamethasone. Three weeks later, and 7 months after the development of initial symptoms (3 months before the current evaluation), the patient was admitted to the other hospital because of worsening headache, nausea, and vomiting. Examination was notable for new sensorineural hearing loss in the right ear and deviation of the tongue to the left. A ventriculoperitoneal shunt was placed. Treatment with dexamethasone was continued, and the patient was discharged home. Three weeks after placement of the ventriculoperitoneal shunt, the patient was admitted again to the other hospital because of streptococcal infection. Two months after discharge, and 10 months after the development of initial symptoms, he was seen in the rheumatology clinic of this hospital for additional evaluation.

The patient had a history of migraines, hypertension, and a heterozygous factor V Leiden mutation. Medications included apixaban, baclofen, dexamethasone, furosemide, gabapentin, lisinopril, and metoprolol. He was a retired businessman and lived with his wife. He drank one glass of wine weekly and had quit smoking more than 40 years before the current evaluation. His maternal grandfather had died from a ruptured aortic aneurysm.

The temperature was 36.5°C, the heart rate 88 beats per minute, the blood pressure 118/79 mm Hg, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.8. The scalp hair was thin. He had cushingoid facies; acne on the face, back, and chest; striae on the flanks; and proximal muscle weakness of the arms and legs. There was no scalp or temporal tenderness. He had no tongue lesions or oral ulcers, and the nasal examination showed no crusting. Extraocular movements were intact. There was no arthritis. The chest, abdominal, and neurologic examinations were normal. The complete blood count and the differential count were normal, as was a urinalysis. The erythrocyte sedimentation rate was 52 mm per hour and the C-reactive protein level 5 mg per liter. Serum protein electrophoresis revealed an IgM level of 22 mg per deciliter (reference range, 53 to 334) and normal levels of IgG and IgA. ANCA testing was negative.

A diagnosis and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 59-year-old man was evaluated in the rheumatology clinic of this hospital because of headache and progressive neurologic dysfunction.

Ten months before this evaluation, daily fever with a temperature of up to 38.9°C, chills, myalgias, drenching night sweats, and pressure and pain in both cheeks and ears developed. The patient was evaluated by his primary care physician. He reported rhinorrhea and fatigue but no headache, pharyngitis, or dyspnea, and he had no sick contacts. On examination, the temperature was 37.8°C, the heart rate 100 beats per minute, the blood pressure 112/64 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. He was ill-appearing, and the maxillary sinuses were tender on palpation; the remainder of the examination was normal. Blood levels of electrolytes, calcium, total protein, albumin, and globulin were normal, as were the results of kidney-function tests. The platelet count was 463,000 per microliter (reference range, 140,000 to 400,000); the remainder of the complete blood count and the differential count were normal. Amoxicillin–clavulanate was prescribed.

During the next 2 weeks, fever, night sweats, and sinus and facial pain continued. Diffuse headache developed, along with jaw soreness, scalp tenderness, and hip and shoulder stiffness. The patient was evaluated again by his primary care physician. He reported weight loss of 2 kg, episodic double vision, and hip pain that caused difficulty in standing and climbing stairs. The physical examination was unchanged. Urinalysis was normal. A test for heterophile antibody and an interferon-γ release assay for Mycobacterium tuberculosis were negative, as were screening tests for human immunodeficiency virus and Lyme disease. Chest radiography and computed tomography of the sinuses were normal. The patient was referred to a rheumatologist at another hospital.

On evaluation, the patient reported persistent fever and frontal, temporal, and maxillary headache. There were palpable temporal artery pulses without tenderness; the remainder of the examination was normal, including the absence of bruits on auscultation of large vessels. The erythrocyte sedimentation rate was 108 mm per hour (reference range, 0 to 20), the blood level of C-reactive protein greater than 100 mg per liter (reference value,  .0), the blood level of rheumatoid factor 24 IU per milliliter (reference value, <14), and the blood level of aldolase 8.4 IU per milliliter (reference value,  .1). Biopsy of the right temporal artery was performed. Histologic examination of the biopsy specimen reportedly showed no granulomas, but evidence of chronic inflammation of the temporal artery and fibrinoid necrosis of an adjacent small vessel were noted.

A diagnosis of giant-cell arteritis was made, and treatment with prednisone was started. Within a few days after initiation of treatment, headache, fever, jaw pain, and joint stiffness abated. The next month, an attempt to lower the prednisone dose resulted in recurrent severe headache with scalp tenderness, jaw pain, and hip stiffness. The erythrocyte sedimentation rate was 55 mm per hour and the C-reactive protein level 84 mg per liter. Treatment with weekly subcutaneous administration of tocilizumab was initiated.

During the next 6 weeks, another attempt was made to taper the prednisone dose. After 1 week of treatment at a lower prednisone dose, and 5 months after the development of initial symptoms (5 months before the current evaluation), the patient reported headache that he described as “the worst headache of my life,” with associated jaw pain and diplopia. The pain was worst at the right frontal and maxillary areas, but the entire right side of the face, including the scalp and neck, was affected. The patient returned to the other hospital for evaluation. He was found to have palsies of the third and sixth cranial nerves on the right side. The patient was admitted to the neurology service at the other hospital. Antineutrophil cytoplasmic antibody (ANCA) testing revealed a slightly elevated myeloperoxidase antibody level, at 1.9 U (reference value, <1.0), but antibodies to proteinase 3 were not detected. Blood levels of IgG subclasses were normal. Imaging studies were obtained.

Figure 1.

MRI of the Head and Spine Obtained 5 Months before the Current Evaluation.
Dr. Otto Rapalino: Magnetic resonance imaging (MRI) of the head (Figure 1A and 1B), performed after the administration of intravenous contrast material, revealed abnormal expansion and enhancement of the right cavernous sinus that extended into the right superior orbital fissure and right pterygopalatine fossa, as well as abnormal pachymeningeal thickening and enhancement of the adjacent right middle cranial fossa. MRI of the cervical spine (Figure 1C and 1D) showed masslike pachymeningeal thickening and enhancement in the upper cervical spinal canal at C2–C4 with an anterior predominance as well as more circumferentially at the cervicothoracic junction (C6–T3) with a posterior predominance, with resultant canal narrowing and mild cord compression at C7–T2. There was no spinal cord edema.

Dr. John Stone: A lumbar puncture was performed; an opening pressure was not recorded. The cerebrospinal fluid (CSF) glucose level was 65 mg per deciliter (3.6 mmol per liter; reference range, 50 to 80 mg per deciliter [2.8 to 4.4 mmol per liter]), and the protein level was 126 mg per deciliter (reference range, 15 to 45), with 2 red cells per microliter and 8 white cells per microliter (of which 79% were lymphocytes). Gram’s staining and cultures of the CSF were negative. Tests for CSF myelin basic protein, angiotensin-converting enzyme, cryptococcal antigen, cysticercosis IgG, mycobacterial DNA, Epstein–Barr virus DNA, and borrelia DNA were negative, as was a Venereal Disease Research Laboratory test. Cytologic analysis of the CSF showed a mixed population of mononuclear cells with rare plasma cells. The CSF immunoglobulin level was 19 mg per deciliter (reference range, 0 to 6), with 5 oligoclonal bands.

On the eighth hospital day, a meningeal biopsy was performed. Treatment with high-dose prednisone was started, and the patient was discharged home. During the next 2 weeks, the patient continued taking the prednisone, but the facial and head pain worsened. He was readmitted to the other hospital to receive 3 days of treatment with parenteral pulse-dose methylprednisolone.

Pathological examination of the meningeal biopsy specimen revealed a densely fibrotic, chronically inflamed dura mater with large numbers of CD68+ macrophages and CD3+ T lymphocytes and with focal collections of CD20+ B lymphocytes. There was a large number of polyclonal plasma cells with more than 100 IgG4+ plasma cells per high-power field. Storiform fibrosis was present, and elastin staining revealed obliterative venulitis. Some of the inflammatory foci were angiocentric, but no vasculitis was present. There were rare foci of fibrinoid necrosis and some neutrophils, with rare giant cells but no granulomas. A diagnosis of IgG4-related disease was made, and rituximab was administered. Two days after the first rituximab dose, a pulmonary embolism was diagnosed, and treatment with apixaban was initiated. Two weeks later, repeat imaging was obtained to evaluate the treatment response.

Figure 2.

MRI of the Head and Spine Obtained 4 Months before the Current Evaluation.
Dr. Rapalino: Repeat MRI of the head (Figure 2A and 2B), performed after the administration of intravenous contrast material, revealed increased abnormal enhancement in the right cavernous sinus and right middle cranial fossa and new abnormal enhancement in the left cavernous sinus and adjacent left middle cranial fossa. MRI of the cervical spine (Figure 2C and 2D) also showed progression in the extent and thickness of the ventral and dorsal pachymeningeal thickening and enhancement. There was also progression of the canal stenosis, which had become severe, and cord compression at the C7 level. There was no cord signal abnormality.

Dr. John Stone: The patient received a second infusion of rituximab, as well as treatment with oral dexamethasone. Three weeks later, and 7 months after the development of initial symptoms (3 months before the current evaluation), the patient was admitted to the other hospital because of worsening headache, nausea, and vomiting. Examination was notable for new sensorineural hearing loss in the right ear and deviation of the tongue to the left. A ventriculoperitoneal shunt was placed. Treatment with dexamethasone was continued, and the patient was discharged home. Three weeks after placement of the ventriculoperitoneal shunt, the patient was admitted again to the other hospital because of streptococcal infection. Two months after discharge, and 10 months after the development of initial symptoms, he was seen in the rheumatology clinic of this hospital for additional evaluation.

The patient had a history of migraines, hypertension, and a heterozygous factor V Leiden mutation. Medications included apixaban, baclofen, dexamethasone, furosemide, gabapentin, lisinopril, and metoprolol. He was a retired businessman and lived with his wife. He drank one glass of wine weekly and had quit smoking more than 40 years before the current evaluation. His maternal grandfather had died from a ruptured aortic aneurysm.

The temperature was 36.5°C, the heart rate 88 beats per minute, the blood pressure 118/79 mm Hg, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.8. The scalp hair was thin. He had cushingoid facies; acne on the face, back, and chest; striae on the flanks; and proximal muscle weakness of the arms and legs. There was no scalp or temporal tenderness. He had no tongue lesions or oral ulcers, and the nasal examination showed no crusting. Extraocular movements were intact. There was no arthritis. The chest, abdominal, and neurologic examinations were normal. The complete blood count and the differential count were normal, as was a urinalysis. The erythrocyte sedimentation rate was 52 mm per hour and the C-reactive protein level 5 mg per liter. Serum protein electrophoresis revealed an IgM level of 22 mg per deciliter (reference range, 53 to 334) and normal levels of IgG and IgA. ANCA testing was negative.

A diagnosis and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""IgG4-related disease. The patient's symptoms of fever, night sweats, sinus and facial pain, headache, jaw soreness, scalp tenderness, and hip and shoulder stiffness, along with the findings of abnormal enhancement in the right cavernous sinus and right middle cranial fossa, and the presence of large numbers of CD68+ macrophages and CD3+ T lymphocytes and with focal collections of CD20+ B lymphocytes in the meningeal biopsy, all point towards IgG4-related disease. This is a systemic disease that can affect any organ system, and is characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and often, but not always, elevated serum IgG4 concentration.""
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        ""content"": ""IgG4-related disease. The patient's symptoms of fever, night sweats, sinus and facial pain, headache, jaw soreness, scalp tenderness, and hip and shoulder stiffness, along with the lab findings of elevated erythrocyte sedimentation rate and C-reactive protein, initially suggested giant cell arteritis. However, the patient's symptoms did not improve with prednisone treatment, and further testing revealed an elevated myeloperoxidase antibody level and abnormal MRI findings. The meningeal biopsy showed a large number of CD68+ macrophages and CD3+ T lymphocytes, focal collections of CD20+ B lymphocytes, a large number of polyclonal plasma cells with more than 100 IgG4+ plasma cells per high-power field, and storiform fibrosis, which are all consistent with IgG4-related disease.""
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        ""content"": ""The patient is a 59-year-old man presenting with headache, progressive neurologic dysfunction, fever, myalgias, night sweats, and sinus and facial pain. He also reports weight loss, double vision, and hip pain. His symptoms initially improved with prednisone, suggesting an inflammatory or autoimmune process. The differential diagnosis includes giant cell arteritis, vasculitis, and IgG4-related disease. Giant cell arteritis was initially suspected due to the patient's age, headache, jaw pain, and elevated inflammatory markers. However, the patient's symptoms did not fully resolve with high-dose steroids, which is unusual for giant cell arteritis. Vasculitis could also explain the patient's symptoms, but the patient's ANCA test was only slightly elevated and his biopsy did not show granulomas, making this diagnosis less likely. Finally, IgG4-related disease could explain all of the patient's symptoms. This condition is a systemic inflammatory disease that can affect various organs and is characterized by tumefactive lesions and a lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells. The patient's biopsy showed a large number of IgG4+ plasma cells, storiform fibrosis, and obliterative venulitis, which are characteristic of IgG4-related disease. His symptoms did not fully resolve with steroids alone, but did improve with the addition of rituximab, which is consistent with this diagnosis.\n\nDiagnosis: IgG4-related disease.""
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10.1056/NEJMcpc2201246,"Case 27-2022: A 32-Year-Old Man with Confusion, Headache, and Fever","Hemoglobin (g/dl)	 	14.5
Hematocrit (%)	 	44.2
Mean corpuscular volume (fl)	 	91.3
White-cell count (per μl)	 	11,760
Differential count (per μl)		
Neutrophils	 	9430
Lymphocytes	 	1100
Monocytes	 	1080
Eosinophils	 	800
Basophils	 00	300
Platelet count (per μl)	 	208,000
Human immunodeficiency virus type 1 and type 2 antibody and antigen	Nonreactive	Nonreactive
Treponemal antibody	Nonreactive	Nonreactive
Cryptococcal antigen	Negative	Negative
Interferon-γ release assay for tuberculosis	Negative	Negative
C-reactive protein (mg/liter)	 .0	39.1
Erythrocyte sedimentation rate (mm/hr)	 	24",Encephalitis due to Beh‚àö√üet‚Äö√Ñ√¥s disease.,Neuro-Behçet’s disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 32-year-old man was admitted to this hospital after 2 weeks of confusion and headache and 2 days of fever.

The patient had been in his usual state of health until 1 month before admission, when his wife noted that he began to have behavior suggestive of anxiety. Two weeks before admission, his wife noted that he began to have confusion; for example, he was unable to recall the ages of his children or to correctly identify the date. At that time, headache and neck stiffness developed. Two days before admission, fever developed. On the day of admission, the patient had worsening confusion and somnolence, and his wife brought him to the emergency department of this hospital for evaluation.

On presentation, the patient was not able to provide any history but was accompanied by his wife, who described his recent symptoms. His medical record showed a 10-year history of Behçet’s disease, which had initially been complicated by oral and genital ulcers and intermittent fever. During the following decade, flares of Behçet’s disease had been associated with various manifestations: pulmonary embolism, iliac artery aneurysm and dissection, bilateral renal vein thrombosis, erythema nodosum, deep venous thrombosis, uveitis, an inferior vena cava clot complicated by superior vena cava syndrome that led to thrombectomy, and renal infarction. The flares of Behçet’s disease had usually included oral ulcers, genital ulcers, uveitis, or fever.

Past treatment for Behçet’s disease had included azathioprine, cyclosporine, and prednisone. Two years before this presentation, treatment with azathioprine and cyclosporine was discontinued and adalimumab initiated. Attempts to taper the dose of prednisone resulted in flares of genital and oral ulcers. The frequency of adalimumab administration was increased to weekly, but genital and oral ulcers persisted. Thirteen months before this presentation, treatment with adalimumab was stopped and infliximab initiated. Diffuse arthralgias developed that were attributed to infliximab. Twelve months before this presentation, treatment with infliximab was stopped and golimumab initiated.

Other medical history included an episode of lymphocyte-predominant meningitis, which had been diagnosed during an evaluation for headache, fever, and neck pain 17 months before this presentation. During the episode, there was a 72-hour delay in performing lumbar puncture for cerebrospinal fluid (CSF) analysis because the patient had been taking apixaban for the treatment of venous thromboembolism. While he was awaiting lumbar puncture, broad-spectrum antibiotic agents were administered, and the headache, fever, and neck pain resolved. CSF analysis revealed normal levels of glucose and total protein, no red cells, and a nucleated-cell count of 88 per microliter (reference range, 0 to 5), with 97% lymphocytes and 3% monocytes. Nucleic acid amplification testing for herpes simplex virus type 1 and type 2 DNA was negative, and Gram’s staining revealed no organisms. Antimicrobial therapy was discontinued, and the patient was discharged home.

There was also a history of coronavirus disease 2019, which had been diagnosed 16 months before this presentation. Current medications included golimumab, apixaban, prednisone, and trimethoprim–sulfamethoxazole. There were no known allergies. The patient lived with his wife and four children. He had previously worked in construction; he had been released from prison 3 months before this presentation and was not currently working. He had a remote history of smoking tobacco; he did not drink alcohol or use illicit drugs. His grandmother had hypertension.

On examination in the emergency department, the patient was somnolent but arose in response to verbal stimuli. His level of alertness fluctuated, he was only intermittently able to answer simple questions, and he could not provide a coherent history of his illness. The temperature was 39.5°C, the blood pressure 122/71 mm Hg, the heart rate 81 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 96% while he was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 29.7. He was oriented to person and place but not to time. There was no neck stiffness. Mild injection in the left eye was present, but there were no oral or skin lesions. The patient was not able to participate fully in a neurologic examination, but he was able to move his arms and legs; no focal neurologic findings were noted on observation. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Blood levels of glucose and electrolytes were normal, as were results of liver-function, kidney-function, and coagulation tests. Other laboratory test results are shown in Table 1. Urinalysis revealed trace ketones but was otherwise normal. The blood acetaminophen level was less than 5.0 μg per milliliter (reference range, 0.0 to 25.0); blood testing for ethanol was negative. Testing of a nasopharyngeal swab specimen for respiratory viral pathogens was positive for human rhinovirus or enterovirus. Blood specimens were obtained for culture. Imaging studies were obtained.

Dr. Pamela W. Schaefer: A chest radiograph was normal. Computed tomography (CT) of the head revealed mucosal thickening with layering fluid levels in both maxillary sinuses, but the study was otherwise normal. CT angiography of the head and neck, performed with and without the administration of intravenous contrast material, revealed normal arterial and venous vasculature.

Dr. Suarez: Treatment with vancomycin, ceftriaxone, ampicillin, and acyclovir was initiated. The patient was admitted to the hospital. Treatment with apixaban was stopped and heparin administered intravenously in anticipation of performing a lumbar puncture. Fever and headache abated, but the patient’s mental status did not improve. Blood cultures showed no growth. On the fourth hospital day, a lumbar puncture was performed. The opening pressure was not obtained. CSF analysis revealed a normal total protein level, a glucose level of 40 mg per deciliter (2.2 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]), a red-cell count of 2 per microliter (reference range, 0 to 5), and a nucleated-cell count of 284 per microliter (reference range, 0 to 5), with 72% lymphocytes, 13% neutrophils, 11% monocytes, and 4% unclassified cells. Nucleic acid amplification testing for herpes simplex virus type 1 and type 2 DNA was negative, and Gram’s staining revealed no organisms. No acid-fast bacilli were observed on a mycobacterial smear, and no fungi were seen on examination of a fungal wet preparation. Testing of the CSF for cryptococcal antigen and enterovirus RNA was negative.

Additional diagnostic testing was performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 32-year-old man was admitted to this hospital after 2 weeks of confusion and headache and 2 days of fever.

The patient had been in his usual state of health until 1 month before admission, when his wife noted that he began to have behavior suggestive of anxiety. Two weeks before admission, his wife noted that he began to have confusion; for example, he was unable to recall the ages of his children or to correctly identify the date. At that time, headache and neck stiffness developed. Two days before admission, fever developed. On the day of admission, the patient had worsening confusion and somnolence, and his wife brought him to the emergency department of this hospital for evaluation.

On presentation, the patient was not able to provide any history but was accompanied by his wife, who described his recent symptoms. His medical record showed a 10-year history of Behçet’s disease, which had initially been complicated by oral and genital ulcers and intermittent fever. During the following decade, flares of Behçet’s disease had been associated with various manifestations: pulmonary embolism, iliac artery aneurysm and dissection, bilateral renal vein thrombosis, erythema nodosum, deep venous thrombosis, uveitis, an inferior vena cava clot complicated by superior vena cava syndrome that led to thrombectomy, and renal infarction. The flares of Behçet’s disease had usually included oral ulcers, genital ulcers, uveitis, or fever.

Past treatment for Behçet’s disease had included azathioprine, cyclosporine, and prednisone. Two years before this presentation, treatment with azathioprine and cyclosporine was discontinued and adalimumab initiated. Attempts to taper the dose of prednisone resulted in flares of genital and oral ulcers. The frequency of adalimumab administration was increased to weekly, but genital and oral ulcers persisted. Thirteen months before this presentation, treatment with adalimumab was stopped and infliximab initiated. Diffuse arthralgias developed that were attributed to infliximab. Twelve months before this presentation, treatment with infliximab was stopped and golimumab initiated.

Other medical history included an episode of lymphocyte-predominant meningitis, which had been diagnosed during an evaluation for headache, fever, and neck pain 17 months before this presentation. During the episode, there was a 72-hour delay in performing lumbar puncture for cerebrospinal fluid (CSF) analysis because the patient had been taking apixaban for the treatment of venous thromboembolism. While he was awaiting lumbar puncture, broad-spectrum antibiotic agents were administered, and the headache, fever, and neck pain resolved. CSF analysis revealed normal levels of glucose and total protein, no red cells, and a nucleated-cell count of 88 per microliter (reference range, 0 to 5), with 97% lymphocytes and 3% monocytes. Nucleic acid amplification testing for herpes simplex virus type 1 and type 2 DNA was negative, and Gram’s staining revealed no organisms. Antimicrobial therapy was discontinued, and the patient was discharged home.

There was also a history of coronavirus disease 2019, which had been diagnosed 16 months before this presentation. Current medications included golimumab, apixaban, prednisone, and trimethoprim–sulfamethoxazole. There were no known allergies. The patient lived with his wife and four children. He had previously worked in construction; he had been released from prison 3 months before this presentation and was not currently working. He had a remote history of smoking tobacco; he did not drink alcohol or use illicit drugs. His grandmother had hypertension.

On examination in the emergency department, the patient was somnolent but arose in response to verbal stimuli. His level of alertness fluctuated, he was only intermittently able to answer simple questions, and he could not provide a coherent history of his illness. The temperature was 39.5°C, the blood pressure 122/71 mm Hg, the heart rate 81 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 96% while he was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 29.7. He was oriented to person and place but not to time. There was no neck stiffness. Mild injection in the left eye was present, but there were no oral or skin lesions. The patient was not able to participate fully in a neurologic examination, but he was able to move his arms and legs; no focal neurologic findings were noted on observation. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Blood levels of glucose and electrolytes were normal, as were results of liver-function, kidney-function, and coagulation tests. Other laboratory test results are shown in Table 1. Urinalysis revealed trace ketones but was otherwise normal. The blood acetaminophen level was less than 5.0 μg per milliliter (reference range, 0.0 to 25.0); blood testing for ethanol was negative. Testing of a nasopharyngeal swab specimen for respiratory viral pathogens was positive for human rhinovirus or enterovirus. Blood specimens were obtained for culture. Imaging studies were obtained.

Dr. Pamela W. Schaefer: A chest radiograph was normal. Computed tomography (CT) of the head revealed mucosal thickening with layering fluid levels in both maxillary sinuses, but the study was otherwise normal. CT angiography of the head and neck, performed with and without the administration of intravenous contrast material, revealed normal arterial and venous vasculature.

Dr. Suarez: Treatment with vancomycin, ceftriaxone, ampicillin, and acyclovir was initiated. The patient was admitted to the hospital. Treatment with apixaban was stopped and heparin administered intravenously in anticipation of performing a lumbar puncture. Fever and headache abated, but the patient’s mental status did not improve. Blood cultures showed no growth. On the fourth hospital day, a lumbar puncture was performed. The opening pressure was not obtained. CSF analysis revealed a normal total protein level, a glucose level of 40 mg per deciliter (2.2 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]), a red-cell count of 2 per microliter (reference range, 0 to 5), and a nucleated-cell count of 284 per microliter (reference range, 0 to 5), with 72% lymphocytes, 13% neutrophils, 11% monocytes, and 4% unclassified cells. Nucleic acid amplification testing for herpes simplex virus type 1 and type 2 DNA was negative, and Gram’s staining revealed no organisms. No acid-fast bacilli were observed on a mycobacterial smear, and no fungi were seen on examination of a fungal wet preparation. Testing of the CSF for cryptococcal antigen and enterovirus RNA was negative.

Additional diagnostic testing was performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Neuro-Behcet's disease\n\nThe patient's history of Behcet's disease, combined with new neurological symptoms such as confusion, headache, and neck stiffness, suggest a neurological manifestation of his existing condition. The patient's CSF analysis shows lymphocytic predominance, which is consistent with Neuro-Behcet's disease. The absence of organisms in the CSF and the negative results for herpes simplex virus and enterovirus RNA rule out infectious causes. The patient's symptoms did not improve with antibiotic treatment, further suggesting a non-infectious cause. Therefore, the most likely diagnosis is Neuro-Behcet's disease.""
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        ""content"": ""Neuro-Behcet's disease\n\nThe patient's history of Behcet's disease, along with new onset confusion, headache, and fever, suggest a neurological manifestation of his underlying condition. Behcet's disease is a rare, chronic, systemic vasculitis that can affect multiple organ systems, including the nervous system. Neurological involvement, known as Neuro-Behcet's disease, can present with a variety of symptoms, including headache, confusion, and fever, as seen in this patient. The patient's lumbar puncture results, showing lymphocytic predominance, are consistent with Neuro-Behcet's disease. The absence of organisms on Gram stain and negative viral testing make an infectious cause of his symptoms less likely.""
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        ""content"": ""The patient is a 32-year-old male with a history of Beh\u00e7et\u2019s disease presenting with confusion, headache, neck stiffness, and fever. The differential diagnosis for this patient includes meningitis, encephalitis, cerebral vasculitis, and neuro-Beh\u00e7et\u2019s disease. The patient's history of lymphocyte-predominant meningitis and current symptoms of confusion, headache, neck stiffness, and fever suggest a central nervous system infection such as meningitis or encephalitis. However, the patient's CSF analysis shows a lymphocytic predominance and negative testing for common infectious causes of meningitis and encephalitis, making these diagnoses less likely. Cerebral vasculitis could also present with similar symptoms, but the patient's CT angiography of the head and neck was normal, making this diagnosis less likely. Neuro-Beh\u00e7et\u2019s disease, a rare neurological complication of Beh\u00e7et\u2019s disease, can present with a variety of neurological symptoms including confusion and headache. Given the patient's history of Beh\u00e7et\u2019s disease, his neurological symptoms, and the lymphocytic predominance on CSF analysis, neuro-Beh\u00e7et\u2019s disease is the most likely diagnosis.\n\nDiagnosis: Neuro-Beh\u00e7et\u2019s disease.""
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10.1056/NEJMcpc2201247,Case 26-2022: A 48-Year-Old Woman with Cystic Lung Disease,"Hemoglobin (g/dl)	11.0–16.0	12.9	 	11.5
Hematocrit (%)	34.0–45.0	38.5	 	35.1
Platelet count (per μl)	 	413,000	 	390,000
White-cell count (per μl)	 	12,800	 	11,560
Differential count (per μl)				
Neutrophils	1500–7800	10,200	 	7660
Lymphocytes	 	1400	 	2570
Monocytes	 00	1000	 	1070
Eosinophils	 	100	 	150
Total protein (g/dl)	6.4–8.3	6.7	6. .3	6.4
Albumin (g/dl)	4. 	3.6	 	3.3
Alkaline phosphatase (U/liter)	35–104	131	 	99
Aspartate aminotransferase (U/liter)	15–41	38	 	24
Alanine aminotransferase (U/liter)	14–54	60	 	26
Total bilirubin (mg/dl)†	<1.2	0.3	0.0–1.0	0.1
International normalized ratio	 	1.0	—	—
Thyrotropin (μIU/ml)	—	—	0.4 0	0.74",Langerhans-cell histiocytosis of the lung and liver.,Langerhans-cell histiocytosis of the lung and liver.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old woman was admitted to this hospital because of multiple lung and liver lesions identified during an evaluation for abdominal pain.

The patient had been in her usual state of health until 10 days before this admission, when burning epigastric pain developed after she ate a meal. Nausea and vomiting occurred 1 hour later; there was no diarrhea. After the pain persisted for 8 hours, she presented to the emergency department of another hospital for evaluation.

Table 1.

Laboratory Data.
On examination, the temperature was 36.8°C, the blood pressure 136/94 mm Hg, the pulse 80 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.8. The abdomen was soft but distended; there was diffuse mild tenderness on palpation, without rebound or guarding. The white-cell count was 12,800 per microliter (reference range, 4500 to 11,000) and the blood lipase level 147 U per liter (reference range, 13 to 60); other laboratory test results are shown in Table 1. The pain did not resolve after treatment with intravenous famotidine and oral simethicone. Imaging studies were obtained.

Dr. Melissa C. Price: A chest radiograph showed faint nodular opacities in the lungs, predominantly in the upper lobes. Computed tomography (CT) of the abdomen, performed after the administration of intravenous contrast material, revealed multiple fluid-filled small-bowel loops with associated mild mesenteric edema and trace ascites. There was no biliary dilatation. In addition, there were numerous hypoattenuating hepatic lesions with peripheral enhancement.

Dr. Gumuser: The patient was admitted to the other hospital with a diagnosis of possible small-bowel obstruction and pneumonia. Treatment with intravenous fluids and ceftriaxone, oral doxycycline, and bowel rest was initiated. On the second hospital day, additional imaging studies of the liver were obtained.

Figure 1.

Imaging Studies.
Dr. Price: Magnetic resonance imaging (MRI) of the abdomen (Figure 1), performed with and without the administration of intravenous contrast material, revealed bilobar hepatic lesions with peripheral enhancement, high T2 signal, and diffusion restriction.

Dr. Gumuser: Blood was obtained for microbiologic culture, and treatment with intravenous metronidazole was initiated. On the third hospital day, the abdominal pain had resolved, and the patient began drinking clear fluids. On the fourth hospital day, ultrasound-guided liver biopsy was performed. While the results of the liver biopsy were pending, the patient resumed a normal diet, with no recurrence of abdominal pain. Treatment with oral doxycycline and intravenous ceftriaxone and metronidazole was continued.

Dr. Price: On the sixth hospital day, CT of the chest (Figure 1), performed without the administration of intravenous contrast material, revealed numerous irregular cysts and cavitary nodules in the lungs, which were most pronounced in the upper lobes, as well as solid and subsolid parenchymal nodules that measured less than 1.0 cm in diameter. There were multiple nodules in the thyroid gland, measuring up to 2.8 cm in diameter in the inferior left thyroid lobe. There was a 1.7-cm nodule with soft-tissue attenuation in the right breast.

Dr. Gumuser: On the eighth hospital day, bronchoscopy was performed. The airways were inspected to the segmental level, and no abnormalities were visualized. Transbronchial biopsy and bronchoalveolar lavage (BAL) were performed in the right upper lobe. Examination of the BAL fluid revealed 321 white cells per microliter (reference range, 94 to 175). Gram’s staining and examination of an acid-fast bacilli smear of the BAL fluid were negative.

On the ninth hospital day, results of the liver biopsy became available, showing extensive eosinophilic infiltration of the liver parenchyma with associated moderate steatosis. Staining of the biopsy specimen for microorganisms, including mycobacteria, was negative. Cultures of blood obtained on the second hospital day showed no growth. The patient was transferred to this hospital for further care.

On arrival, the patient reported a mild sore throat that had developed after bronchoscopy, but there was no abdominal pain. She had lost 2 kg of weight before the hospitalization, in the context of dietary changes. She had no history of fever but reported a several-year history of mild shortness of breath with walking that she attributed to smoking. Her surgical history included cholecystectomy and cesarean section. Results of a Papanicolaou test performed 3 months before this presentation had been normal; the patient had not undergone mammography or colonoscopy. She took no medications and had no known drug allergies.

The patient lived in an urban area of New England. She was born in Portugal and had immigrated to the United States 40 years earlier. She had not traveled recently; her last trip had been to Portugal 25 years before this admission. The patient was divorced, lived alone, and worked in a medical laboratory. She had no known exposure to chemicals or dust; a coworker at a previous office job had had an atypical infection attributed to mold in the workplace. She had smoked one pack of cigarettes per day for the past 30 years. She drank alcohol three times a week and did not use illicit drugs. Her mother had died from colon cancer at 43 years of age.

On examination, the temperature was 36.2°C, the blood pressure 130/64 mm Hg, the pulse 65 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The physical examination was normal.

A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old woman was admitted to this hospital because of multiple lung and liver lesions identified during an evaluation for abdominal pain.

The patient had been in her usual state of health until 10 days before this admission, when burning epigastric pain developed after she ate a meal. Nausea and vomiting occurred 1 hour later; there was no diarrhea. After the pain persisted for 8 hours, she presented to the emergency department of another hospital for evaluation.

Table 1.

Laboratory Data.
On examination, the temperature was 36.8°C, the blood pressure 136/94 mm Hg, the pulse 80 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.8. The abdomen was soft but distended; there was diffuse mild tenderness on palpation, without rebound or guarding. The white-cell count was 12,800 per microliter (reference range, 4500 to 11,000) and the blood lipase level 147 U per liter (reference range, 13 to 60); other laboratory test results are shown in Table 1. The pain did not resolve after treatment with intravenous famotidine and oral simethicone. Imaging studies were obtained.

Dr. Melissa C. Price: A chest radiograph showed faint nodular opacities in the lungs, predominantly in the upper lobes. Computed tomography (CT) of the abdomen, performed after the administration of intravenous contrast material, revealed multiple fluid-filled small-bowel loops with associated mild mesenteric edema and trace ascites. There was no biliary dilatation. In addition, there were numerous hypoattenuating hepatic lesions with peripheral enhancement.

Dr. Gumuser: The patient was admitted to the other hospital with a diagnosis of possible small-bowel obstruction and pneumonia. Treatment with intravenous fluids and ceftriaxone, oral doxycycline, and bowel rest was initiated. On the second hospital day, additional imaging studies of the liver were obtained.

Figure 1.

Imaging Studies.
Dr. Price: Magnetic resonance imaging (MRI) of the abdomen (Figure 1), performed with and without the administration of intravenous contrast material, revealed bilobar hepatic lesions with peripheral enhancement, high T2 signal, and diffusion restriction.

Dr. Gumuser: Blood was obtained for microbiologic culture, and treatment with intravenous metronidazole was initiated. On the third hospital day, the abdominal pain had resolved, and the patient began drinking clear fluids. On the fourth hospital day, ultrasound-guided liver biopsy was performed. While the results of the liver biopsy were pending, the patient resumed a normal diet, with no recurrence of abdominal pain. Treatment with oral doxycycline and intravenous ceftriaxone and metronidazole was continued.

Dr. Price: On the sixth hospital day, CT of the chest (Figure 1), performed without the administration of intravenous contrast material, revealed numerous irregular cysts and cavitary nodules in the lungs, which were most pronounced in the upper lobes, as well as solid and subsolid parenchymal nodules that measured less than 1.0 cm in diameter. There were multiple nodules in the thyroid gland, measuring up to 2.8 cm in diameter in the inferior left thyroid lobe. There was a 1.7-cm nodule with soft-tissue attenuation in the right breast.

Dr. Gumuser: On the eighth hospital day, bronchoscopy was performed. The airways were inspected to the segmental level, and no abnormalities were visualized. Transbronchial biopsy and bronchoalveolar lavage (BAL) were performed in the right upper lobe. Examination of the BAL fluid revealed 321 white cells per microliter (reference range, 94 to 175). Gram’s staining and examination of an acid-fast bacilli smear of the BAL fluid were negative.

On the ninth hospital day, results of the liver biopsy became available, showing extensive eosinophilic infiltration of the liver parenchyma with associated moderate steatosis. Staining of the biopsy specimen for microorganisms, including mycobacteria, was negative. Cultures of blood obtained on the second hospital day showed no growth. The patient was transferred to this hospital for further care.

On arrival, the patient reported a mild sore throat that had developed after bronchoscopy, but there was no abdominal pain. She had lost 2 kg of weight before the hospitalization, in the context of dietary changes. She had no history of fever but reported a several-year history of mild shortness of breath with walking that she attributed to smoking. Her surgical history included cholecystectomy and cesarean section. Results of a Papanicolaou test performed 3 months before this presentation had been normal; the patient had not undergone mammography or colonoscopy. She took no medications and had no known drug allergies.

The patient lived in an urban area of New England. She was born in Portugal and had immigrated to the United States 40 years earlier. She had not traveled recently; her last trip had been to Portugal 25 years before this admission. The patient was divorced, lived alone, and worked in a medical laboratory. She had no known exposure to chemicals or dust; a coworker at a previous office job had had an atypical infection attributed to mold in the workplace. She had smoked one pack of cigarettes per day for the past 30 years. She drank alcohol three times a week and did not use illicit drugs. Her mother had died from colon cancer at 43 years of age.

On examination, the temperature was 36.2°C, the blood pressure 130/64 mm Hg, the pulse 65 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The physical examination was normal.

A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with multiple lung and liver lesions, abdominal pain, and a history of smoking. The liver biopsy showed extensive eosinophilic infiltration of the liver parenchyma with associated moderate steatosis. The patient's history of smoking, the presence of lung and liver lesions, and the eosinophilic infiltration of the liver suggest a diagnosis of Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly known as Churg-Strauss syndrome. This is a rare autoimmune condition characterized by asthma, high levels of eosinophils, and inflammation of small to medium-sized blood vessels. The patient's symptoms and the results of the liver biopsy are consistent with this diagnosis. \n\nDiagnosis: Eosinophilic Granulomatosis with Polyangiitis (EGPA)""
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        ""content"": ""The patient presents with multiple lung and liver lesions, abdominal pain, and a history of smoking. The liver biopsy showed extensive eosinophilic infiltration of the liver parenchyma with associated moderate steatosis. The patient's history of smoking, the presence of lung and liver lesions, and the eosinophilic infiltration of the liver suggest a parasitic infection, possibly Echinococcus. Echinococcosis is a parasitic disease caused by infection with tiny tapeworms of the genus Echinococcus. The disease occurs in two main forms: cystic echinococcosis (also known as hydatid disease) and alveolar echinococcosis. Both forms of the disease are characterized by slow-growing, cyst-like masses or lesions in the body, often in the liver and lungs. The patient's history of immigration from Portugal, a country where Echinococcus is endemic, further supports this diagnosis.\n\nDiagnosis: Echinococcosis (Hydatid disease)""
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        ""content"": ""The patient is a 48-year-old woman presenting with multiple lung and liver lesions, abdominal pain, nausea, and vomiting. The differential diagnosis for this patient includes metastatic cancer, infectious diseases such as tuberculosis or fungal infections, and autoimmune diseases such as sarcoidosis or granulomatosis with polyangiitis. The patient's history of smoking and family history of colon cancer increases her risk for malignancy. However, the liver biopsy showed extensive eosinophilic infiltration of the liver parenchyma with associated moderate steatosis, which is not typical for metastatic cancer. The patient's lack of recent travel and negative cultures make an infectious cause less likely. The patient's symptoms and imaging findings are consistent with an autoimmune process, but the lack of other systemic symptoms makes this less likely. The patient's history of smoking, the presence of lung and liver lesions, and the eosinophilic infiltration seen on liver biopsy are all consistent with a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome. This is a rare autoimmune condition characterized by asthma, sinusitis, and eosinophilia, and can affect various organs including the lungs and liver. \n\nDiagnosis: Eosinophilic granulomatosis with polyangiitis (EGPA) or Churg-Strauss syndrome.""
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10.1056/NEJMcpc2201241,Case 25-2022: A 25-Year-Old Woman with Headache and Blurred Vision,"Human immunodeficiency virus type 1 and 2 antibodies	Nonreactive	Nonreactive
Treponemal antibody	Nonreactive	Nonreactive
1,3-β-d-glucan (pg/ml)	<60	39
Galactomannan antigen index	 9	0.07
Cryptococcal antigen	Negative	Negative
T-SPOT.TB interferon-γ release assay	Negative	Negative
Toxoplasma IgG	Negative	Negative
Herpes simplex virus type 1 and 2 antibodies	Negative	Negative
Lyme IgG and IgM	Negative	Negative
Brucella IgG and IgM	Negative	Negative
Angiotensin-converting enzyme (U/liter)	16–85	11
Urine		
Histoplasma antigen	Negative	Negative
Coccidioides antigen	Negative	Negative
Blastomyces antigen	Not detected	Not detected",Chronic Candida albicans meningitis.,Candida meningitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 25-year-old woman with a history of migraines was admitted to this hospital with progressively worsening headaches and photophobia during the previous 6 weeks and a 1-week history of nausea, vomiting, and blurred vision.

Six weeks before this admission, the patient began to have headaches that were not characteristic of her previous migraines. She described these headaches as discomfort in the middle of her head that was associated with photophobia, phonophobia, and tinnitus. She reported that she was occasionally awakened from sleep because of headache and that the headache was always present on awakening in the morning. The headache was worse with coughing and abated with standing; treatment with ibuprofen did not reduce the discomfort.

Figure 1.

Imaging Studies of the Head and Spine.
One week before admission, nausea and vomiting developed, along with blurred vision when the patient looked to the left. She also reported occasional episodes of total vision loss that lasted for several seconds. When she was unable to eat food because of worsening nausea and vomiting, she presented to another hospital for evaluation. Computed tomography (CT) of the head revealed dilatation of the lateral and third ventricles with hypodensity that involved the dorsal brain stem and cerebellar hemispheres (Figure 1A); a possible soft-tissue mass in the region of the fourth ventricular outlet was also observed. The patient was transferred to the emergency department of this hospital for further evaluation.

On arrival, the patient reported ongoing headache and nausea. Other medical history included obesity and opioid use disorder, which was treated with oral buprenorphine–naloxone and was complicated by relapses with injection of heroin; she last injected heroin 1 month before admission. Other medications included ibuprofen as needed. She had no known allergies. She smoked a half pack of cigarettes daily and did not drink alcohol. The patient lived in a wooded area of New England with four cats and one dog. She spent time outside, although she had become less active owing to headache. She was sexually active with one male partner and had no history of sexually transmitted infections. She had not traveled outside of New England. She had had periods of homelessness in the past, but she had not stayed in shelters. She had been incarcerated 2 years before this admission. She did not eat uncooked meat or seafood. Two paternal family members had had ovarian cancer.

Laboratory Data.
On examination, the patient was alert, interactive, and did not appear to be in distress. The temperature was 36.9°C, the blood pressure 117/58 mm Hg, the heart rate 77 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while she was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 42.6. There were track marks on the legs. The patient was oriented to time, place, and person. Speech was fluent with intact naming, repetition, and comprehension. On bedside visual field testing, she reported decreased vision in the peripheral fields and double vision on looking to the far left, which was accompanied by a left sixth-nerve palsy; papilledema was present in both eyes. The remainder of the cranial-nerve examination was normal. Tests of motor strength and sensation were normal. Blood levels of glucose and electrolytes were normal, as were the complete blood count and differential count and the results of liver- and kidney-function tests; other laboratory test results are shown in Table 1. Imaging studies were obtained.

Dr. Saurabh Rohatgi: Magnetic resonance imaging (MRI) of the head was performed after the administration of intravenous contrast material. T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging showed elevated signal hyperintensity involving the periaqueductal gray matter, dorsal midbrain, dorsal pons, superior and middle cerebellar peduncles, dentate nuclei, and cerebellar white matter (Figure 1B). There was obstructive hydrocephalus with transependymal flow of cerebrospinal fluid (CSF). Leptomeningeal enhancement was observed surrounding the brain stem and extending through the inferior aspect of the posterior fossa with entrapment of the fourth ventricle (Figure 1C). There was also leptomeningeal enhancement along multiple upper and lower cranial nerves.

Dr. Clark: Treatment with intravenous acetazolamide and oral dexamethasone was initiated, and the patient was admitted to the neurocritical care unit. On the first hospital day, the patient underwent stereotactically guided endoscopic exploration of the right ventricle. The right foramen of Monro was patent, but there was obstruction in the underlying third ventricle due to adhesions and aberrant anatomical features that precluded endoscopic third ventriculostomy. An external ventricular drain was placed; the opening pressure was 10 cm of water. Analysis of a CSF specimen obtained from the external ventricular drain showed 2 white cells per microliter (reference range, 0 to 5), of which 90% were neutrophils and 10% were monocytes, and 768 red cells per microliter (reference value, 0); the CSF levels of protein and glucose were normal.

Dexamethasone therapy was discontinued, and treatment with intravenous vancomycin and ceftriaxone was initiated. Airborne precautions were instituted, and an induced sputum sample was obtained for mycobacterial culture. No acid-fast bacilli were observed on examination of smears of three sputum samples obtained sequentially, and polymerase-chain-reaction (PCR) testing of one of the samples for Mycobacterium tuberculosis was negative. CSF cultures were negative, and cytologic examination of the CSF did not show malignant cells.

Dr. Rohatgi: On the third hospital day, CT of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, was normal. On the fourth hospital day, MRI of the spine revealed diffuse leptomeningeal enhancement, most notably in the lumbar spine, with masslike confluent enhancement filling the subarachnoid space at L5–S2 (Figure 1F).

Dr. Clark: On the fifth hospital day, a lumbar puncture was performed; the CSF analysis revealed 1120 nucleated cells, of which 77% were neutrophils, and 23 red cells. The CSF protein level was 740 mg per deciliter (reference range, 5 to 55) and the glucose level 19 mg per deciliter (1.1 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]). The opening pressure was 10 cm of water relative to the external auditory meatus, which was the same as the pressure that was simultaneously recorded from the clamped external ventricular drain. CSF was sent for culture and cytologic studies.

A diagnostic test result was received.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 25-year-old woman with a history of migraines was admitted to this hospital with progressively worsening headaches and photophobia during the previous 6 weeks and a 1-week history of nausea, vomiting, and blurred vision.

Six weeks before this admission, the patient began to have headaches that were not characteristic of her previous migraines. She described these headaches as discomfort in the middle of her head that was associated with photophobia, phonophobia, and tinnitus. She reported that she was occasionally awakened from sleep because of headache and that the headache was always present on awakening in the morning. The headache was worse with coughing and abated with standing; treatment with ibuprofen did not reduce the discomfort.

Figure 1.

Imaging Studies of the Head and Spine.
One week before admission, nausea and vomiting developed, along with blurred vision when the patient looked to the left. She also reported occasional episodes of total vision loss that lasted for several seconds. When she was unable to eat food because of worsening nausea and vomiting, she presented to another hospital for evaluation. Computed tomography (CT) of the head revealed dilatation of the lateral and third ventricles with hypodensity that involved the dorsal brain stem and cerebellar hemispheres (Figure 1A); a possible soft-tissue mass in the region of the fourth ventricular outlet was also observed. The patient was transferred to the emergency department of this hospital for further evaluation.

On arrival, the patient reported ongoing headache and nausea. Other medical history included obesity and opioid use disorder, which was treated with oral buprenorphine–naloxone and was complicated by relapses with injection of heroin; she last injected heroin 1 month before admission. Other medications included ibuprofen as needed. She had no known allergies. She smoked a half pack of cigarettes daily and did not drink alcohol. The patient lived in a wooded area of New England with four cats and one dog. She spent time outside, although she had become less active owing to headache. She was sexually active with one male partner and had no history of sexually transmitted infections. She had not traveled outside of New England. She had had periods of homelessness in the past, but she had not stayed in shelters. She had been incarcerated 2 years before this admission. She did not eat uncooked meat or seafood. Two paternal family members had had ovarian cancer.

Laboratory Data.
On examination, the patient was alert, interactive, and did not appear to be in distress. The temperature was 36.9°C, the blood pressure 117/58 mm Hg, the heart rate 77 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while she was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 42.6. There were track marks on the legs. The patient was oriented to time, place, and person. Speech was fluent with intact naming, repetition, and comprehension. On bedside visual field testing, she reported decreased vision in the peripheral fields and double vision on looking to the far left, which was accompanied by a left sixth-nerve palsy; papilledema was present in both eyes. The remainder of the cranial-nerve examination was normal. Tests of motor strength and sensation were normal. Blood levels of glucose and electrolytes were normal, as were the complete blood count and differential count and the results of liver- and kidney-function tests; other laboratory test results are shown in Table 1. Imaging studies were obtained.

Dr. Saurabh Rohatgi: Magnetic resonance imaging (MRI) of the head was performed after the administration of intravenous contrast material. T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging showed elevated signal hyperintensity involving the periaqueductal gray matter, dorsal midbrain, dorsal pons, superior and middle cerebellar peduncles, dentate nuclei, and cerebellar white matter (Figure 1B). There was obstructive hydrocephalus with transependymal flow of cerebrospinal fluid (CSF). Leptomeningeal enhancement was observed surrounding the brain stem and extending through the inferior aspect of the posterior fossa with entrapment of the fourth ventricle (Figure 1C). There was also leptomeningeal enhancement along multiple upper and lower cranial nerves.

Dr. Clark: Treatment with intravenous acetazolamide and oral dexamethasone was initiated, and the patient was admitted to the neurocritical care unit. On the first hospital day, the patient underwent stereotactically guided endoscopic exploration of the right ventricle. The right foramen of Monro was patent, but there was obstruction in the underlying third ventricle due to adhesions and aberrant anatomical features that precluded endoscopic third ventriculostomy. An external ventricular drain was placed; the opening pressure was 10 cm of water. Analysis of a CSF specimen obtained from the external ventricular drain showed 2 white cells per microliter (reference range, 0 to 5), of which 90% were neutrophils and 10% were monocytes, and 768 red cells per microliter (reference value, 0); the CSF levels of protein and glucose were normal.

Dexamethasone therapy was discontinued, and treatment with intravenous vancomycin and ceftriaxone was initiated. Airborne precautions were instituted, and an induced sputum sample was obtained for mycobacterial culture. No acid-fast bacilli were observed on examination of smears of three sputum samples obtained sequentially, and polymerase-chain-reaction (PCR) testing of one of the samples for Mycobacterium tuberculosis was negative. CSF cultures were negative, and cytologic examination of the CSF did not show malignant cells.

Dr. Rohatgi: On the third hospital day, CT of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, was normal. On the fourth hospital day, MRI of the spine revealed diffuse leptomeningeal enhancement, most notably in the lumbar spine, with masslike confluent enhancement filling the subarachnoid space at L5–S2 (Figure 1F).

Dr. Clark: On the fifth hospital day, a lumbar puncture was performed; the CSF analysis revealed 1120 nucleated cells, of which 77% were neutrophils, and 23 red cells. The CSF protein level was 740 mg per deciliter (reference range, 5 to 55) and the glucose level 19 mg per deciliter (1.1 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]). The opening pressure was 10 cm of water relative to the external auditory meatus, which was the same as the pressure that was simultaneously recorded from the clamped external ventricular drain. CSF was sent for culture and cytologic studies.

A diagnostic test result was received.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Cryptococcal meningitis\n\nThe patient's symptoms of headache, photophobia, nausea, vomiting, and blurred vision are consistent with increased intracranial pressure. The MRI findings of leptomeningeal enhancement and obstructive hydrocephalus further support this. The patient's history of opioid use disorder and periods of homelessness suggest a higher risk for infectious diseases, including those that can cause meningitis. The CSF analysis showing a high protein level and low glucose level is typical of bacterial or fungal meningitis. Given the patient's risk factors and the negative results for bacterial cultures and tuberculosis testing, a fungal cause such as Cryptococcus is likely. Cryptococcus is a yeast that can cause meningitis, particularly in individuals with compromised immune systems. It is often found in soil and bird droppings and can be inhaled into the lungs, where it can spread to other parts of the body, including the brain and spinal cord.""
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        ""content"": ""The patient's symptoms of headache, photophobia, nausea, vomiting, and blurred vision, along with the findings of papilledema and hydrocephalus on imaging, suggest increased intracranial pressure. The MRI findings of leptomeningeal enhancement and masslike confluent enhancement in the lumbar spine suggest a process involving the meninges. The CSF analysis showing elevated protein and a predominance of neutrophils is suggestive of an infectious or inflammatory process. Given the patient's history of opioid use disorder with injection drug use, one possibility is an infection such as bacterial meningitis. However, the negative cultures and lack of response to antibiotics argue against this. Another possibility given the patient's history and the imaging findings is a neoplastic process such as leptomeningeal carcinomatosis, but the lack of malignant cells on CSF cytology argues against this. The patient's history of living in a wooded area of New England raises the possibility of a tick-borne illness such as Lyme disease, which can cause meningitis and cranial neuropathies. \n\nDiagnosis: Lyme disease.""
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        ""content"": ""The patient is a young woman with a history of migraines who presents with progressively worsening headaches, photophobia, nausea, vomiting, and blurred vision. The headaches are not characteristic of her previous migraines and are worse with coughing and better with standing. She also has occasional episodes of total vision loss. The patient has a history of obesity and opioid use disorder. The differential diagnosis for this patient includes intracranial hypertension, meningitis, brain tumor, and brain abscess. The patient's headaches are worse with coughing and better with standing, which is characteristic of intracranial hypertension. However, her MRI shows elevated signal hyperintensity involving the periaqueductal gray matter, dorsal midbrain, dorsal pons, superior and middle cerebellar peduncles, dentate nuclei, and cerebellar white matter, as well as obstructive hydrocephalus and leptomeningeal enhancement. These findings are more suggestive of a mass or infectious process. The patient's history of opioid use disorder and injection of heroin raises the possibility of an infectious process such as meningitis or a brain abscess. However, her CSF analysis shows only 2 white cells per microliter and normal levels of protein and glucose, which is not typical of meningitis or a brain abscess. The patient's symptoms and imaging findings are most consistent with a brain tumor. However, the patient's CSF cytology did not show malignant cells, which makes a brain tumor less likely. The patient's symptoms, imaging findings, and CSF analysis are most consistent with a diagnosis of intracranial hypertension.\n\nDiagnosis: Intracranial hypertension.""
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10.1056/NEJMcpc2201244,"Case 24-2022: A 31-Year-Old Man with Perianal and Penile Ulcers, Rectal Pain, and Rash",,"Infection with monkeypox virus, West African clade.",nfection with monkeypox virus.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 31-year-old man was admitted to 
this hospital because of perianal and penile ulcers, rectal pain, and vesiculopustular rash. The patient had been in his usual state of health until 9 days before this admission, when he noticed several itchy white “bumps” around the anus that subsequently evolved into ulcerative lesions. The next day, he sought evaluation at a primary care clinic of another hospital. Tests for human immunodeficiency virus (HIV), syphilis, gonorrhea, and chlamydia were performed. An injection of penicillin G benzathine was administered, and treatment with valacyclovir was started.
During the next 5 days, the perianal ulcers did not abate, and the patient stopped taking valacyclovir. Painful proctitis with rectal bleeding and malodorous, mucopurulent discharge developed, along with fever, chills, drenching sweats, and new tender swelling in the groin. Three days before this admission, a new painless ulcer appeared on the penis that was similar in appearance to the perianal ulcers. Two days before this admission, new scattered vesicular lesions appeared on the arms and legs, and the patient presented to the infectious disease clinic of this hospital for evaluation.
Additional history was obtained from the patient. Fourteen years before this evaluation, sore throat and upper body rash developed; he received a diagnosis of secondary syphilis and was treated with penicillin G benzathine. He also had a history of recurrent oral herpes simplex virus (HSV) infection, for which he was treated intermittently with valacyclovir. He took daily oral emtricitabine and tenofovir for HIV preexposure prophylaxis (PrEP). There were no known drug allergies. The patient lived in a suburban area of Massachusetts with two roommates and a cat. Two weeks before this evaluation, he had traveled to an urban area of southeastern Canada. During this trip, he had had sex with male partners without the use of barrier protection. There was no other recent travel. The patient did not smoke cigarettes or use illicit drugs; he drank alcohol rarely. On examination, the temperature was 36.5°C,  the blood pressure 130/86 mm Hg, the pulse 75  beats per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 23.9. There were six tender perianal ulcers, measuring less than 1 cm in diameter, with raised, firm margins. There was also one ulcer on the dorsum of the penile shaft, measuring 7 mm in diameter, with raised borders (Fig. 1). Painful bilateral inguinal lymphadenopathy was present. The perianal skin was weeping, and there was proctitis with severe tenderness that precluded digital rectal examination. In addition, there were approximately 12 papulovesicular lesions scattered across the chest, back, arms, and legs. The lesions measured 2 mm in diameter, were filled with clear fluid, and had surrounding erythema (Fig. 2A and 2B). Blood levels of electrolytes and glucose were normal, as were the results of kidney-function and liver-function tests. A blood test for treponemal antibodies was positive; a rapid plasma reagin (RPR) test was reactive at a dilution of 1:1. A blood test for HIV was nonreactive, and tests of urine and rectal specimens for Neisseria gonorrhoeae and Chlamydia trachomatis nucleic acids were negative. A test of a specimen obtained from a perianal ulcer for HSV nucleic acids was performed, and a blood sample was obtained for bacterial culture. An injection of ceftriaxone was administered, and treatment with valacyclovir and doxycycline was started.During the next 2 days, the ulcers did not abate and the rectal pain worsened, such that the patient was not able to sit, sleep, or have bowel movements. Additional skin lesions appeared. The patient returned to the infectious disease clinic for evaluation. Anoscopy revealed intense rectal and anal inflammation with shallow ulcerations and purulent exudate, findings consistent with proctitis (Fig. 3). The patient was admitted to this hospital.
On examination, the patient appeared uncomfortable because of rectal pain. Skin lesions that had become pustular with an erythematous 
base were scattered across the scalp, chest, back, legs, and arms, including one on the palm (Fig. 2C). There were no lesions in the mouth. 
Multiple tender, enlarged inguinal lymph nodes, measuring more than 1 cm in diameter, were present. The perianal and penile ulcers were tender and had heaped margins around a central dry base. The complete blood count and the white-cell differential count were normal. Swabs from a perianal ulcer and a chest skin lesion were obtained for bacterial culture.Treatment with intravenous acyclovir was 
started, and doxycycline was continued; stool softeners and hydromorphone were administered. A blood test for HIV type 1 RNA was 
performed. A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 31-year-old man was admitted to 
this hospital because of perianal and penile ulcers, rectal pain, and vesiculopustular rash. The patient had been in his usual state of health until 9 days before this admission, when he noticed several itchy white “bumps” around the anus that subsequently evolved into ulcerative lesions. The next day, he sought evaluation at a primary care clinic of another hospital. Tests for human immunodeficiency virus (HIV), syphilis, gonorrhea, and chlamydia were performed. An injection of penicillin G benzathine was administered, and treatment with valacyclovir was started.
During the next 5 days, the perianal ulcers did not abate, and the patient stopped taking valacyclovir. Painful proctitis with rectal bleeding and malodorous, mucopurulent discharge developed, along with fever, chills, drenching sweats, and new tender swelling in the groin. Three days before this admission, a new painless ulcer appeared on the penis that was similar in appearance to the perianal ulcers. Two days before this admission, new scattered vesicular lesions appeared on the arms and legs, and the patient presented to the infectious disease clinic of this hospital for evaluation.
Additional history was obtained from the patient. Fourteen years before this evaluation, sore throat and upper body rash developed; he received a diagnosis of secondary syphilis and was treated with penicillin G benzathine. He also had a history of recurrent oral herpes simplex virus (HSV) infection, for which he was treated intermittently with valacyclovir. He took daily oral emtricitabine and tenofovir for HIV preexposure prophylaxis (PrEP). There were no known drug allergies. The patient lived in a suburban area of Massachusetts with two roommates and a cat. Two weeks before this evaluation, he had traveled to an urban area of southeastern Canada. During this trip, he had had sex with male partners without the use of barrier protection. There was no other recent travel. The patient did not smoke cigarettes or use illicit drugs; he drank alcohol rarely. On examination, the temperature was 36.5°C,  the blood pressure 130/86 mm Hg, the pulse 75  beats per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 23.9. There were six tender perianal ulcers, measuring less than 1 cm in diameter, with raised, firm margins. There was also one ulcer on the dorsum of the penile shaft, measuring 7 mm in diameter, with raised borders (Fig. 1). Painful bilateral inguinal lymphadenopathy was present. The perianal skin was weeping, and there was proctitis with severe tenderness that precluded digital rectal examination. In addition, there were approximately 12 papulovesicular lesions scattered across the chest, back, arms, and legs. The lesions measured 2 mm in diameter, were filled with clear fluid, and had surrounding erythema (Fig. 2A and 2B). Blood levels of electrolytes and glucose were normal, as were the results of kidney-function and liver-function tests. A blood test for treponemal antibodies was positive; a rapid plasma reagin (RPR) test was reactive at a dilution of 1:1. A blood test for HIV was nonreactive, and tests of urine and rectal specimens for Neisseria gonorrhoeae and Chlamydia trachomatis nucleic acids were negative. A test of a specimen obtained from a perianal ulcer for HSV nucleic acids was performed, and a blood sample was obtained for bacterial culture. An injection of ceftriaxone was administered, and treatment with valacyclovir and doxycycline was started.During the next 2 days, the ulcers did not abate and the rectal pain worsened, such that the patient was not able to sit, sleep, or have bowel movements. Additional skin lesions appeared. The patient returned to the infectious disease clinic for evaluation. Anoscopy revealed intense rectal and anal inflammation with shallow ulcerations and purulent exudate, findings consistent with proctitis (Fig. 3). The patient was admitted to this hospital.
On examination, the patient appeared uncomfortable because of rectal pain. Skin lesions that had become pustular with an erythematous 
base were scattered across the scalp, chest, back, legs, and arms, including one on the palm (Fig. 2C). There were no lesions in the mouth. 
Multiple tender, enlarged inguinal lymph nodes, measuring more than 1 cm in diameter, were present. The perianal and penile ulcers were tender and had heaped margins around a central dry base. The complete blood count and the white-cell differential count were normal. Swabs from a perianal ulcer and a chest skin lesion were obtained for bacterial culture.Treatment with intravenous acyclovir was 
started, and doxycycline was continued; stool softeners and hydromorphone were administered. A blood test for HIV type 1 RNA was 
performed. A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with perianal and penile ulcers, rectal pain, and a vesiculopustular rash. He has a history of syphilis and recurrent oral herpes simplex virus (HSV) infection. His recent sexual history and the presence of ulcers and rash suggest a sexually transmitted infection. The patient's symptoms did not improve with valacyclovir, which is typically effective against HSV, suggesting that the cause of his symptoms is not HSV. The patient's blood test for treponemal antibodies was positive and a rapid plasma reagin (RPR) test was reactive, indicating a current or past syphilis infection. However, the patient was previously treated for syphilis and his symptoms did not improve with penicillin, which is the treatment of choice for syphilis. This suggests that his current symptoms are not due to syphilis. The patient's blood test for HIV was nonreactive, ruling out HIV as the cause of his symptoms. The patient's symptoms worsened over time and additional skin lesions appeared, suggesting a progressive disease. The patient's symptoms and the progression of his disease suggest a diagnosis of Lymphogranuloma venereum (LGV), a sexually transmitted infection caused by the L1, L2, L2b or L3 serovars of Chlamydia trachomatis.\n\nDiagnosis: Lymphogranuloma venereum (LGV)""
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        ""content"": ""The patient presents with perianal and penile ulcers, rectal pain, and a vesiculopustular rash. He has a history of syphilis and recurrent oral herpes simplex virus (HSV) infection. His recent sexual history and the presence of ulcers and rash suggest a sexually transmitted infection. The patient's symptoms did not improve with valacyclovir, which is typically effective against HSV, suggesting that the cause of his symptoms is not HSV. The patient's RPR test was reactive, indicating that he may have a current or past syphilis infection. However, he was previously treated for syphilis and his symptoms did not improve with penicillin, which is the treatment of choice for syphilis. This suggests that his current symptoms are not due to syphilis. The patient's symptoms and history suggest a diagnosis of lymphogranuloma venereum (LGV), a sexually transmitted infection caused by certain types of Chlamydia trachomatis. LGV can cause genital and perianal ulcers, rectal pain, and inguinal lymphadenopathy, all of which are present in this patient. The patient's tests for Chlamydia trachomatis were negative, but these tests may not detect the types of Chlamydia trachomatis that cause LGV.\n\nDiagnosis: Lymphogranuloma venereum (LGV)""
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        ""content"": ""The patient is a 31-year-old man presenting with perianal and penile ulcers, rectal pain, and a vesiculopustular rash. He has a history of secondary syphilis and recurrent oral herpes simplex virus (HSV) infection. He also has a history of unprotected sex with multiple partners. The differential diagnosis for this patient includes sexually transmitted infections such as syphilis, gonorrhea, chlamydia, and herpes, as well as other conditions that can cause similar symptoms such as Crohn's disease, Behcet's disease, and HIV. \n\nTests for HIV, syphilis, gonorrhea, and chlamydia were performed. The patient tested positive for treponemal antibodies and his RPR test was reactive at a dilution of 1:1, indicating a current or past syphilis infection. His HIV test was nonreactive, and tests for Neisseria gonorrhoeae and Chlamydia trachomatis were negative. A test for HSV nucleic acids was also performed. \n\nThe patient's symptoms did not improve with treatment, and additional skin lesions appeared. Anoscopy revealed intense rectal and anal inflammation with shallow ulcerations and purulent exudate, consistent with proctitis. \n\nGiven the patient's history and the results of his tests, the most likely diagnosis is a recurrent syphilis infection. The patient's symptoms, including the perianal and penile ulcers, rectal pain, and vesiculopustular rash, are consistent with this diagnosis. His positive RPR test also supports this diagnosis. \n\nDiagnosis: Recurrent syphilis infection.""
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10.1056/NEJMcpc2115858,Case 23-2022: A 49-Year-Old Man with Hypoglycemia,Alanine aminotransferase (U/liter) 5–34 33 Aspartate aminotransferase (U/liter) 6–55 28 Alkaline phosphatase (U/liter)   105 Lipase (U/liter) 13–60 67 Albumin (g/dl)   4.4 Sodium (mmol/liter)   138 Potassium (mmol/liter)   3.8 Chloride (mmol/liter) 98–107 103 Carbon dioxide (mmol/liter) 21–30 24 Urea nitrogen (mg/dl)   12 Creatinine (mg/dl)   1.03 Glucose (mg/dl) 70–109 36 Serum toxicologic panel Ethanol (mg/dl) 0.0 0.0 Salicylates (mg/dl) 0. 0.0,Well-differentiated pancreatic insulin-secreting neuroendocrine tumor (insulinoma).,Insulinoma,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 49-year-old man was admitted to this hospital because of hypoglycemia. The patient had been well until 3 hours before this admission, when altered mental status developed while he was at work. During a meeting, his colleagues noticed that he was not paying attention or participating in the conversation, which was atypical of the patient. Instead, he was fidgeting and mumbling as though talking to another person. When his mobile telephone rang, he allowed it to continue ringing. Two hours before this admission, the patient was found by colleagues on the floor of a conference room. His eyes were open, but he was obtunded and making nonpurposeful movements. Emergency medical services were called. On evaluation, a fingerstick glucose measurement was 39 mg per deciliter (2.2 mmol per liter; reference range, 70 to 109 mg per deciliter [3.9 to 6.1 mmol per liter]). Intravenous dextrose was administered, and the patient was brought to the emergency department of this hospital for further evaluation. On arrival at the emergency department, the patient was obtunded and did not react to sternal rub. Additional intravenous dextrose was administered, and a dextrose infusion was started. The patient’s mental status improved, and he was able to provide additional history. That morning, he had felt that he was in a “dreamlike” state; there were no other symptoms. The altered mental status had resolved, but he could not recall most events of the morning, including the meeting that had taken place 3 hours before admission. Review of symptoms was notable for unintentional weight gain of one pant size during the past 3 months, as well as intermittent morning dizziness during the past 3 years, which would resolve after the patient ate candy or breakfast. He reported no recent illness, depression, anxiety, change in activity or exercise, or change in intake of food or drink. On a typical day, he had breakfast at 5 a.m., a second breakfast at 10 a.m., lunch at 1 p.m., dinner at 6 p.m., and a snack at 8 p.m. The patient had last eaten approximately 7 hours before presentation to the emergency department. From the Departments of Medicine (A.W.B., N.J.W., B.W.C.), Radiology (P.F.H.), and Pathology (M.L.Z.), Massachusetts General Hospital, and the Departments of Medicine (A.W.B., N.J.W., B.W.C.), Ra‑ diology (P.F.H.), and Pathology (M.L.Z.), Harvard Medical School — both in Boston. N Engl J Med 2022;387:356-65. DOI: 10.1056/NEJMcpc2115858 Copyright © 2022 Massachusetts Medical Society. Founded by Richard C. Cabot Eric S. Rosenberg, M.D., Editor David M. Dudzinski, M.D., Meridale V. Baggett, M.D., Kathy M. Tran, M.D., Dennis C. Sgroi, M.D., Jo‑Anne O. Shepard, M.D., Associate Editors Emily K. McDonald, Tara Corpuz, Production Editors Case 23-2022: A 49-Year-Old Man with Hypoglycemia Amy W. Baughman, M.D., Nancy J. Wei, M.D., Peter F. Hahn, M.D., Ph.D., Brenna W. Casey, M.D., and M. Lisa Zhang, M.D. Case Records of the Massachusetts General Hospital CME at NEJM.org n engl j med 387;4 nejm.org July 28, 2022 357 Case Records of the Massachusetts General Hospital Two years earlier, the patient had had an episode of drooping and decreased sensation of the left side of the face and difficulty enunciating words, which occurred while he was at work. He presented to the emergency department of this hospital. The blood glucose level was 64 mg per deciliter (3.6 mmol per liter), and testing for Lyme disease was negative. He received a diagnosis of Bell’s palsy and was treated with prednisone and acyclovir; the symptoms resolved. Two months later, the patient established care in the primary care clinic of this hospital. Routine laboratory testing revealed a blood glucose level of 46 mg per deciliter (2.6 mmol per liter). The patient took vitamin B12 and vitamin D supplements. He took no other medications and had no known drug allergies. He drank alcohol rarely and did not smoke tobacco or use illicit drugs. Sixteen years earlier, he had immigrated to the United States from Southeast Asia and now lived alone in an urban area of New England. He worked as a registered nurse. His father and brother had type 2 diabetes and used insulin. On examination, the temperature was 35.7°C, the heart rate 82 beats per minute, the blood pressure 146/76 mm Hg, and the respiratory rate 14 breaths per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 27.6. The patient appeared well. He had no hepatosplenomegaly or skin hyperpigmentation, and the remainder of the physical examination was normal. On arrival at the emergency department, the blood glucose level was 36 mg per deciliter (2.0 mmol per liter); after the administration of dextrose, a fingerstick glucose measurement was 158 mg per deciliter (8.8 mmol per liter). The complete blood count and blood electrolyte levels were normal, as were the results of liverfunction and kidney-function tests. The glycated hemoglobin level was 5.4% (reference range, 4.3 to 6.4). Serum and urine toxicologic panels were negative. Laboratory test results are shown in Table 1. The patient was admitted to this hospital. A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 49-year-old man was admitted to this hospital because of hypoglycemia. The patient had been well until 3 hours before this admission, when altered mental status developed while he was at work. During a meeting, his colleagues noticed that he was not paying attention or participating in the conversation, which was atypical of the patient. Instead, he was fidgeting and mumbling as though talking to another person. When his mobile telephone rang, he allowed it to continue ringing. Two hours before this admission, the patient was found by colleagues on the floor of a conference room. His eyes were open, but he was obtunded and making nonpurposeful movements. Emergency medical services were called. On evaluation, a fingerstick glucose measurement was 39 mg per deciliter (2.2 mmol per liter; reference range, 70 to 109 mg per deciliter [3.9 to 6.1 mmol per liter]). Intravenous dextrose was administered, and the patient was brought to the emergency department of this hospital for further evaluation. On arrival at the emergency department, the patient was obtunded and did not react to sternal rub. Additional intravenous dextrose was administered, and a dextrose infusion was started. The patient’s mental status improved, and he was able to provide additional history. That morning, he had felt that he was in a “dreamlike” state; there were no other symptoms. The altered mental status had resolved, but he could not recall most events of the morning, including the meeting that had taken place 3 hours before admission. Review of symptoms was notable for unintentional weight gain of one pant size during the past 3 months, as well as intermittent morning dizziness during the past 3 years, which would resolve after the patient ate candy or breakfast. He reported no recent illness, depression, anxiety, change in activity or exercise, or change in intake of food or drink. On a typical day, he had breakfast at 5 a.m., a second breakfast at 10 a.m., lunch at 1 p.m., dinner at 6 p.m., and a snack at 8 p.m. The patient had last eaten approximately 7 hours before presentation to the emergency department. From the Departments of Medicine (A.W.B., N.J.W., B.W.C.), Radiology (P.F.H.), and Pathology (M.L.Z.), Massachusetts General Hospital, and the Departments of Medicine (A.W.B., N.J.W., B.W.C.), Ra‑ diology (P.F.H.), and Pathology (M.L.Z.), Harvard Medical School — both in Boston. N Engl J Med 2022;387:356-65. DOI: 10.1056/NEJMcpc2115858 Copyright © 2022 Massachusetts Medical Society. Founded by Richard C. Cabot Eric S. Rosenberg, M.D., Editor David M. Dudzinski, M.D., Meridale V. Baggett, M.D., Kathy M. Tran, M.D., Dennis C. Sgroi, M.D., Jo‑Anne O. Shepard, M.D., Associate Editors Emily K. McDonald, Tara Corpuz, Production Editors Case 23-2022: A 49-Year-Old Man with Hypoglycemia Amy W. Baughman, M.D., Nancy J. Wei, M.D., Peter F. Hahn, M.D., Ph.D., Brenna W. Casey, M.D., and M. Lisa Zhang, M.D. Case Records of the Massachusetts General Hospital CME at NEJM.org n engl j med 387;4 nejm.org July 28, 2022 357 Case Records of the Massachusetts General Hospital Two years earlier, the patient had had an episode of drooping and decreased sensation of the left side of the face and difficulty enunciating words, which occurred while he was at work. He presented to the emergency department of this hospital. The blood glucose level was 64 mg per deciliter (3.6 mmol per liter), and testing for Lyme disease was negative. He received a diagnosis of Bell’s palsy and was treated with prednisone and acyclovir; the symptoms resolved. Two months later, the patient established care in the primary care clinic of this hospital. Routine laboratory testing revealed a blood glucose level of 46 mg per deciliter (2.6 mmol per liter). The patient took vitamin B12 and vitamin D supplements. He took no other medications and had no known drug allergies. He drank alcohol rarely and did not smoke tobacco or use illicit drugs. Sixteen years earlier, he had immigrated to the United States from Southeast Asia and now lived alone in an urban area of New England. He worked as a registered nurse. His father and brother had type 2 diabetes and used insulin. On examination, the temperature was 35.7°C, the heart rate 82 beats per minute, the blood pressure 146/76 mm Hg, and the respiratory rate 14 breaths per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 27.6. The patient appeared well. He had no hepatosplenomegaly or skin hyperpigmentation, and the remainder of the physical examination was normal. On arrival at the emergency department, the blood glucose level was 36 mg per deciliter (2.0 mmol per liter); after the administration of dextrose, a fingerstick glucose measurement was 158 mg per deciliter (8.8 mmol per liter). The complete blood count and blood electrolyte levels were normal, as were the results of liverfunction and kidney-function tests. The glycated hemoglobin level was 5.4% (reference range, 4.3 to 6.4). Serum and urine toxicologic panels were negative. Laboratory test results are shown in Table 1. The patient was admitted to this hospital. A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Insulinoma. The patient's symptoms of altered mental status, which improved with the administration of glucose, suggest hypoglycemia. His history of morning dizziness that resolved after eating also suggests reactive hypoglycemia. The unintentional weight gain could be due to increased food intake to counteract the hypoglycemic episodes. The fact that his father and brother have type 2 diabetes and use insulin suggests a possible genetic predisposition to insulin-related disorders. The normal glycated hemoglobin level rules out uncontrolled diabetes as a cause of hypoglycemia. The patient's occupation as a nurse could potentially give him access to insulin, but the negative toxicology screen rules out surreptitious insulin use. Therefore, an insulin-secreting tumor, or insulinoma, is the most likely diagnosis.""
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        ""content"": ""The patient's symptoms of hypoglycemia, weight gain, and morning dizziness that resolves after eating suggest an issue with glucose regulation. The fact that his father and brother have type 2 diabetes and use insulin suggests a possible genetic predisposition to glucose regulation issues. However, his glycated hemoglobin level is normal, which suggests that he does not have diabetes. The patient's symptoms of hypoglycemia are severe, leading to altered mental status and obtundation. This suggests a possible insulinoma, a tumor of the pancreas that produces insulin. This would cause episodes of hypoglycemia, especially after periods of fasting, as insulin lowers blood glucose levels. The patient's symptoms improve after eating, which would raise blood glucose levels. \n\nDiagnosis: Insulinoma.""
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        ""content"": ""The patient is a 49-year-old man presenting with hypoglycemia and altered mental status. The differential diagnosis for hypoglycemia includes insulinoma, non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), insulin overdose, and other endocrine disorders such as adrenal insufficiency or hypopituitarism. The patient's history of unintentional weight gain and morning dizziness that resolves after eating suggests a possible insulinoma or NIPHS, both of which can cause hypoglycemia due to overproduction of insulin. The patient's family history of type 2 diabetes could suggest a predisposition to pancreatic disorders, but his glycated hemoglobin level is normal, which makes diabetes unlikely. The patient does not take insulin, which makes insulin overdose unlikely. The patient does not have symptoms of adrenal insufficiency such as fatigue, weight loss, or hyperpigmentation, making this diagnosis less likely. The patient's normal complete blood count and electrolyte levels also make adrenal insufficiency and hypopituitarism less likely. Given the patient's symptoms and the results of his laboratory tests, the most likely diagnosis is an insulinoma or NIPHS.\n\nDiagnosis: Insulinoma or Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS)""
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10.1056/NEJMcpc2201238,Case 22-2022: A 34-Year-Old Woman with Cavitary Lung Lesions,"Hematocrit (%) 34.9–44.4 26.4   30.9 24.1
Hemoglobin (g/dl) 11.6–15.2 8.0   9.2 7.0
White-cell count (per μl) 4000–12,400 3130   2240 5330
Differential count (%)
Neutrophils 40.0–74.0 85.3   83.5 83.0
Lymphocytes 19.0–48.0 5.1   7.6 8.2
Monocytes 3.0–9.0 8.3 4. .0 6.7 3.6
Eosinophils 0–7 0   0 0
Basophils 0–1 0 0. .0 0.0 0.2
Bands 0.0–7.0 1.3 0.0–10.0 2.2 4.9
Platelet count (per μl) 141,00 77,000 139,000   117,000 81,000
Mean corpuscular volume (fl) 81.0–99.0 80.0   78.2 81.7",Infection with Blastomyces dermatitidis.,Blastomycosis,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 34-year-old woman was admitted to this hospital with hypercortisolism in the context of a metastatic pancreatic neuroendocrine tumor.
The patient had been well until 4 years before this presentation, when abdominal pain, diarrhea, and ascites developed. A pancreatic neuroendocrine tumor with metastases to the liver and spleen was ultimately diagnosed, and treatment with octreotide and everolimus was initiated.
Three years before this presentation, treatment with peptide receptor radionuclide therapy was initiated; four cycles were completed over the course of the next 2 years. Eight months before this presentation, the patient decided to stop taking everolimus because of fatigue.
Seven months before this presentation, the patient was evaluated at another hospital because of weight gain, hyperglycemia, and changes in mood. She was found to have elevated blood levels of corticotropin and elevated salivary and urinary levels of cortisol.
Dr. Adina Haramati: Magnetic resonance imaging (MRI) of the head revealed a pituitary lesion measuring 1.3 cm in greatest dimension. A specimen of blood obtained from the inferior petrosal sinus identified a pituitary source of corticotropin secretion.
Dr. Pak: Treatment with octreotide was discontinued, and 3 months before this presentation, transsphenoidal resection of the pituitary lesion was performed. After the surgery, the cortisol and corticotropin levels remained elevated. Repeat MRI of the head revealed a residual pituitary lesion. Transsphenoidal resection of the residual lesion was performed 2 months before this presentation.
After the second surgery, the cortisol and corticotropin levels decreased but did not normalize. Pathological evaluation of a resected pituitary specimen revealed normal anterior pituitary architecture that was not consistent with a corticotroph adenoma. At a follow-up appointment in the endocrinology clinic after the patient was discharged, the 24-hour urinary free cortisol level was again elevated, and treatment with pasireotide was initiated.
Ten days before this presentation, the patient began to have confusion, urinary incontinence, and recurrent falls. She was evaluated in the emergency department of another hospital. Her husband noted atypical impulsive behaviors, such as online shopping and excessive eating.
Dr. Haramati: MRI of the head revealed a small focus of decreased enhancement within the left inferior aspect of the sella turcica, a finding that was consistent with postsurgical changes or residual adenoma.
Dr. Pak: A morning blood level of cortisol was 80 [mu]g per deciliter (2207 nmol per liter; reference range, 4 to 23 [mu]g per deciliter [110 to 635 nmol per liter]), and the blood level of corticotropin was 519 pg per milliliter (114 pmol per liter; reference range, 7.2 to 63 pg per milliliter [1.6 to 14 pmol per liter]). The 24-hour urinary free cortisol level was 9450 [mu]g (26,069 nmol per liter; reference range, 3.5 to 45 [mu]g [10 to 124 nmol per liter]).
Dr. Haramati: MRI of the abdomen revealed an exophytic mass on the pancreatic tail that broadly abutted the left adrenal gland, thickening of both adrenal glands, retroperitoneal metastases on the left side, and extensive hepatic metastases with chronic cavernous transformation of the portal vein.
Dr. Pak: Treatment with pasireotide was discontinued, and treatment with ketoconazole was initiated, in addition to potassium supplementation and spironolactone for hypokalemia. On the tenth day at the other hospital, the patient was transferred to this hospital for further treatment.
On evaluation at this hospital, the patient reported fatigue but no fever, chills, night sweats, or weight loss. She had no cough, hemoptysis, or chest pain; no rheumatologic symptoms; and no history of dysphagia or gastroesophageal reflux disease. Her medical history included asthma and portal-vein thrombosis complicated by ascites, as well as hypothyroidism and central diabetes insipidus after she had undergone transsphenoidal resection of the pituitary lesions. Medications included atovaquone, cholecalciferol, desmopressin, ketoconazole, levothyroxine, metformin, pantoprazole, spironolactone, and potassium chloride. She had no known drug allergies. She did not drink alcohol or use tobacco or vaping products; she smoked marijuana occasionally. She lived with her husband in Vermont and had previously worked in a health care facility. The patient reported that she had had several skin tests for Mycobacterium tuberculosis owing to her work in the health care setting, and none had been positive. Before her illness, she had frequently gardened and hiked locally. She had traveled to Canada but otherwise had not traveled outside New England. A paternal aunt had had ovarian cancer.
On examination, the temperature was 36.9[degrees]C, the blood pressure 152/87 mm Hg, the pulse 77 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.0. The patient was alert and oriented and answered questions appropriately. Her face was rounded, and acne and hair thinning were present. The abdomen had increased adiposity and palpable striae. There were several bruises on her arms and legs. A chest radiograph obtained on admission to this hospital showed an implanted venous access device and a patchy opacity in the right upper lung zone.
Treatment with octreotide was reinitiated, and treatment with the other medications that the patient had been receiving was continued. The hypercortisolism was thought to be due to secretion of corticotropin from the metastatic pancreatic neuroendocrine tumor. Bilateral adrenalectomy was planned, but on the second hospital day, the patient became withdrawn and would not speak, take any oral medications, or consume any food. She was transferred to the intensive care unit, and an etomidate infusion was initiated; the dose was adjusted to attain a blood level of cortisol between 10 and 20 [mu]g per deciliter. Subsequent treatment with intravenous lorazepam resulted in marked improvement in the patient's mental status such that she was following commands and responding appropriately to questions. On the sixth hospital day, bilateral adrenalectomy was performed. Treatment with intravenous hydrocortisone was initiated postoperatively, and on the seventh hospital day, the patient was transferred to the medicine unit of this hospital for further care.
Dr. Haramati: On the eighth hospital day, sinus tachycardia developed. Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material according to a pulmonary embolism protocol (Figure 1), revealed a patchy consolidation in the right upper lobe with areas of cavitation and adjacent tree-in-bud opacities, as well as small bilateral pleural effusions. There was no evidence of pulmonary embolism. Although previous imaging was not available for review, clinical notes indicated that positron-emission tomography-CT performed at another hospital 8 months before this presentation had revealed a new cavitary nodule in the right upper lobe that measured 7 mm in diameter.	
Figure 1 Figure 1
Dr. Pak: A sputum culture showed few squamous epithelial cells, rare polymorphonuclear leukocytes, and few mixed gram-positive and gram-negative organisms with no specific type predominating; no acid-fast bacilli were observed on a mycobacterial smear of an induced sputum sample. Urine tests for Legionella pneumophila and Streptococcus pneumoniae antigens were negative, as was a blood test for cryptococcal antigen. The blood level of 1,3-[beta]-d-glucan was less than 31 pg per milliliter (reference value, <60), and the blood galactomannan index was 0.05 (reference range, 0 to 0.49). Other laboratory test results are shown in Table 1.	

On the ninth hospital day, bronchoscopy was performed; bronchial washings and bronchoalveolar-lavage (BAL) samples were obtained, and no purulent secretions were observed. Gram's staining of the BAL fluid revealed few mixed gram-positive and gram-negative organisms, and no organisms were seen on an acid-fast bacilli smear or on a modified acid-fast bacilli smear. Examination of the BAL fluid for Pneumocystis jirovecii was negative.
On the 11th hospital day, culture of the BAL fluid showed growth of few methicillin-sensitive Staphylococcus aureus organisms. Treatment with intravenous vancomycin, cefepime, and metronidazole was initiated. On the 12th hospital day, a urine test for histoplasma antigen was positive, at a level of 2.25 ng per milliliter (reference ranges, 0.00 to 0.10 [negative]; 0.11 to 1.10 [indeterminate]; >=1.11 [positive]).
Management decisions were made, and results of a diagnostic test were received.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 34-year-old woman was admitted to this hospital with hypercortisolism in the context of a metastatic pancreatic neuroendocrine tumor.
The patient had been well until 4 years before this presentation, when abdominal pain, diarrhea, and ascites developed. A pancreatic neuroendocrine tumor with metastases to the liver and spleen was ultimately diagnosed, and treatment with octreotide and everolimus was initiated.
Three years before this presentation, treatment with peptide receptor radionuclide therapy was initiated; four cycles were completed over the course of the next 2 years. Eight months before this presentation, the patient decided to stop taking everolimus because of fatigue.
Seven months before this presentation, the patient was evaluated at another hospital because of weight gain, hyperglycemia, and changes in mood. She was found to have elevated blood levels of corticotropin and elevated salivary and urinary levels of cortisol.
Dr. Adina Haramati: Magnetic resonance imaging (MRI) of the head revealed a pituitary lesion measuring 1.3 cm in greatest dimension. A specimen of blood obtained from the inferior petrosal sinus identified a pituitary source of corticotropin secretion.
Dr. Pak: Treatment with octreotide was discontinued, and 3 months before this presentation, transsphenoidal resection of the pituitary lesion was performed. After the surgery, the cortisol and corticotropin levels remained elevated. Repeat MRI of the head revealed a residual pituitary lesion. Transsphenoidal resection of the residual lesion was performed 2 months before this presentation.
After the second surgery, the cortisol and corticotropin levels decreased but did not normalize. Pathological evaluation of a resected pituitary specimen revealed normal anterior pituitary architecture that was not consistent with a corticotroph adenoma. At a follow-up appointment in the endocrinology clinic after the patient was discharged, the 24-hour urinary free cortisol level was again elevated, and treatment with pasireotide was initiated.
Ten days before this presentation, the patient began to have confusion, urinary incontinence, and recurrent falls. She was evaluated in the emergency department of another hospital. Her husband noted atypical impulsive behaviors, such as online shopping and excessive eating.
Dr. Haramati: MRI of the head revealed a small focus of decreased enhancement within the left inferior aspect of the sella turcica, a finding that was consistent with postsurgical changes or residual adenoma.
Dr. Pak: A morning blood level of cortisol was 80 [mu]g per deciliter (2207 nmol per liter; reference range, 4 to 23 [mu]g per deciliter [110 to 635 nmol per liter]), and the blood level of corticotropin was 519 pg per milliliter (114 pmol per liter; reference range, 7.2 to 63 pg per milliliter [1.6 to 14 pmol per liter]). The 24-hour urinary free cortisol level was 9450 [mu]g (26,069 nmol per liter; reference range, 3.5 to 45 [mu]g [10 to 124 nmol per liter]).
Dr. Haramati: MRI of the abdomen revealed an exophytic mass on the pancreatic tail that broadly abutted the left adrenal gland, thickening of both adrenal glands, retroperitoneal metastases on the left side, and extensive hepatic metastases with chronic cavernous transformation of the portal vein.
Dr. Pak: Treatment with pasireotide was discontinued, and treatment with ketoconazole was initiated, in addition to potassium supplementation and spironolactone for hypokalemia. On the tenth day at the other hospital, the patient was transferred to this hospital for further treatment.
On evaluation at this hospital, the patient reported fatigue but no fever, chills, night sweats, or weight loss. She had no cough, hemoptysis, or chest pain; no rheumatologic symptoms; and no history of dysphagia or gastroesophageal reflux disease. Her medical history included asthma and portal-vein thrombosis complicated by ascites, as well as hypothyroidism and central diabetes insipidus after she had undergone transsphenoidal resection of the pituitary lesions. Medications included atovaquone, cholecalciferol, desmopressin, ketoconazole, levothyroxine, metformin, pantoprazole, spironolactone, and potassium chloride. She had no known drug allergies. She did not drink alcohol or use tobacco or vaping products; she smoked marijuana occasionally. She lived with her husband in Vermont and had previously worked in a health care facility. The patient reported that she had had several skin tests for Mycobacterium tuberculosis owing to her work in the health care setting, and none had been positive. Before her illness, she had frequently gardened and hiked locally. She had traveled to Canada but otherwise had not traveled outside New England. A paternal aunt had had ovarian cancer.
On examination, the temperature was 36.9[degrees]C, the blood pressure 152/87 mm Hg, the pulse 77 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.0. The patient was alert and oriented and answered questions appropriately. Her face was rounded, and acne and hair thinning were present. The abdomen had increased adiposity and palpable striae. There were several bruises on her arms and legs. A chest radiograph obtained on admission to this hospital showed an implanted venous access device and a patchy opacity in the right upper lung zone.
Treatment with octreotide was reinitiated, and treatment with the other medications that the patient had been receiving was continued. The hypercortisolism was thought to be due to secretion of corticotropin from the metastatic pancreatic neuroendocrine tumor. Bilateral adrenalectomy was planned, but on the second hospital day, the patient became withdrawn and would not speak, take any oral medications, or consume any food. She was transferred to the intensive care unit, and an etomidate infusion was initiated; the dose was adjusted to attain a blood level of cortisol between 10 and 20 [mu]g per deciliter. Subsequent treatment with intravenous lorazepam resulted in marked improvement in the patient's mental status such that she was following commands and responding appropriately to questions. On the sixth hospital day, bilateral adrenalectomy was performed. Treatment with intravenous hydrocortisone was initiated postoperatively, and on the seventh hospital day, the patient was transferred to the medicine unit of this hospital for further care.
Dr. Haramati: On the eighth hospital day, sinus tachycardia developed. Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material according to a pulmonary embolism protocol (Figure 1), revealed a patchy consolidation in the right upper lobe with areas of cavitation and adjacent tree-in-bud opacities, as well as small bilateral pleural effusions. There was no evidence of pulmonary embolism. Although previous imaging was not available for review, clinical notes indicated that positron-emission tomography-CT performed at another hospital 8 months before this presentation had revealed a new cavitary nodule in the right upper lobe that measured 7 mm in diameter.	
Figure 1 Figure 1
Dr. Pak: A sputum culture showed few squamous epithelial cells, rare polymorphonuclear leukocytes, and few mixed gram-positive and gram-negative organisms with no specific type predominating; no acid-fast bacilli were observed on a mycobacterial smear of an induced sputum sample. Urine tests for Legionella pneumophila and Streptococcus pneumoniae antigens were negative, as was a blood test for cryptococcal antigen. The blood level of 1,3-[beta]-d-glucan was less than 31 pg per milliliter (reference value, <60), and the blood galactomannan index was 0.05 (reference range, 0 to 0.49). Other laboratory test results are shown in Table 1.	

On the ninth hospital day, bronchoscopy was performed; bronchial washings and bronchoalveolar-lavage (BAL) samples were obtained, and no purulent secretions were observed. Gram's staining of the BAL fluid revealed few mixed gram-positive and gram-negative organisms, and no organisms were seen on an acid-fast bacilli smear or on a modified acid-fast bacilli smear. Examination of the BAL fluid for Pneumocystis jirovecii was negative.
On the 11th hospital day, culture of the BAL fluid showed growth of few methicillin-sensitive Staphylococcus aureus organisms. Treatment with intravenous vancomycin, cefepime, and metronidazole was initiated. On the 12th hospital day, a urine test for histoplasma antigen was positive, at a level of 2.25 ng per milliliter (reference ranges, 0.00 to 0.10 [negative]; 0.11 to 1.10 [indeterminate]; >=1.11 [positive]).
Management decisions were made, and results of a diagnostic test were received.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Disseminated Histoplasmosis\n\nThe patient's symptoms of confusion, urinary incontinence, recurrent falls, and impulsive behaviors, along with her history of a metastatic pancreatic neuroendocrine tumor and hypercortisolism, suggest a systemic infection. The patient's CT scan revealed a patchy consolidation in the right upper lobe with areas of cavitation and adjacent tree-in-bud opacities, which are indicative of an infectious process. The positive urine test for histoplasma antigen confirms the diagnosis of disseminated histoplasmosis. Histoplasmosis is a fungal infection that can cause a wide range of symptoms and is often severe in patients with weakened immune systems, such as this patient with a history of cancer and hypercortisolism.""
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        ""content"": ""Disseminated histoplasmosis. The patient's positive urine test for histoplasma antigen, along with her symptoms of fatigue, weight gain, hyperglycemia, and changes in mood, as well as her history of a metastatic pancreatic neuroendocrine tumor, all point to this diagnosis. Histoplasmosis is a fungal infection that can cause a wide range of symptoms and can become disseminated in individuals with weakened immune systems, such as this patient with a history of cancer.""
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        ""content"": ""The patient is a 34-year-old woman with a history of a metastatic pancreatic neuroendocrine tumor and hypercortisolism. She presents with weight gain, hyperglycemia, mood changes, confusion, urinary incontinence, recurrent falls, and impulsive behaviors. She also has a rounded face, acne, hair thinning, increased abdominal adiposity, palpable striae, and several bruises on her arms and legs. These symptoms are consistent with Cushing's syndrome, which is caused by prolonged exposure to high levels of cortisol. The patient's hypercortisolism is thought to be due to secretion of corticotropin from the metastatic pancreatic neuroendocrine tumor. The patient also has a positive urine test for histoplasma antigen, indicating a Histoplasma infection. Histoplasmosis is a fungal infection that primarily affects the lungs and can cause a variety of respiratory symptoms. The patient's immunocompromised state due to her cancer and hypercortisolism likely made her more susceptible to this infection. \n\nDiagnosis: Cushing's syndrome due to ectopic ACTH secretion from a metastatic pancreatic neuroendocrine tumor and Histoplasmosis.""
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10.1056/NEJMcpc2115851,Case 21-2022: A 17-Year-Old Girl with Fever and Cough,"Hemoglobin (g/dl)   6.7 Hematocrit (%)   21.1 Platelet count (per μl)   526,000 White-cell count (per μl) 450 ,000 11,890 Differential count (per μl) Neutrophils 180 100 8810 Lymphocytes 1200–5200 1760 Monocytes 20 00 880 Eosinophils 0–1000 330 Basophils  0 50 Creatinine (mg/dl)   2.00 Urea nitrogen (mg/dl)   22 Sodium (mmol/liter)   136 Potassium (mmol/liter)   4.3 Chloride (mmol/liter)   99 Carbon dioxide (mmol/liter)   24 Lactate dehydrogenase (U/liter) 11 10 462 C-reactive protein (mg/liter)",Granulomatosis with polyangiitis,Granulomatosis with polyangiitis,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 17-year-old girl was admitted to this hospital during the coronavirus disease 2019 (Covid-19) pandemic because of fever and 
cough.The patient had been well until 10 days before admission, when fever and cough  that was productive of clear sputum developed. She also had fatigue, eye redness, sore throat, nasal congestion, rhinorrhea, and myalgias. Seven days before this admission, the patient was evaluated in the urgent care clinic of another hospital. On examination, there was conjunctival injection in 
both eyes. The lungs were clear on auscultation, and the remainder of the physical examination was reportedly normal. Testing of a nasopharyngeal specimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative. 
Treatment with acetaminophen and dextromethorphan was recommended.During the next 2 days, the fever decreased but did not resolve with the use of acetaminophen. New mild chest discomfort occurred with coughing. An expectorated sputum specimen contained flecks of blood, and the patient returned to the urgent care clinic. The physical examination was unchanged, and rapid antigen testing for influenza types A and B was negative. Additional treatment with ibuprofen, benzonatate, and guaifenesin was recommended.Three days before this admission, the patient had persistent symptoms and was unable to sleep because of the fever and cough. New shortness of breath developed. She was evaluated by a primary care physician at the other hospital in a telehealth visit. Empirical treatment with amoxicillin was started, and close monitoring was recommended. During the next 3 days, the shortness of breath increased in severity, and the patient was instructed to present to the emergency department of this hospital.On evaluation, the patient reported cough that was worse with exertion and deep breathing, improved with rest, and was associated with pain in the chest and back on the left side. The sputum had streaks of bright red blood. Other symptoms included fatigue, sore throat, nasal congestion, rhinorrhea, myalgias, and pain in both knees when walking. The eye redness had resolved, but there was mild soreness of the right eye. There was no headache, ear pain, difficulty 
swallowing, abdominal pain, nausea, vomiting, diarrhea, or rash.The patient had a history of developmental dysplasia of the hip and was otherwise healthy. She had normal growth and development and had received all routine childhood vaccinations. Medications includedamoxicillin, acetaminophen, ibuprofen, benzonatate, guaifenesin, and dextromethorphan. There were no known drug allergies. The patient was born in New England and lived in a suburban area of New England with her mother, father, and brother. She performed well in high school, which she was attending remotely because of the Covid-19 pandemic; she had no known sick contacts. She had traveled to 
a Caribbean island 1 year earlier. She was a vegetarian and did not drink alcohol, smoke tobacco, or use illicit drugs. Her parents and brother were healthy. On examination, the temperature was 38.5°C, the heart rate 124 beats per minute, the blood pressure 142/62 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. 
The body-mass index (the weight in kilograms divided by the square of the height in meters) was 35.9. The patient appeared pale, and she coughed and sniffled frequently. She did not use accessory muscles while breathing, and breath sounds in the lower lung fields were decreased. There was no conjunctival injection, lymphadenopathy, joint swelling or tenderness, or rash; the remainder of the physical examination was normal.
The creatinine level was 2.00 mg per deciliter (177 μmol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 μmol per liter]) and the C-reactive protein level 77.5 mg per liter (reference value,  .0). The hemoglobin level was 6.7 g per deciliter (reference range, 12.0 to 16.0), the hematocrit 21.1% (reference range, 36.0 to 46.0), the white-cell count 11,890 per microliter (reference range, 4500 to 13,000), and the platelet count 526,000 per microliter (reference range, 150,000 to 450,000). Urinalysis revealed 3+ blood and 2+ protein; microscopic examination of the urinary sediment revealed more than 100 red cells per high-power field (reference range, 0 to 2) and 10 to 20 white cells per high-power field (reference value,  ), as well as mixed granular casts and red-cell casts. Nucleic acid testing of a nasopharyngeal specimen for SARS-CoV-2, influenza types A and B, and respiratory syncytial virus was negative. An interferon-γ release assay for Mycobacterium tuberculosis was performed, and blood cultures were obtained. Other laboratory test results are shown in Table 1.
Dr. Randheer Shailam: Chest radiography (Fig. 1A and 1B) revealed prominent patchy opacities in the lower lung zones. Computed tomography (CT) of the chest (Fig. 1C through 1F), performed without the administration of intravenous contrast material, revealed peripheral patchy ground-glass opacification with greater involvement of the lower lobes than of the upper lobes, the lingula (left lung), and the middle lobe (right lung). There were also areas of normal-appearing lung. These findings are not specific and can be seen with infectious causes such as bacterial pneumonia and Covid-19, as well as with noninfectious causes such as aspiration, pulmonary hemorrhage, and less likely, alveolar proteinosis.
Dr. Martin: Ceftriaxone, azithromycin, and intravenous fluids were administered. A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 17-year-old girl was admitted to this hospital during the coronavirus disease 2019 (Covid-19) pandemic because of fever and 
cough.The patient had been well until 10 days before admission, when fever and cough  that was productive of clear sputum developed. She also had fatigue, eye redness, sore throat, nasal congestion, rhinorrhea, and myalgias. Seven days before this admission, the patient was evaluated in the urgent care clinic of another hospital. On examination, there was conjunctival injection in 
both eyes. The lungs were clear on auscultation, and the remainder of the physical examination was reportedly normal. Testing of a nasopharyngeal specimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative. 
Treatment with acetaminophen and dextromethorphan was recommended.During the next 2 days, the fever decreased but did not resolve with the use of acetaminophen. New mild chest discomfort occurred with coughing. An expectorated sputum specimen contained flecks of blood, and the patient returned to the urgent care clinic. The physical examination was unchanged, and rapid antigen testing for influenza types A and B was negative. Additional treatment with ibuprofen, benzonatate, and guaifenesin was recommended.Three days before this admission, the patient had persistent symptoms and was unable to sleep because of the fever and cough. New shortness of breath developed. She was evaluated by a primary care physician at the other hospital in a telehealth visit. Empirical treatment with amoxicillin was started, and close monitoring was recommended. During the next 3 days, the shortness of breath increased in severity, and the patient was instructed to present to the emergency department of this hospital.On evaluation, the patient reported cough that was worse with exertion and deep breathing, improved with rest, and was associated with pain in the chest and back on the left side. The sputum had streaks of bright red blood. Other symptoms included fatigue, sore throat, nasal congestion, rhinorrhea, myalgias, and pain in both knees when walking. The eye redness had resolved, but there was mild soreness of the right eye. There was no headache, ear pain, difficulty 
swallowing, abdominal pain, nausea, vomiting, diarrhea, or rash.The patient had a history of developmental dysplasia of the hip and was otherwise healthy. She had normal growth and development and had received all routine childhood vaccinations. Medications includedamoxicillin, acetaminophen, ibuprofen, benzonatate, guaifenesin, and dextromethorphan. There were no known drug allergies. The patient was born in New England and lived in a suburban area of New England with her mother, father, and brother. She performed well in high school, which she was attending remotely because of the Covid-19 pandemic; she had no known sick contacts. She had traveled to 
a Caribbean island 1 year earlier. She was a vegetarian and did not drink alcohol, smoke tobacco, or use illicit drugs. Her parents and brother were healthy. On examination, the temperature was 38.5°C, the heart rate 124 beats per minute, the blood pressure 142/62 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. 
The body-mass index (the weight in kilograms divided by the square of the height in meters) was 35.9. The patient appeared pale, and she coughed and sniffled frequently. She did not use accessory muscles while breathing, and breath sounds in the lower lung fields were decreased. There was no conjunctival injection, lymphadenopathy, joint swelling or tenderness, or rash; the remainder of the physical examination was normal.
The creatinine level was 2.00 mg per deciliter (177 μmol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 μmol per liter]) and the C-reactive protein level 77.5 mg per liter (reference value,  .0). The hemoglobin level was 6.7 g per deciliter (reference range, 12.0 to 16.0), the hematocrit 21.1% (reference range, 36.0 to 46.0), the white-cell count 11,890 per microliter (reference range, 4500 to 13,000), and the platelet count 526,000 per microliter (reference range, 150,000 to 450,000). Urinalysis revealed 3+ blood and 2+ protein; microscopic examination of the urinary sediment revealed more than 100 red cells per high-power field (reference range, 0 to 2) and 10 to 20 white cells per high-power field (reference value,  ), as well as mixed granular casts and red-cell casts. Nucleic acid testing of a nasopharyngeal specimen for SARS-CoV-2, influenza types A and B, and respiratory syncytial virus was negative. An interferon-γ release assay for Mycobacterium tuberculosis was performed, and blood cultures were obtained. Other laboratory test results are shown in Table 1.
Dr. Randheer Shailam: Chest radiography (Fig. 1A and 1B) revealed prominent patchy opacities in the lower lung zones. Computed tomography (CT) of the chest (Fig. 1C through 1F), performed without the administration of intravenous contrast material, revealed peripheral patchy ground-glass opacification with greater involvement of the lower lobes than of the upper lobes, the lingula (left lung), and the middle lobe (right lung). There were also areas of normal-appearing lung. These findings are not specific and can be seen with infectious causes such as bacterial pneumonia and Covid-19, as well as with noninfectious causes such as aspiration, pulmonary hemorrhage, and less likely, alveolar proteinosis.
Dr. Martin: Ceftriaxone, azithromycin, and intravenous fluids were administered. A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with fever, cough, fatigue, eye redness, sore throat, nasal congestion, rhinorrhea, and myalgias. She also has a history of developmental dysplasia of the hip. Her symptoms have persisted despite treatment with acetaminophen, dextromethorphan, ibuprofen, benzonatate, guaifenesin, and amoxicillin. Her physical examination reveals decreased breath sounds in the lower lung fields. Laboratory findings show elevated creatinine and C-reactive protein levels, low hemoglobin and hematocrit levels, and elevated white-cell and platelet counts. Urinalysis reveals blood and protein, and microscopic examination of the urinary sediment reveals red cells, white cells, and mixed granular and red-cell casts. Chest radiography and CT reveal patchy opacities and ground-glass opacification in the lower lung zones. These findings suggest a systemic inflammatory response with involvement of the lungs and kidneys. The presence of red-cell casts in the urine is indicative of glomerulonephritis. Given the patient's age, the constellation of respiratory and renal involvement, and the negative results for infectious causes, an autoimmune process such as granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) should be considered.\n\nDiagnosis: Granulomatosis with polyangiitis.""
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        ""role"": ""assistant"",
        ""content"": ""The patient presents with fever, cough, fatigue, eye redness, sore throat, nasal congestion, rhinorrhea, and myalgias. She also has a history of developmental dysplasia of the hip. Her symptoms have not improved with antibiotics and she has developed shortness of breath. Her lab results show an elevated creatinine level, C-reactive protein level, and platelet count, and a decreased hemoglobin level and hematocrit. Her urinalysis shows blood and protein, and her chest radiography and CT show patchy opacities and ground-glass opacification. These findings suggest a systemic disease affecting multiple organs, including the lungs and kidneys. The presence of red-cell casts in the urine is indicative of glomerulonephritis. Given the patient's age, the acute onset of her symptoms, and the involvement of multiple organ systems, the most likely diagnosis is an autoimmune disease. The combination of lung and kidney involvement is characteristic of granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis. \n\nDiagnosis: Granulomatosis with polyangiitis (GPA)""
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        ""content"": ""The patient is a 17-year-old girl presenting with fever, cough, fatigue, eye redness, sore throat, nasal congestion, rhinorrhea, myalgias, and chest discomfort. She also has hemoptysis and shortness of breath. The differential diagnosis for this patient includes COVID-19, bacterial pneumonia, tuberculosis, and autoimmune diseases such as lupus or vasculitis. \n\nThe patient tested negative for SARS-CoV-2, influenza A and B, and respiratory syncytial virus, making these viral infections less likely. Her interferon-\u03b3 release assay for Mycobacterium tuberculosis was also negative, making tuberculosis less likely. \n\nThe patient's lab results show an elevated creatinine level, indicating kidney dysfunction, and an elevated C-reactive protein level, indicating inflammation. Her hemoglobin level is low, indicating anemia, and her platelet count is high. Her urinalysis shows blood and protein, as well as red and white cells and granular and red-cell casts, indicating glomerulonephritis. \n\nThe patient's chest radiography and CT show patchy opacities and ground-glass opacification in the lower lung zones, which can be seen in bacterial pneumonia, COVID-19, aspiration, pulmonary hemorrhage, and alveolar proteinosis. \n\nGiven the patient's symptoms, lab results, and imaging findings, an autoimmune disease such as lupus or vasculitis is likely. Both can cause glomerulonephritis, leading to the kidney dysfunction seen in the patient's lab results, and can cause inflammation in the lungs, leading to the findings on the patient's imaging. \n\nDiagnosis: \nGiven the patient's age, gender, and the constellation of symptoms, the most likely diagnosis is lupus with lupus nephritis and pulmonary involvement.""
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}",lupus with lupus nephritis and pulmonary involvement,N
10.1056/NEJMcpc2115854,Case 20-2022: A 25-Year-Old Man with Vision Changes,"Hemoglobin (g/dl)   9.3
Hematocrit (%)   29.0
Platelet count (per μl)   47,000
White-cell count (per μl)   5060
Differential count (per μl)
Neutrophils   3170
Lymphocytes   990
Monocytes   430
Eosinophils   380
Basophils  00 100
Sodium (mmol/liter)   134
Potassium (mmol/liter)   3.8
Chloride (mmol/liter)   103
Carbon dioxide (mmol/liter)   23
Urea nitrogen (mg/dl)   13
Creatinine (mg/dl)   1.04
Alanine aminotransferase (U/liter)   45
Aspartate aminotransferase (U/liter)   33
Alkaline phosphatase (U/liter)   43
Lactate dehydrogenase (U/liter) 11 10 192
Total protein (g/dl) 6. .3 10.7
Albumin (g/dl)   3.0
Globulin (g/dl)   7.7
IgA (mg/dl)   98
IgG (mg/dl)   6238
IgM (mg/dl)   26
Serum protein electrophoresis Normal pattern IgG kappa M component 
at a level of 5.18 g/dl 
in the gamma region
Free kappa light chain (mg/liter)   262.7
Free lambda light chain (mg/liter)   11.4
Free kappa:lambda ratio 0.30–1.70 23.04
Antinuclear antibody Negative Positive at 1:40
Anti-SSA, or anti-Ro, antibody Negative Negative
Anti-SSB, or anti-La, antibody Negative Negative
Anti–aquaporin-4 antibody Negative Negative
Anti–myelin oligodendrocyte glycoprotein antibody Negative Negative",Plasma-cell myeloma post-transplantation lymphoproliferative disorder.,Post-transplantation lymphoproliferative disorder.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 25-year-old man with a history of B-cell acute lymphoblastic leukemia was evaluated in the emergency department of this hospital because of vision changes.
Ten months before this presentation, the patient was evaluated for fatigue and dyspnea on exertion. Laboratory testing revealed a hemoglobin level of 3.5 g per deciliter (reference range, 13.5 to 17.5) and a white-cell count of 23,450 per microliter (reference range, 4000 to 11,000), with 81% lymphocytes and 4% blasts. A bone marrow biopsy was performed.
Dr. Judith A. Ferry: Examination of the bone marrow-biopsy specimen (Figure 1) revealed markedly hypercellular marrow with a loss of normal elements. There were sheets of blasts, including larger cells with oval-to-irregular nuclei, fine chromatin, distinct nucleoli, and scant cytoplasm, as well as more mature-appearing lymphocyte-like blasts with more condensed chromatin. Cytogenetic analysis revealed an abnormal karyotype: 46,XY,t(9;22)(q34;q11.2)[15]/46,idem,t(2;12)(p13;p13),?del(10)(p13)[3]/46,idem,del(6)(p21),add(7)(p13)[2]. On next-generation sequencing, SNaPshot analysis identified a RUNX1 mutation, and gene fusion analysis was positive for BCR-ABL1 e13a2. A diagnosis of B-cell acute lymphoblastic leukemia with BCR-ABL1 was made.	
Dr. Anandappa: Induction chemotherapy with vincristine, doxorubicin, methotrexate, cytarabine, and prednisone was administered, along with dasatinib and intrathecal cytarabine, methotrexate, and hydrocortisone. One month later, examination of a bone marrow-biopsy specimen revealed 7% blasts. Treatment with blinatumomab was started, and dasatinib was continued.
Seven months before this presentation, examination of a bone marrow-biopsy specimen revealed a complete hematologic response. BCR-ABL1 was undetectable by means of reverse-transcriptase-polymerase-chain-reaction testing.
Five months before this presentation, the patient underwent allogeneic hematopoietic-cell transplantation (HCT) from a matched, unrelated donor after myeloablative conditioning with cyclophosphamide and total-body irradiation. Early post-transplantation complications included severe mucositis and febrile neutropenia.
Two months before this presentation, examination of a bone marrow-biopsy specimen revealed a complete hematologic response, no BCR-ABL1 rearrangement, and full donor chimerism. Dasatinib was continued as maintenance therapy. During the next 2 months, the patient had worsening anemia, and dasatinib was stopped.
Two days before this presentation, the patient noticed ""large black blobs"" that looked like shadows in the periphery of the visual fields of both eyes. There were also intermittent episodes of blurry vision in both eyes that resolved after 10 minutes. Two days later, the patient sought an evaluation in the oncology clinic of this hospital and was transferred to the emergency department for further evaluation.
In the emergency department, the patient reported ongoing vision symptoms but no eye pain, flashing lights, or floaters. He also reported 3 weeks of night sweats, areas of swelling in the neck and groin, and a pruritic rash on the upper chest, upper back, and both arms. He had a history of chronic daily migraine headaches, which had frequently been associated with eye pain and photophobia but had not been associated with vision changes. Other medical history included depression and obesity. Medications included tacrolimus, trimethoprim-sulfamethoxazole, famciclovir, omeprazole, and escitalopram, as well as vitamin D and magnesium supplementation. There were no known drug allergies. The patient lived in a coastal town in New England with his mother. He had previously worked in the food-service industry. He had never smoked tobacco or used illicit drugs; he drank three cans of beer weekly. His family history included breast cancer and headaches in his maternal grandmother, prostate cancer in his paternal grandfather, and hypertension in his father.
On examination, the temperature was 36.9[degrees]C, the blood pressure 136/88 mm Hg, the pulse 104 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. Visual acuity was 20/25 in both eyes with correction, and visual fields were full on confrontation testing. The pupils were symmetric and reactive to light. There was no proptosis. Slit-lamp examination revealed few cells in the anterior chamber, and funduscopic examination was normal. Test results for cranial nerve function, strength, sensation, reflexes, coordination, and gait were normal. There was palpable lymphadenopathy in the cervical, clavicular, axillary, and inguinal regions. Discrete papules were present on both arms, and diffuse xerosis and an eczematous rash were present on the upper back and chest.
Laboratory testing revealed a platelet count of 47,000 per microliter (reference range, 150,000 to 400,000). Blood testing for cytomegalovirus, Epstein-Barr virus (EBV), varicella-zoster virus, and human herpesvirus 8 (HHV-8) DNA was negative. Screening for human immunodeficiency virus, syphilis, and Lyme disease was also negative. Examination of a peripheral-blood smear confirmed the presence of anemia and thrombocytopenia; there were no schistocytes. Additional laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Karen Rodriguez: Magnetic resonance imaging (MRI) of the head was performed. T2-weighted, fluid-attenuated inversion recovery images (Figure 2A and 2B) showed multiple new hyperintense lesions, measuring up to 11 mm in greatest dimension, within the supratentorial and infratentorial regions of the brain. Images obtained after the administration of contrast material showed faint enhancement of the lesions. These foci appeared to be centered within the juxtacortical and periventricular white matter and could reflect areas of demyelination, graft-versus-host disease (GVHD) involving the central nervous system (CNS), acute lymphoblastic leukemia with CNS involvement, or an infectious process. There was no abnormal enhancement of the optic nerves or the orbital structures.	
18F-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) and computed tomography (CT) was also performed. The PET-CT scans (Figure 2C through 2H) showed moderate-to-intense FDG uptake associated with widespread lymphadenopathy, including bilateral cervical, axillary, external iliac, and inguinal lymph nodes. There was also abnormal uptake in the spleen.
Dr. Anandappa: The patient was admitted to this hospital, and lumbar puncture was performed. Cerebrospinal fluid analysis revealed a total protein level of 147 mg per deciliter (reference range, 5 to 55) and a glucose level of 49 mg per deciliter (2.7 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]). The white-cell count was 21 per microliter (reference range, 0 to 5), with 61% lymphocytes, 27% neutrophils, and 3% eosinophils; the red-cell count was 16,000 per microliter (reference range, 0 to 5), with xanthochromia present. Gram's staining of cerebrospinal fluid showed a moderate amount of mononuclear cells and no organisms. Cytologic studies were notable for increased lymphocytes and plasma cells. A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 25-year-old man with a history of B-cell acute lymphoblastic leukemia was evaluated in the emergency department of this hospital because of vision changes.
Ten months before this presentation, the patient was evaluated for fatigue and dyspnea on exertion. Laboratory testing revealed a hemoglobin level of 3.5 g per deciliter (reference range, 13.5 to 17.5) and a white-cell count of 23,450 per microliter (reference range, 4000 to 11,000), with 81% lymphocytes and 4% blasts. A bone marrow biopsy was performed.
Dr. Judith A. Ferry: Examination of the bone marrow-biopsy specimen (Figure 1) revealed markedly hypercellular marrow with a loss of normal elements. There were sheets of blasts, including larger cells with oval-to-irregular nuclei, fine chromatin, distinct nucleoli, and scant cytoplasm, as well as more mature-appearing lymphocyte-like blasts with more condensed chromatin. Cytogenetic analysis revealed an abnormal karyotype: 46,XY,t(9;22)(q34;q11.2)[15]/46,idem,t(2;12)(p13;p13),?del(10)(p13)[3]/46,idem,del(6)(p21),add(7)(p13)[2]. On next-generation sequencing, SNaPshot analysis identified a RUNX1 mutation, and gene fusion analysis was positive for BCR-ABL1 e13a2. A diagnosis of B-cell acute lymphoblastic leukemia with BCR-ABL1 was made.	
Dr. Anandappa: Induction chemotherapy with vincristine, doxorubicin, methotrexate, cytarabine, and prednisone was administered, along with dasatinib and intrathecal cytarabine, methotrexate, and hydrocortisone. One month later, examination of a bone marrow-biopsy specimen revealed 7% blasts. Treatment with blinatumomab was started, and dasatinib was continued.
Seven months before this presentation, examination of a bone marrow-biopsy specimen revealed a complete hematologic response. BCR-ABL1 was undetectable by means of reverse-transcriptase-polymerase-chain-reaction testing.
Five months before this presentation, the patient underwent allogeneic hematopoietic-cell transplantation (HCT) from a matched, unrelated donor after myeloablative conditioning with cyclophosphamide and total-body irradiation. Early post-transplantation complications included severe mucositis and febrile neutropenia.
Two months before this presentation, examination of a bone marrow-biopsy specimen revealed a complete hematologic response, no BCR-ABL1 rearrangement, and full donor chimerism. Dasatinib was continued as maintenance therapy. During the next 2 months, the patient had worsening anemia, and dasatinib was stopped.
Two days before this presentation, the patient noticed ""large black blobs"" that looked like shadows in the periphery of the visual fields of both eyes. There were also intermittent episodes of blurry vision in both eyes that resolved after 10 minutes. Two days later, the patient sought an evaluation in the oncology clinic of this hospital and was transferred to the emergency department for further evaluation.
In the emergency department, the patient reported ongoing vision symptoms but no eye pain, flashing lights, or floaters. He also reported 3 weeks of night sweats, areas of swelling in the neck and groin, and a pruritic rash on the upper chest, upper back, and both arms. He had a history of chronic daily migraine headaches, which had frequently been associated with eye pain and photophobia but had not been associated with vision changes. Other medical history included depression and obesity. Medications included tacrolimus, trimethoprim-sulfamethoxazole, famciclovir, omeprazole, and escitalopram, as well as vitamin D and magnesium supplementation. There were no known drug allergies. The patient lived in a coastal town in New England with his mother. He had previously worked in the food-service industry. He had never smoked tobacco or used illicit drugs; he drank three cans of beer weekly. His family history included breast cancer and headaches in his maternal grandmother, prostate cancer in his paternal grandfather, and hypertension in his father.
On examination, the temperature was 36.9[degrees]C, the blood pressure 136/88 mm Hg, the pulse 104 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. Visual acuity was 20/25 in both eyes with correction, and visual fields were full on confrontation testing. The pupils were symmetric and reactive to light. There was no proptosis. Slit-lamp examination revealed few cells in the anterior chamber, and funduscopic examination was normal. Test results for cranial nerve function, strength, sensation, reflexes, coordination, and gait were normal. There was palpable lymphadenopathy in the cervical, clavicular, axillary, and inguinal regions. Discrete papules were present on both arms, and diffuse xerosis and an eczematous rash were present on the upper back and chest.
Laboratory testing revealed a platelet count of 47,000 per microliter (reference range, 150,000 to 400,000). Blood testing for cytomegalovirus, Epstein-Barr virus (EBV), varicella-zoster virus, and human herpesvirus 8 (HHV-8) DNA was negative. Screening for human immunodeficiency virus, syphilis, and Lyme disease was also negative. Examination of a peripheral-blood smear confirmed the presence of anemia and thrombocytopenia; there were no schistocytes. Additional laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Karen Rodriguez: Magnetic resonance imaging (MRI) of the head was performed. T2-weighted, fluid-attenuated inversion recovery images (Figure 2A and 2B) showed multiple new hyperintense lesions, measuring up to 11 mm in greatest dimension, within the supratentorial and infratentorial regions of the brain. Images obtained after the administration of contrast material showed faint enhancement of the lesions. These foci appeared to be centered within the juxtacortical and periventricular white matter and could reflect areas of demyelination, graft-versus-host disease (GVHD) involving the central nervous system (CNS), acute lymphoblastic leukemia with CNS involvement, or an infectious process. There was no abnormal enhancement of the optic nerves or the orbital structures.	
18F-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) and computed tomography (CT) was also performed. The PET-CT scans (Figure 2C through 2H) showed moderate-to-intense FDG uptake associated with widespread lymphadenopathy, including bilateral cervical, axillary, external iliac, and inguinal lymph nodes. There was also abnormal uptake in the spleen.
Dr. Anandappa: The patient was admitted to this hospital, and lumbar puncture was performed. Cerebrospinal fluid analysis revealed a total protein level of 147 mg per deciliter (reference range, 5 to 55) and a glucose level of 49 mg per deciliter (2.7 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]). The white-cell count was 21 per microliter (reference range, 0 to 5), with 61% lymphocytes, 27% neutrophils, and 3% eosinophils; the red-cell count was 16,000 per microliter (reference range, 0 to 5), with xanthochromia present. Gram's staining of cerebrospinal fluid showed a moderate amount of mononuclear cells and no organisms. Cytologic studies were notable for increased lymphocytes and plasma cells. A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Post-transplant lymphoproliferative disorder (PTLD). The patient's history of B-cell acute lymphoblastic leukemia and subsequent allogeneic hematopoietic-cell transplantation, along with symptoms of vision changes, night sweats, lymphadenopathy, and a pruritic rash, suggest a post-transplant complication. The MRI findings of multiple new hyperintense lesions in the brain could be indicative of CNS involvement in a disease process. The PET-CT scans showing FDG uptake associated with widespread lymphadenopathy and in the spleen further suggest a lymphoproliferative disorder. The cerebrospinal fluid analysis revealing increased lymphocytes and plasma cells also supports this diagnosis. PTLD is a known potential complication following transplantation, particularly in patients who have received immunosuppressive therapy.""
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        ""content"": ""The patient is a 25-year-old male with a history of B-cell acute lymphoblastic leukemia who presents with vision changes, night sweats, lymphadenopathy, and a pruritic rash. The differential diagnosis for this patient includes relapse of his leukemia, central nervous system (CNS) involvement of his leukemia, graft-versus-host disease (GVHD), and an infectious process. The patient's history of B-cell acute lymphoblastic leukemia and recent allogeneic hematopoietic-cell transplantation (HCT) are significant and guide the differential diagnosis. The patient's vision changes and MRI findings could suggest CNS involvement of his leukemia, but could also be due to GVHD or an infectious process. The patient's night sweats, lymphadenopathy, and rash could also be due to a relapse of his leukemia or GVHD. The patient's recent HCT makes GVHD a strong possibility. The patient's laboratory findings of anemia and thrombocytopenia could be due to bone marrow suppression from his leukemia or from GVHD. The patient's negative infectious disease workup makes an infectious process less likely. The patient's PET-CT findings of FDG uptake associated with widespread lymphadenopathy and in the spleen could be due to a relapse of his leukemia or GVHD. The patient's cerebrospinal fluid findings of increased lymphocytes and plasma cells could suggest CNS involvement of his leukemia, but could also be due to GVHD. Given the patient's history of B-cell acute lymphoblastic leukemia, recent HCT, and the constellation of his symptoms and findings, GVHD is the most likely diagnosis.\n\nDiagnosis: Graft-versus-host disease (GVHD)""
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10.1056/NEJMcpc2201231,Case 19-2022: A 29-Year-Old Woman with Jaundice and Chronic Diarrhea,"Hemoglobin (g/dl) 11.9–15.5 13.6 13.2
Hematocrit (%) 35.6–45.5 39.8 37.9
White-cell count (per μl) 4500–10,700 8290 7870
Differential count (per μl)
Neutrophils   6209 —
Lymphocytes   1509 —
Monocytes   431 —
Eosinophils   912 —
Basophils  00 332 —
Platelet count (per μl) 140,00 ,000 228,000 233,000
Sodium (mmol/liter)   139 141
Potassium (mmol/liter)   3.6 4.5
Chloride (mmol/liter) 98–107 98 103
Carbon dioxide (mmol/liter) 22. 9.0 25.8 25
Urea nitrogen (mg/dl) 6–20 9 10
Creatinine (mg/dl) 0.57–1.00 0.80 0.76
Glucose (mg/dl) 6 9 162 124
Calcium (mg/dl) 8.6–10.5 10.0 —
Lipase (U/liter) 13–60 72 —
Alanine aminotransferase (U/liter) 1–33 327 85
Aspartate aminotransferase (U/liter) 1–32 104 267
Alkaline phosphatase (U/liter) 39–117 172 150
Total bilirubin (mg/dl) 0.1–1.2 5.8 6.7
Globulin (g/dl)   3.4 —
Albumin (g/dl) 3.50–5.20 4.10 —
Carbohydrate antigen 19-9 (U/ml)  5 73 79",Pancreatic ductal adenocarcinoma,Exocrine pancreatic cancer (pancreatic ductal adenocarcinoma).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-year-old woman was evaluated in the gastroenterology clinic of this hospital for the management of a soft-tissue mass in the head of the pancreas.
The patient had been well until 7 weeks before this presentation, when progressive pruritus throughout the body developed, along with nausea, bloating, and watery mustard-colored diarrhea. She had eaten sushi for dinner the previous night. She was evaluated in an urgent care clinic in the southeastern United States; she had recently moved there from New England. An injection of methylprednisolone was administered, and hydroxyzine and diphenoxylate-atropine were prescribed. During the next 3 weeks, the symptoms did not abate and jaundice developed, along with new discomfort in the right upper quadrant of the abdomen, decreased appetite, and amber-colored urine.
Four weeks before this presentation, the patient was evaluated in the emergency department of a local hospital. The alanine aminotransferase level was 327 U per liter (reference range, 1 to 33), the aspartate aminotransferase level 104 U per liter (reference range, 1 to 32), and the total bilirubin level 5.8 mg per deciliter (reference range, 0.1 to 1.2). The carbohydrate antigen 19-9 (CA 19-9) level was 73 U per milliliter (reference range, 0 to 35). Additional laboratory test results are shown in Table 1. Imaging studies were obtained.	

Computed tomography (CT) of the abdomen, performed after the intravenous administration of contrast material, reportedly revealed a distended gallbladder with sludge, as well as dilated hepatic and pancreatic ducts. The patient was admitted to the local hospital. On the second hospital day, results of liver-function tests improved, and she was discharged home with plans for an outpatient evaluation with a gastroenterologist.
However, the next day, the patient flew back to New England and presented to the emergency department of a second hospital for further evaluation. On evaluation, she described persistent diffuse pruritus, nausea, right upper abdominal pain, and mustard-colored diarrhea. She also reported fatigue, unintentional weight loss of 3.2 kg during the past month, and poor sleep.
The patient had a history of anxiety and depression. She took no medications and had no known drug allergies. Aside from her recent move to the southeastern United States and trip back to New England, there was no recent travel. She worked seasonally as an official at sporting events. She smoked cigarettes occasionally, drank alcohol rarely, and did not use illicit drugs. Her family history included colon cancer in her maternal grandmother, maternal grandfather, and paternal grandmother; breast cancer in her maternal aunt and paternal aunt; and thyroid cancer in her father. In addition, her maternal grandmother had diabetes, and both grandmothers had coronary artery disease.
On examination, the temperature was 36.9[degrees]C, the blood pressure 155/82 mm Hg, the pulse 94 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She was thin and appeared jaundiced, with scleral icterus. She had diffuse excoriations from scratching. The bowel sounds were normal. There was mild tenderness in the right upper abdomen on palpation, but masses and hepatosplenomegaly were not detected. The remainder of the examination was normal.
The alanine aminotransferase level was 85 U per liter, the aspartate aminotransferase level 267 U per liter, and the total bilirubin level 6.7 mg per deciliter. The CA 19-9 level was 79 U per milliliter. Additional laboratory test results are shown in Table 1. The abdominal CT images obtained at the first hospital were reviewed, and additional imaging studies were obtained.
Dr. Avinash Kambadakone: CT of the abdomen (Figure 1A and 1B), performed after the intravenous administration of contrast material, revealed diffuse dilatation of the intrahepatic and extrahepatic biliary ducts, as well as dilatation of the pancreatic ducts. The dilated ducts terminated abruptly in the pancreatic head. There was a hypodense pancreatic mass at the site of duct obstruction. Magnetic resonance cholangiopancreatography (Figure 1C and 1D) also revealed dilatation of the biliary and pancreatic ducts, which narrowed abruptly at the level of the pancreatic head, with a heterogeneously enhancing mass at the site of obstruction.	
Figure 1 Figure 1
Dr. DuBois: The patient was admitted to the second hospital. Endoscopic retrograde cholangiopancreatography revealed a stricture in the bile duct at the level of the mass, and a stent was placed. The bilirubin level initially decreased, but pruritus and diarrhea persisted. By the seventh hospital day, the bilirubin level had increased to 12.6 mg per deciliter and the CA 19-9 level had increased to 959 U per milliliter. Additional diagnostic testing was performed.
Dr. Kambadakone: Endoscopic ultrasonography (Figure 1E) revealed a hypoechoic mass in the pancreatic head. Fine-needle aspiration was performed.
Dr. DuBois: The aspirate showed variably atypical epithelium, but the quantity and quality of the findings were insufficient for definitive diagnosis. Given the uncertain diagnosis and the possibility of cancer, a surgical consultation was obtained. Surgical removal of the mass was recommended to establish the definitive diagnosis, but the patient declined surgery. Prednisone was administered, and the pruritus and diarrhea abated. On the 20th hospital day, the patient was discharged with plans for an outpatient follow-up evaluation with a gastroenterologist.
Three days after discharge from the second hospital, the patient was evaluated in the gastroenterology clinic of this hospital. At that time, her symptoms had resolved, the results of liver-function tests were normal, and the CA 19-9 level had decreased to 80 U per milliliter. IgG levels (total and subclasses) were normal, and tests for antinuclear antibodies (ANA) were negative. The possibility of cancer was explained to the patient, and surgical removal of the mass was again recommended, but the patient declined surgery owing to multiple issues related to her work and personal life. A management plan that was acceptable to the patient was adopted during the next 6 months. The patient was closely monitored, and biliary stents were changed when they became occluded. Additional diagnostic procedures were performed, and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-year-old woman was evaluated in the gastroenterology clinic of this hospital for the management of a soft-tissue mass in the head of the pancreas.
The patient had been well until 7 weeks before this presentation, when progressive pruritus throughout the body developed, along with nausea, bloating, and watery mustard-colored diarrhea. She had eaten sushi for dinner the previous night. She was evaluated in an urgent care clinic in the southeastern United States; she had recently moved there from New England. An injection of methylprednisolone was administered, and hydroxyzine and diphenoxylate-atropine were prescribed. During the next 3 weeks, the symptoms did not abate and jaundice developed, along with new discomfort in the right upper quadrant of the abdomen, decreased appetite, and amber-colored urine.
Four weeks before this presentation, the patient was evaluated in the emergency department of a local hospital. The alanine aminotransferase level was 327 U per liter (reference range, 1 to 33), the aspartate aminotransferase level 104 U per liter (reference range, 1 to 32), and the total bilirubin level 5.8 mg per deciliter (reference range, 0.1 to 1.2). The carbohydrate antigen 19-9 (CA 19-9) level was 73 U per milliliter (reference range, 0 to 35). Additional laboratory test results are shown in Table 1. Imaging studies were obtained.	

Computed tomography (CT) of the abdomen, performed after the intravenous administration of contrast material, reportedly revealed a distended gallbladder with sludge, as well as dilated hepatic and pancreatic ducts. The patient was admitted to the local hospital. On the second hospital day, results of liver-function tests improved, and she was discharged home with plans for an outpatient evaluation with a gastroenterologist.
However, the next day, the patient flew back to New England and presented to the emergency department of a second hospital for further evaluation. On evaluation, she described persistent diffuse pruritus, nausea, right upper abdominal pain, and mustard-colored diarrhea. She also reported fatigue, unintentional weight loss of 3.2 kg during the past month, and poor sleep.
The patient had a history of anxiety and depression. She took no medications and had no known drug allergies. Aside from her recent move to the southeastern United States and trip back to New England, there was no recent travel. She worked seasonally as an official at sporting events. She smoked cigarettes occasionally, drank alcohol rarely, and did not use illicit drugs. Her family history included colon cancer in her maternal grandmother, maternal grandfather, and paternal grandmother; breast cancer in her maternal aunt and paternal aunt; and thyroid cancer in her father. In addition, her maternal grandmother had diabetes, and both grandmothers had coronary artery disease.
On examination, the temperature was 36.9[degrees]C, the blood pressure 155/82 mm Hg, the pulse 94 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She was thin and appeared jaundiced, with scleral icterus. She had diffuse excoriations from scratching. The bowel sounds were normal. There was mild tenderness in the right upper abdomen on palpation, but masses and hepatosplenomegaly were not detected. The remainder of the examination was normal.
The alanine aminotransferase level was 85 U per liter, the aspartate aminotransferase level 267 U per liter, and the total bilirubin level 6.7 mg per deciliter. The CA 19-9 level was 79 U per milliliter. Additional laboratory test results are shown in Table 1. The abdominal CT images obtained at the first hospital were reviewed, and additional imaging studies were obtained.
Dr. Avinash Kambadakone: CT of the abdomen (Figure 1A and 1B), performed after the intravenous administration of contrast material, revealed diffuse dilatation of the intrahepatic and extrahepatic biliary ducts, as well as dilatation of the pancreatic ducts. The dilated ducts terminated abruptly in the pancreatic head. There was a hypodense pancreatic mass at the site of duct obstruction. Magnetic resonance cholangiopancreatography (Figure 1C and 1D) also revealed dilatation of the biliary and pancreatic ducts, which narrowed abruptly at the level of the pancreatic head, with a heterogeneously enhancing mass at the site of obstruction.	
Figure 1 Figure 1
Dr. DuBois: The patient was admitted to the second hospital. Endoscopic retrograde cholangiopancreatography revealed a stricture in the bile duct at the level of the mass, and a stent was placed. The bilirubin level initially decreased, but pruritus and diarrhea persisted. By the seventh hospital day, the bilirubin level had increased to 12.6 mg per deciliter and the CA 19-9 level had increased to 959 U per milliliter. Additional diagnostic testing was performed.
Dr. Kambadakone: Endoscopic ultrasonography (Figure 1E) revealed a hypoechoic mass in the pancreatic head. Fine-needle aspiration was performed.
Dr. DuBois: The aspirate showed variably atypical epithelium, but the quantity and quality of the findings were insufficient for definitive diagnosis. Given the uncertain diagnosis and the possibility of cancer, a surgical consultation was obtained. Surgical removal of the mass was recommended to establish the definitive diagnosis, but the patient declined surgery. Prednisone was administered, and the pruritus and diarrhea abated. On the 20th hospital day, the patient was discharged with plans for an outpatient follow-up evaluation with a gastroenterologist.
Three days after discharge from the second hospital, the patient was evaluated in the gastroenterology clinic of this hospital. At that time, her symptoms had resolved, the results of liver-function tests were normal, and the CA 19-9 level had decreased to 80 U per milliliter. IgG levels (total and subclasses) were normal, and tests for antinuclear antibodies (ANA) were negative. The possibility of cancer was explained to the patient, and surgical removal of the mass was again recommended, but the patient declined surgery owing to multiple issues related to her work and personal life. A management plan that was acceptable to the patient was adopted during the next 6 months. The patient was closely monitored, and biliary stents were changed when they became occluded. Additional diagnostic procedures were performed, and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 29-year-old woman presenting with pruritus, nausea, bloating, watery mustard-colored diarrhea, jaundice, right upper abdominal pain, fatigue, unintentional weight loss, and poor sleep. She also has a history of anxiety and depression. The patient has a family history of colon cancer, breast cancer, thyroid cancer, diabetes, and coronary artery disease. The patient's lab results show elevated levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin. The carbohydrate antigen 19-9 (CA 19-9) level is also elevated. Imaging studies reveal a distended gallbladder with sludge, dilated hepatic and pancreatic ducts, and a hypodense pancreatic mass at the site of duct obstruction. \n\nThe differential diagnosis for this patient includes pancreatic cancer, cholangiocarcinoma, and autoimmune pancreatitis. The patient's elevated CA 19-9 level, the presence of a pancreatic mass, and her family history of various cancers make pancreatic cancer a strong possibility. However, the patient's symptoms and lab results could also be consistent with cholangiocarcinoma, a cancer that forms in the bile ducts. Autoimmune pancreatitis could also present with similar symptoms and lab results, but the patient's normal IgG levels and negative ANA test make this less likely.\n\nThe patient's symptoms improved with the administration of prednisone, which could suggest an autoimmune process. However, the patient's persistent pancreatic mass and elevated CA 19-9 level are concerning for malignancy. Given the patient's refusal of surgery, a definitive diagnosis cannot be made. However, based on the available information, the most likely diagnosis is pancreatic cancer.""
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10.1056/NEJMcpc2107348,Case 18-2022: A 29-Year-Old Woman with Recurrent Fractures,"Sodium (mmol/liter)   137   138
Potassium (mmol/liter) 3.6–5.1 4.2   4.2
Chloride (mmol/liter) 98–107 101   99
Carbon dioxide (mmol/liter) 22–32 27   25
Urea nitrogen (mg/dl) 6–20 15   15
Creatinine (mg/dl) 0.40–1.00 0.58   0.51
Albumin (g/dl)   —   4.9
Calcium (mg/dl) 8.9–10.3 9.5   9.7
Magnesium (mg/dl) — —   2.1
Phosphorus (mg/dl) — —   1.0
25-Hydroxyvitamin D (ng/ml) 2 0 26 2 0 22
1,25-Dihydroxyvitamin D (pg/ml) — — 18–78 11
Parathyroid hormone (pg/ml) 15–79 45   41
Cortisol (μg/dl) 2.5–19.5 6.3 — —
Thyrotropin (μIU/ml) — — 0.4 0 5.79
Free thyroxine (ng/dl) — — 0.9–1.8 1.2
Total triiodothyronine (ng/dl) — — 60–181 182
Alanine aminotransferase (U/liter) — —   37
Aspartate aminotransferase (U/liter) — —   21
Alkaline phosphatase (U/liter) — —   261
White-cell count (per μl) — —   6560
Erythrocyte sedimentation rate (mm/hr) — —  0 22",Phosphaturic mesenchymal tumor causing osteomalacia,Tumor-induced osteomalacia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-year-old woman was admitted to this hospital because of recurrent bone fractures and hypophosphatemia.
The patient had been well until 19 months before admission, when pain in the right midfoot developed during a vacation in Europe. On her return to the United States, she was evaluated by her primary care physician at a clinic affiliated with another hospital; an orthotic device was recommended, but the foot pain did not decrease with use of the device.
Three months later, the pain in the right foot increased in severity after a second vacation in Europe. Radiography of the right foot reportedly revealed no fracture; physical therapy was recommended. During the subsequent 8 months, the pain continued to gradually increase in severity, was worse when the patient stood upright or walked, and was relieved with the administration of ibuprofen.
Eight months before admission, the patient tripped, and the severity of pain in the right foot increased suddenly. She was evaluated in the orthopedic clinic of this hospital. On examination, the height was 173 cm, the weight 115 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 38.6. There was tenderness over the right third metatarsal. Imaging studies were obtained.
Dr. Rene Balza: Radiography of the right foot (Figure 1A) revealed a fracture of the third metatarsal shaft. Magnetic resonance imaging (MRI) of the right foot revealed a nondisplaced, incompletely healed transverse fracture of the third metatarsal shaft, as well as subchondral sclerosis and bone marrow edema within the distal navicular bone and in the calcaneocuboid joint. Bone stimulation was recommended, but the patient's pain did not abate after these treatments.	

Dr. Selen: Seven months before admission, the patient had increased pain in the right foot after a fall while walking on ice. Additional imaging studies were obtained.
Dr. Balza: Radiography of the right foot (Figure 1B) revealed fractures of the distal fourth and fifth metatarsals.
Dr. Selen: Five months before admission, the second metatarsal region of the right foot was tender on palpation after the patient had walked up a flight of stairs. However, no evidence of a fracture was seen on radiography.
Four months before admission, the patient was evaluated in the endocrinology clinic affiliated with the other hospital. The calcium level was 9.5 mg per deciliter (2.4 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter [2.1 to 2.6 mmol per liter]), the 25-hydroxyvitamin D level 26 ng per milliliter (65 nmol per liter; reference range, 20 to 80 ng per deciliter [50 to 200 nmol per liter]), and the parathyroid hormone level 45 pg per milliliter (reference range, 10 to 60); other laboratory test results are shown in Table 1. Dual-energy x-ray absorptiometry, performed for the assessment of bone mineral density, revealed normal bone mass in the lumbar spine (z score, 0.0; reference range, 1.9 to -1.9) and in the femoral neck (z score, 0.4; reference range, 1.9 to -1.9). Calcium and vitamin D supplementation and weight loss were recommended. The pain in the right foot persisted, and additional imaging studies were obtained.	

Dr. Balza: Three months before admission, MRI of the right foot (Figure 1C and 1D) showed a nondisplaced fracture of the second metatarsal metadiaphysis with associated bone and soft-tissue edema, a nondisplaced fracture of the medial cuneiform, and healing fractures of the third, fourth, and fifth metatarsals. A controlled ankle motion walking boot and crutches were recommended for ambulation.
Dr. Selen: During the next 3 months, the pain in the right foot persisted, and new pain developed in the left foot. The patient was seen in the pain medicine and podiatry clinics affiliated with the other hospital. Diagnoses of plantar fasciitis, Achilles' tendinitis, and sinus tarsi syndrome were considered. Treatment with methylprednisolone and celecoxib was initiated, and the patient was referred to the rheumatology clinic of this hospital.
On evaluation in the rheumatology clinic, the patient reported bilateral foot and ankle pain and swelling that was greater in the right foot and ankle than in the left, as well as stiffness and warmth in the ankles. There was lower back pain and bilateral hip pain, which was greater on the right side than on the left side. The patient reported that the back and hip pain had been present since she was a teenager but had gradually increased in severity during the previous year. Fatigue and generalized weakness had developed and worsened during the previous month. There was no fever, weight loss, or change in diet.
Menarche had occurred when the patient was 11 years of age, and menstrual cycles had been regular since then. There was a history of fractures of the left wrist in childhood. Other medical history included obesity, hyperlipidemia, anxiety, nephrolithiasis, biliary dyskinesia (which had led to cholecystectomy 1 year before this admission), and nonalcoholic fatty liver disease diagnosed on the basis of a liver biopsy. Medications included celecoxib, ergocalciferol, citalopram, and lorazepam; she had no known drug allergies. The patient lived alone in a suburban area of New England and had previously worked as a nurse; however, she was unable to work during the previous 8 months because of pain and difficulty with ambulation. She did not smoke cigarettes, drink alcohol, or use illicit drugs. Her mother had osteopenia; her mother, father, and sister had psoriasis; her father had psoriatic arthritis; and her brother had the Williams syndrome, a rare genetic and developmental disorder.
On examination, the temperature was 36.9[degrees]C, the blood pressure 121/78, and the heart rate 94 beats per minute. Dentition was normal, and the gait was antalgic. Proximal muscle strength was intact in both arms (5/5) and slightly reduced in the legs (4/5). There was tenderness over the lumbar spine and sacroiliac joints that was more pronounced on the right side than on the left side. The FABER test - in which the leg is flexed and the thigh is abducted and externally rotated - elicited pain in both hips. There was tenderness over the right midfoot and warmth and swelling of the ankles. No musculoskeletal deformities, bowing of the legs, lymphadenopathy, skin lesions, or rashes were noted. The blood level of phosphorus was 1.0 mg per deciliter (0.3 mmol per liter; reference range, 2.6 to 4.5 mg per deciliter [0.8 to 1.5 mmol per liter]); other laboratory test results are shown in Table 1. The patient was instructed to go to the emergency department of this hospital. Intravenous sodium phosphate and oral potassium phosphate were administered. Additional imaging studies were obtained.
Dr. Balza: Radiography of the lumbar spine, pelvis, hips, and ankles revealed anterolisthesis of L4 and L5 with a defect in the pars interarticularis; there were no fractures. On radiography of the right foot, a fracture in the third metatarsal was initially identified 8 months before admission (Figure 1A), followed by the development of fractures in the fourth and fifth metatarsals 1 month later (Figure 1B). Subsequently, T2-weighted MRI of the sacrum with fat suppression performed on admission (Figure 1E and 1F) revealed vertically oriented hypointense bands in the bilateral sacral alae and a horizontally oriented hypointense band in S2, as well as bone marrow edema adjacent to the fracture lines; the combination of these findings was consistent with an H-shaped sacral insufficiency fracture.
Dr. Selen: The patient was admitted to the hospital. A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-year-old woman was admitted to this hospital because of recurrent bone fractures and hypophosphatemia.
The patient had been well until 19 months before admission, when pain in the right midfoot developed during a vacation in Europe. On her return to the United States, she was evaluated by her primary care physician at a clinic affiliated with another hospital; an orthotic device was recommended, but the foot pain did not decrease with use of the device.
Three months later, the pain in the right foot increased in severity after a second vacation in Europe. Radiography of the right foot reportedly revealed no fracture; physical therapy was recommended. During the subsequent 8 months, the pain continued to gradually increase in severity, was worse when the patient stood upright or walked, and was relieved with the administration of ibuprofen.
Eight months before admission, the patient tripped, and the severity of pain in the right foot increased suddenly. She was evaluated in the orthopedic clinic of this hospital. On examination, the height was 173 cm, the weight 115 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 38.6. There was tenderness over the right third metatarsal. Imaging studies were obtained.
Dr. Rene Balza: Radiography of the right foot (Figure 1A) revealed a fracture of the third metatarsal shaft. Magnetic resonance imaging (MRI) of the right foot revealed a nondisplaced, incompletely healed transverse fracture of the third metatarsal shaft, as well as subchondral sclerosis and bone marrow edema within the distal navicular bone and in the calcaneocuboid joint. Bone stimulation was recommended, but the patient's pain did not abate after these treatments.	

Dr. Selen: Seven months before admission, the patient had increased pain in the right foot after a fall while walking on ice. Additional imaging studies were obtained.
Dr. Balza: Radiography of the right foot (Figure 1B) revealed fractures of the distal fourth and fifth metatarsals.
Dr. Selen: Five months before admission, the second metatarsal region of the right foot was tender on palpation after the patient had walked up a flight of stairs. However, no evidence of a fracture was seen on radiography.
Four months before admission, the patient was evaluated in the endocrinology clinic affiliated with the other hospital. The calcium level was 9.5 mg per deciliter (2.4 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter [2.1 to 2.6 mmol per liter]), the 25-hydroxyvitamin D level 26 ng per milliliter (65 nmol per liter; reference range, 20 to 80 ng per deciliter [50 to 200 nmol per liter]), and the parathyroid hormone level 45 pg per milliliter (reference range, 10 to 60); other laboratory test results are shown in Table 1. Dual-energy x-ray absorptiometry, performed for the assessment of bone mineral density, revealed normal bone mass in the lumbar spine (z score, 0.0; reference range, 1.9 to -1.9) and in the femoral neck (z score, 0.4; reference range, 1.9 to -1.9). Calcium and vitamin D supplementation and weight loss were recommended. The pain in the right foot persisted, and additional imaging studies were obtained.	

Dr. Balza: Three months before admission, MRI of the right foot (Figure 1C and 1D) showed a nondisplaced fracture of the second metatarsal metadiaphysis with associated bone and soft-tissue edema, a nondisplaced fracture of the medial cuneiform, and healing fractures of the third, fourth, and fifth metatarsals. A controlled ankle motion walking boot and crutches were recommended for ambulation.
Dr. Selen: During the next 3 months, the pain in the right foot persisted, and new pain developed in the left foot. The patient was seen in the pain medicine and podiatry clinics affiliated with the other hospital. Diagnoses of plantar fasciitis, Achilles' tendinitis, and sinus tarsi syndrome were considered. Treatment with methylprednisolone and celecoxib was initiated, and the patient was referred to the rheumatology clinic of this hospital.
On evaluation in the rheumatology clinic, the patient reported bilateral foot and ankle pain and swelling that was greater in the right foot and ankle than in the left, as well as stiffness and warmth in the ankles. There was lower back pain and bilateral hip pain, which was greater on the right side than on the left side. The patient reported that the back and hip pain had been present since she was a teenager but had gradually increased in severity during the previous year. Fatigue and generalized weakness had developed and worsened during the previous month. There was no fever, weight loss, or change in diet.
Menarche had occurred when the patient was 11 years of age, and menstrual cycles had been regular since then. There was a history of fractures of the left wrist in childhood. Other medical history included obesity, hyperlipidemia, anxiety, nephrolithiasis, biliary dyskinesia (which had led to cholecystectomy 1 year before this admission), and nonalcoholic fatty liver disease diagnosed on the basis of a liver biopsy. Medications included celecoxib, ergocalciferol, citalopram, and lorazepam; she had no known drug allergies. The patient lived alone in a suburban area of New England and had previously worked as a nurse; however, she was unable to work during the previous 8 months because of pain and difficulty with ambulation. She did not smoke cigarettes, drink alcohol, or use illicit drugs. Her mother had osteopenia; her mother, father, and sister had psoriasis; her father had psoriatic arthritis; and her brother had the Williams syndrome, a rare genetic and developmental disorder.
On examination, the temperature was 36.9[degrees]C, the blood pressure 121/78, and the heart rate 94 beats per minute. Dentition was normal, and the gait was antalgic. Proximal muscle strength was intact in both arms (5/5) and slightly reduced in the legs (4/5). There was tenderness over the lumbar spine and sacroiliac joints that was more pronounced on the right side than on the left side. The FABER test - in which the leg is flexed and the thigh is abducted and externally rotated - elicited pain in both hips. There was tenderness over the right midfoot and warmth and swelling of the ankles. No musculoskeletal deformities, bowing of the legs, lymphadenopathy, skin lesions, or rashes were noted. The blood level of phosphorus was 1.0 mg per deciliter (0.3 mmol per liter; reference range, 2.6 to 4.5 mg per deciliter [0.8 to 1.5 mmol per liter]); other laboratory test results are shown in Table 1. The patient was instructed to go to the emergency department of this hospital. Intravenous sodium phosphate and oral potassium phosphate were administered. Additional imaging studies were obtained.
Dr. Balza: Radiography of the lumbar spine, pelvis, hips, and ankles revealed anterolisthesis of L4 and L5 with a defect in the pars interarticularis; there were no fractures. On radiography of the right foot, a fracture in the third metatarsal was initially identified 8 months before admission (Figure 1A), followed by the development of fractures in the fourth and fifth metatarsals 1 month later (Figure 1B). Subsequently, T2-weighted MRI of the sacrum with fat suppression performed on admission (Figure 1E and 1F) revealed vertically oriented hypointense bands in the bilateral sacral alae and a horizontally oriented hypointense band in S2, as well as bone marrow edema adjacent to the fracture lines; the combination of these findings was consistent with an H-shaped sacral insufficiency fracture.
Dr. Selen: The patient was admitted to the hospital. A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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10.1056/NEJMcpc2115849,"Case 16-2022: A 55-Year-Old Man with Fevers, Night Sweats, and a Mediastinal Mass","Hemoglobin (g/dl) 13.0–17.4 14.4 12.5   9.4
Hematocrit (%) 38.0–50.0 41.4 36.1   29.0
Platelet count (per μl)   180,000 165,000   93,000
White-cell count (per μl)  9500 15,100   9120
Differential count (per μl)
Neutrophils 2400–7600 8060 13,170   7060
Lymphocytes 100 300 790 750   1030
Monocytes 25  630 1160   840
Eosinophils  0 0 0   70
Reticulocytes (%) — — — 0.5–2.5 2.2
Sodium (mmol/liter)   137 139   139
Potassium (mmol/liter) 3.3–5.3 4.3 4.9   4.8
Chloride (mmol/liter)   104 110   105
Carbon dioxide (mmol/liter) 21–30 20 18   20
Urea nitrogen (mg/dl) 6–19 32 37   41
Creatinine (mg/dl) 0.50–1.30 1.32 1.64   1.62
Calcium (mg/dl) 8.6–10.4 8.9 8.2   8.0
Glucose (mg/dl) 70–99 156 126   110
N-terminal pro–B-type natriuretic peptide (pg/ml)   1644 1709 — —
Troponin T (ng/liter) 0.00–0.02     — —
Alkaline phosphatase (U/liter) 39–117 195 152   252
Albumin (g/dl)   3.6 2.0   2.5
Lactic acid (mmol/liter)   1.2 —   0.6
Erythrocyte sedimentation rate (mm/hr)  0 30 — — —
C-reactive protein (mg/liter)  .0 — 117.0 — —
Lactate dehydrogenase (U/liter)   — 215 11 10 233
Uric acid (mg/dl) 3.4–7.2 — 6.4 3.6–8.5 11.5
Creatine kinase (U/liter) — — —   50
Iron (μg/dl) — — — 45–160 33
Total iron-binding capacity (μg/dl) — — — 23 4 138
Ferritin (μg/liter) — — — 2 00 978",Idiopathic multicentric Castleman's disease.,Idiopathic multicentric Castleman's disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 55-year-old man was transferred to this hospital for evaluation of a mediastinal mass that was identified as part of an evaluation for waxing and waning fevers, night sweats, and fatigue.
The patient had been well until 3 months before admission to this hospital, when fatigue and a transient pruritic maculopapular rash on the forearm developed. During the next 6 weeks, the forearm rash resolved but fatigue persisted. The patient began to take naps during the daytime and was unable to put in full days at his job in construction work. He also began to have night sweats and fevers with temperatures of up to 37.8[degrees]C.
Twenty-seven days before admission to this hospital, the patient found that he was unable to work because of fatigue, and he sought evaluation in the emergency department of another hospital. Blood tests for anaplasma and babesia nucleic acids were negative, but screening and confirmatory tests for Lyme disease IgM and IgG were positive. A diagnosis of Lyme disease was made, and treatment with doxycycline was initiated. Because gastrointestinal upset developed, doxycycline was discontinued and amoxicillin was prescribed for the remainder of the 14-day course.
Sixteen days before admission to this hospital, the patient began to have chest discomfort, which he described as a sensation of a ""softball"" in his left lower chest. The chest discomfort limited his ability to breathe, and his primary care physician referred him to the emergency department of the other hospital. On evaluation, he reported increasing fatigue and malaise, night sweats, and fevers, along with diffuse arthralgias and myalgias, headache, photophobia with some visual flashes, dyspnea on exertion, edema, a pruritic erythematous rash on his chest, anorexia, nausea, vomiting, abdominal discomfort and distention, and watery diarrhea that occurred three times per day.
On examination, the temperature was 36.8[degrees]C, the blood pressure 145/84 mm Hg, the heart rate 61 beats per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The weight was 83.9 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 28.1. There was a faint diffuse erythematous macular rash on the anterior portion of the chest. The abdomen was mildly distended and diffusely tender. Blood levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, and lipase were normal; other laboratory test results are shown in Table 1. Blood was obtained for microbiologic culture. An electrocardiogram was normal. Intravenous normal saline and oral acetaminophen were administered, as was empirical treatment with intravenous piperacillin-tazobactam, hydromorphone, and ondansetron. The patient was admitted to the other hospital.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Reece J. Goiffon: Fifteen days before admission to this hospital, computed tomography (CT) of the chest, abdomen, and pelvis (Figure 1A, 1B, and 1C), performed without the administration of intravenous contrast material, revealed a bilobed heterogeneous soft-tissue mass, measuring 6.1 cm by 2.8 cm, in the anterior mediastinum. There were multiple enlarged subcarinal and mediastinal lymph nodes (measuring up to 15 mm in short-axis diameter), multiple enlarged mesenteric lymph nodes (measuring up to 11 mm in short-axis diameter), mesenteric fat stranding, and trace ascites.	
Figure 1
Dr. Logeman: Abdominal discomfort persisted; piperacillin-tazobactam was discontinued and ceftriaxone was prescribed. Two days later, CT of the abdomen, performed without the administration of intravenous contrast material, revealed new pulmonary edema, new small bilateral pleural effusions, and an increased volume of ascites. The patient was transferred to a second hospital for further evaluation.
Physical examination was notable for mild abdominal tenderness and distention, as well as leg edema. Blood levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin and a urinalysis were normal; other laboratory test results are shown in Table 1. 18F-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) (Figure 1D) revealed indeterminate low-level FDG uptake in the anterior mediastinal soft tissue, as well as in pleural effusions and mediastinal lymph nodes.
During the next week, dyspnea and abdominal pain persisted. Edema increased, specifically in the abdomen, legs, and face; the weight increased to 93.0 kg. Intravenous ceftriaxone and metoclopramide and oral hydromorphone, ondansetron, and lactulose were administered. Additional laboratory tests were performed (Table 2).	
Table 2 
On the eighth day at the second hospital, video-assisted thoracic surgery was performed. The mediastinum reportedly appeared inflamed. The patient underwent an evacuation of pleural fluid and a biopsy of mediastinal soft tissue and lymph nodes primarily in the subcarinal window (level VII). On pathological examination of the biopsy specimens, the mediastinal soft tissue showed fibroconnective and adipose tissue with fibrosis, mild inflammation and fat necrosis, prominent capillary proliferation, and congestion; the lymph nodes were reportedly ""mildly abnormal."" Microbiologic evaluation of the biopsy specimens revealed occasional leukocytes but no acid-fast bacilli or fungal elements. On flow cytometry of the biopsy specimens, the mediastinal soft tissue did not show any abnormal cell populations; the lymph nodes contained polyclonal B-cell and heterogeneous T-cell populations, without immunophenotypic evidence of lymphoma. Bacterial, fungal, and mycobacterial cultures of the biopsy specimens were negative. Cytologic examination of the pleural fluid revealed reactive mesothelial cells, lymphocytes, and histiocytes but no malignant cells.
After the procedure, the creatinine level increased to 2.93 mg per deciliter (reference range, 0.50 to 1.30). Examination of urinary sediment revealed hyaline and granular casts. Intravenous furosemide was administered. On the 15th day at the second hospital, the patient was transferred to this hospital.
On arrival, the patient reported persistent fatigue, mild dyspnea, abdominal distention, edema, and anorexia. Nausea, vomiting, diarrhea, and the chest rash had resolved. Fevers and night sweats had occurred in a waxing and waning pattern during the previous weeks. He reported intermittent photophobia and headache, without neck stiffness or phonophobia, and had no other neurologic symptoms.
The patient had no history of illness and had not received routine medical care as an adult. He took ibuprofen and acetaminophen as needed and had no known allergies to medications. He had been exposed to dust through his job in construction work. He lived with his wife, child, and pet dog and cat in a coastal wooded community in New England. He frequently spent time outdoors, either working or playing golf, and had received multiple tick bites. He had traveled to the Mediterranean and Oceania regions in previous years and, more recently, to the southwestern United States. The patient had never used tobacco or illicit drugs and drank beer rarely. His father had had prostate cancer and colon cancer.
On examination, the temperature was 36.8[degrees]C, the blood pressure 148/82 mm Hg, the heart rate 78 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 93% while the patient was breathing ambient air. The weight was 91.7 kg. Neurologic examination was normal, and there was no nuchal rigidity. There were inspiratory crackles in the left lung. The abdomen was mildly distended and diffusely tender. Mild fluctuance was noted on the right side of the chest, at the site of the surgical incision. There was no palpable cervical, supraclavicular, submandibular, submental, axillary, or inguinal lymphadenopathy. There was 2+ pitting edema in the legs.
Blood levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, ceruloplasmin, fibrinogen, folate, globulin, haptoglobin, and vitamin B12 were normal; other laboratory test results are shown in Table 1. Urinalysis showed cloudy yellow urine with 2+ protein and 3 to 5 red cells per high-power field (reference range, 0 to 2). An electrocardiogram was normal.
Dr. Goiffon: CT of the chest, abdomen, and pelvis (Figure 1E), performed after the administration of intravenous contrast material, revealed an anterior mediastinal mass, measuring 6.1 cm by 1.9 cm, which was slightly smaller than it had been on the previous chest CT. There were enlarged perivascular, paratracheal, subcarinal, and aortopulmonary mediastinal lymph nodes (measuring up to 12 mm in short-axis diameter) with heterogeneous enhancement. Increased pulmonary edema, moderate bilateral pleural effusions, moderate-volume ascites, mild splenomegaly, and multiple subcentimeter mesenteric lymph nodes were detected.
Dr. Logeman: On the third hospital day, magnetic resonance imaging (MRI) of the head revealed no abnormalities. On the fourth day, a transthoracic echocardiogram was normal. Intravenous furosemide and oral acetaminophen were administered. Lumbar puncture was performed, and 26 ml of colorless fluid was removed; opening pressure was not measured. Results of cerebrospinal fluid analysis are shown in Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org. On the fifth day, renal ultrasonography revealed kidneys of normal size with normal parenchyma and no hydronephrosis. Diagnostic paracentesis was performed; results of ascitic fluid analysis are shown in Table S1.
Dr. Goiffon: On the 13th day, MRI of the chest was started but could not be completed because the patient had respiratory distress when placed in the prone position. Sequences that were obtained before termination of the study (Figure 1F) showed an anterior mediastinal soft-tissue mass with hypointensity on steady-state gradient echo imaging; the mass was smaller than it had been on chest CT performed before transfer to this hospital. In addition, there were enlarged mediastinal lymph nodes, large bilateral pleural effusions, ascites, and a hematoma at the site of the surgical incision.
Dr. Logeman: Additional laboratory tests were performed (Table 2). A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 55-year-old man was transferred to this hospital for evaluation of a mediastinal mass that was identified as part of an evaluation for waxing and waning fevers, night sweats, and fatigue.
The patient had been well until 3 months before admission to this hospital, when fatigue and a transient pruritic maculopapular rash on the forearm developed. During the next 6 weeks, the forearm rash resolved but fatigue persisted. The patient began to take naps during the daytime and was unable to put in full days at his job in construction work. He also began to have night sweats and fevers with temperatures of up to 37.8[degrees]C.
Twenty-seven days before admission to this hospital, the patient found that he was unable to work because of fatigue, and he sought evaluation in the emergency department of another hospital. Blood tests for anaplasma and babesia nucleic acids were negative, but screening and confirmatory tests for Lyme disease IgM and IgG were positive. A diagnosis of Lyme disease was made, and treatment with doxycycline was initiated. Because gastrointestinal upset developed, doxycycline was discontinued and amoxicillin was prescribed for the remainder of the 14-day course.
Sixteen days before admission to this hospital, the patient began to have chest discomfort, which he described as a sensation of a ""softball"" in his left lower chest. The chest discomfort limited his ability to breathe, and his primary care physician referred him to the emergency department of the other hospital. On evaluation, he reported increasing fatigue and malaise, night sweats, and fevers, along with diffuse arthralgias and myalgias, headache, photophobia with some visual flashes, dyspnea on exertion, edema, a pruritic erythematous rash on his chest, anorexia, nausea, vomiting, abdominal discomfort and distention, and watery diarrhea that occurred three times per day.
On examination, the temperature was 36.8[degrees]C, the blood pressure 145/84 mm Hg, the heart rate 61 beats per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The weight was 83.9 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 28.1. There was a faint diffuse erythematous macular rash on the anterior portion of the chest. The abdomen was mildly distended and diffusely tender. Blood levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, and lipase were normal; other laboratory test results are shown in Table 1. Blood was obtained for microbiologic culture. An electrocardiogram was normal. Intravenous normal saline and oral acetaminophen were administered, as was empirical treatment with intravenous piperacillin-tazobactam, hydromorphone, and ondansetron. The patient was admitted to the other hospital.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Reece J. Goiffon: Fifteen days before admission to this hospital, computed tomography (CT) of the chest, abdomen, and pelvis (Figure 1A, 1B, and 1C), performed without the administration of intravenous contrast material, revealed a bilobed heterogeneous soft-tissue mass, measuring 6.1 cm by 2.8 cm, in the anterior mediastinum. There were multiple enlarged subcarinal and mediastinal lymph nodes (measuring up to 15 mm in short-axis diameter), multiple enlarged mesenteric lymph nodes (measuring up to 11 mm in short-axis diameter), mesenteric fat stranding, and trace ascites.	
Figure 1
Dr. Logeman: Abdominal discomfort persisted; piperacillin-tazobactam was discontinued and ceftriaxone was prescribed. Two days later, CT of the abdomen, performed without the administration of intravenous contrast material, revealed new pulmonary edema, new small bilateral pleural effusions, and an increased volume of ascites. The patient was transferred to a second hospital for further evaluation.
Physical examination was notable for mild abdominal tenderness and distention, as well as leg edema. Blood levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin and a urinalysis were normal; other laboratory test results are shown in Table 1. 18F-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) (Figure 1D) revealed indeterminate low-level FDG uptake in the anterior mediastinal soft tissue, as well as in pleural effusions and mediastinal lymph nodes.
During the next week, dyspnea and abdominal pain persisted. Edema increased, specifically in the abdomen, legs, and face; the weight increased to 93.0 kg. Intravenous ceftriaxone and metoclopramide and oral hydromorphone, ondansetron, and lactulose were administered. Additional laboratory tests were performed (Table 2).	
Table 2 
On the eighth day at the second hospital, video-assisted thoracic surgery was performed. The mediastinum reportedly appeared inflamed. The patient underwent an evacuation of pleural fluid and a biopsy of mediastinal soft tissue and lymph nodes primarily in the subcarinal window (level VII). On pathological examination of the biopsy specimens, the mediastinal soft tissue showed fibroconnective and adipose tissue with fibrosis, mild inflammation and fat necrosis, prominent capillary proliferation, and congestion; the lymph nodes were reportedly ""mildly abnormal."" Microbiologic evaluation of the biopsy specimens revealed occasional leukocytes but no acid-fast bacilli or fungal elements. On flow cytometry of the biopsy specimens, the mediastinal soft tissue did not show any abnormal cell populations; the lymph nodes contained polyclonal B-cell and heterogeneous T-cell populations, without immunophenotypic evidence of lymphoma. Bacterial, fungal, and mycobacterial cultures of the biopsy specimens were negative. Cytologic examination of the pleural fluid revealed reactive mesothelial cells, lymphocytes, and histiocytes but no malignant cells.
After the procedure, the creatinine level increased to 2.93 mg per deciliter (reference range, 0.50 to 1.30). Examination of urinary sediment revealed hyaline and granular casts. Intravenous furosemide was administered. On the 15th day at the second hospital, the patient was transferred to this hospital.
On arrival, the patient reported persistent fatigue, mild dyspnea, abdominal distention, edema, and anorexia. Nausea, vomiting, diarrhea, and the chest rash had resolved. Fevers and night sweats had occurred in a waxing and waning pattern during the previous weeks. He reported intermittent photophobia and headache, without neck stiffness or phonophobia, and had no other neurologic symptoms.
The patient had no history of illness and had not received routine medical care as an adult. He took ibuprofen and acetaminophen as needed and had no known allergies to medications. He had been exposed to dust through his job in construction work. He lived with his wife, child, and pet dog and cat in a coastal wooded community in New England. He frequently spent time outdoors, either working or playing golf, and had received multiple tick bites. He had traveled to the Mediterranean and Oceania regions in previous years and, more recently, to the southwestern United States. The patient had never used tobacco or illicit drugs and drank beer rarely. His father had had prostate cancer and colon cancer.
On examination, the temperature was 36.8[degrees]C, the blood pressure 148/82 mm Hg, the heart rate 78 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 93% while the patient was breathing ambient air. The weight was 91.7 kg. Neurologic examination was normal, and there was no nuchal rigidity. There were inspiratory crackles in the left lung. The abdomen was mildly distended and diffusely tender. Mild fluctuance was noted on the right side of the chest, at the site of the surgical incision. There was no palpable cervical, supraclavicular, submandibular, submental, axillary, or inguinal lymphadenopathy. There was 2+ pitting edema in the legs.
Blood levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, ceruloplasmin, fibrinogen, folate, globulin, haptoglobin, and vitamin B12 were normal; other laboratory test results are shown in Table 1. Urinalysis showed cloudy yellow urine with 2+ protein and 3 to 5 red cells per high-power field (reference range, 0 to 2). An electrocardiogram was normal.
Dr. Goiffon: CT of the chest, abdomen, and pelvis (Figure 1E), performed after the administration of intravenous contrast material, revealed an anterior mediastinal mass, measuring 6.1 cm by 1.9 cm, which was slightly smaller than it had been on the previous chest CT. There were enlarged perivascular, paratracheal, subcarinal, and aortopulmonary mediastinal lymph nodes (measuring up to 12 mm in short-axis diameter) with heterogeneous enhancement. Increased pulmonary edema, moderate bilateral pleural effusions, moderate-volume ascites, mild splenomegaly, and multiple subcentimeter mesenteric lymph nodes were detected.
Dr. Logeman: On the third hospital day, magnetic resonance imaging (MRI) of the head revealed no abnormalities. On the fourth day, a transthoracic echocardiogram was normal. Intravenous furosemide and oral acetaminophen were administered. Lumbar puncture was performed, and 26 ml of colorless fluid was removed; opening pressure was not measured. Results of cerebrospinal fluid analysis are shown in Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org. On the fifth day, renal ultrasonography revealed kidneys of normal size with normal parenchyma and no hydronephrosis. Diagnostic paracentesis was performed; results of ascitic fluid analysis are shown in Table S1.
Dr. Goiffon: On the 13th day, MRI of the chest was started but could not be completed because the patient had respiratory distress when placed in the prone position. Sequences that were obtained before termination of the study (Figure 1F) showed an anterior mediastinal soft-tissue mass with hypointensity on steady-state gradient echo imaging; the mass was smaller than it had been on chest CT performed before transfer to this hospital. In addition, there were enlarged mediastinal lymph nodes, large bilateral pleural effusions, ascites, and a hematoma at the site of the surgical incision.
Dr. Logeman: Additional laboratory tests were performed (Table 2). A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fatigue, night sweats, fevers, and a mediastinal mass are indicative of a systemic disease. The presence of a mediastinal mass suggests a malignancy such as lymphoma or thymoma, or an infectious disease such as tuberculosis. However, the biopsy of the mediastinal mass and lymph nodes did not show any malignant cells or infectious organisms. The patient's symptoms did not improve with antibiotic treatment, which makes an infectious cause less likely. The patient's history of multiple tick bites and positive tests for Lyme disease suggest that this could be the cause of his symptoms. However, his symptoms did not improve with treatment for Lyme disease. The patient's symptoms and the presence of a mediastinal mass that is not explained by malignancy or infection suggest a systemic inflammatory or autoimmune disease. The patient's elevated sedimentation rate and C-reactive protein level support this. The patient's history of exposure to dust through his job in construction work raises the possibility of a disease related to dust exposure, such as sarcoidosis. Sarcoidosis is a systemic inflammatory disease that can cause non-caseating granulomas in various organs, including the lymph nodes and lungs. It can cause fatigue, night sweats, and fevers, as well as a mediastinal mass due to lymph node involvement. The patient's symptoms, the presence of a mediastinal mass, and the lack of evidence for other causes suggest that sarcoidosis is the most likely diagnosis.\n\nDiagnosis: Sarcoidosis""
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        ""content"": ""The patient's symptoms of fatigue, night sweats, fevers, and a mediastinal mass are suggestive of a malignancy such as lymphoma. However, the biopsy of the mediastinal mass and lymph nodes did not show any evidence of malignancy. The patient also had a positive test for Lyme disease and was treated with antibiotics, but his symptoms did not improve, suggesting that Lyme disease is not the cause of his current symptoms. The patient's symptoms and the presence of a mediastinal mass could also be due to an infection, but cultures from the biopsy were negative. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the waxing and waning nature of his symptoms, are suggestive of an inflammatory or autoimmune condition. The patient's symptoms and the presence of a mediastinal mass, along with the wax""
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        ""content"": ""The patient is a 55-year-old man with a history of construction work, outdoor activities, and multiple tick bites. He presents with a mediastinal mass, fevers, night sweats, fatigue, and a rash. His symptoms and history suggest an infectious or neoplastic process. The differential diagnosis includes lymphoma, sarcoidosis, tuberculosis, and Lyme disease. The patient's positive Lyme disease IgM and IgG tests initially suggested Lyme disease, but his symptoms did not improve with appropriate antibiotic treatment, making this diagnosis less likely. The patient's mediastinal mass and lymphadenopathy could suggest lymphoma, but biopsy of the mediastinal mass and lymph nodes did not show any abnormal cell populations or evidence of lymphoma. Sarcoidosis could also present with a mediastinal mass and lymphadenopathy, but the patient's biopsy did not show non-caseating granulomas, which are characteristic of sarcoidosis. Tuberculosis could also present with a mediastinal mass and lymphadenopathy, but the patient's biopsy did not show acid-fast bacilli and cultures were negative for mycobacteria. The patient's history of multiple tick bites, outdoor activities, and initial positive Lyme disease tests suggest a tick-borne illness. The patient's symptoms of fevers, night sweats, and fatigue, along with his mediastinal mass and lymphadenopathy, could be consistent with a disseminated tick-borne illness such as babesiosis or anaplasmosis, but his blood tests for anaplasma and babesia nucleic acids were negative. Given the patient's history and presentation, the most likely diagnosis is a tick-borne illness that was not initially tested for.\n\nDiagnosis: Unspecified tick-borne illness.""
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}",Unspecified tick-borne illness,N
10.1056/NEJMcpc2201234,Case 15-2022: A 57-Year-Old Man with Persistent Cough and Pulmonary Opacities,"Hemoglobin (g/dl)   15.4 14.7 12.4 13.6
Hematocrit (%)   44.5 46.2 40.9 42.8
White-cell count (per μl)   20,300 15,480 18,120 21,180
Differential count (%)
Neutrophils   80.9 77.5 90.6 83.9
Lymphocytes   12.3 17.1 5.8 11.6
Monocytes   4.8 4.1 3.1 3.7
Eosinophils   0.4 0.8 0 0.3
Platelet count (per μl) 150,000–
400,000
255,000 199,000 480,000 406,000
Lactate (mmol/liter)†   2.8 — 2.6 1.8
Erythrocyte sedimentation rate 
(mm/hr)
  16 — 54 —
C-reactive protein (mg/liter)   126.6 — 149.7 —
1,3-β-d-glucan (pg/ml) <60 488 — 420 >500
Venous blood gases
Fraction of inspired oxygen — — — — 0.4
pH   — — — 7.36
Partial pressure of carbon 
dioxide (mm Hg)
  — — — 64
Partial pressure of oxygen 
(mm Hg)
  — — — 26",Aspiration pneumonia,Diffuse aspiration bronchiolitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 57-year-old man was evaluated at this hospital because of persistent cough and pulmonary opacities.
Six years before the current admission, the patient received a diagnosis of polyarteritis nodosa after fevers, arthralgias, abdominal pain, and testicular pain had developed. He was treated with six cycles of cyclophosphamide, followed by maintenance therapy with prednisone and weekly methotrexate. He was treated intermittently with escalating doses of prednisone because of episodic worsening of the arthralgias; the most recent such treatment was given 5 months before the current admission. At that time, owing to an exacerbation of pain associated with the arthralgias and at the direction of his physician, he increased the amount of oxycodone he had been taking. He also reported fever and weight loss. Imaging studies were obtained.
Dr. Jeanna M. Harvey Barnes: Five months before the current admission, computed tomography (CT) of the chest, abdomen, and pelvis was performed after the administration of intravenous contrast material. Chest CT (Figure 1A and 1B) revealed mild centrilobular emphysema and small pulmonary nodules that appeared unchanged from those seen on imaging that had been performed 6 years earlier. There was also diffuse thickening of the bronchial wall, layering secretions in the trachea and right main-stem bronchus, a mildly patulous esophagus, and a small hiatal hernia. There were no clinically significant findings on imaging of the abdomen or pelvis.	
Figure 1
Dr. Alba: A test for Mycobacterium tuberculosis was negative. Serum protein electrophoresis results were normal, as was the IgG level.
Three months before the current admission, the patient had fevers and a cough productive of green sputum. The temperature was 37.3[degrees]C and the oxygen saturation 89% while he was breathing ambient air. Thrush was present in the oropharynx. Auscultation of the chest revealed crackles and wheezing in the right lung. Blood levels of electrolytes, lipase, amylase, lactate dehydrogenase, and troponin T were normal, as were the results of liver-function and kidney-function tests; other laboratory test results are shown in Table 1.	
Table 1 
Dr. Harvey Barnes: A chest radiograph (Figure 1C) showed patchy and confluent opacities predominantly in the right mid and lower lung.
Dr. Alba: The patient was admitted to this hospital, and empirical treatment with intravenous vancomycin, cefepime, and levofloxacin was administered. A blood test for cryptococcal antigen and a urine test for legionella antigen were negative. A sputum culture grew normal respiratory flora and Candida albicans; a test for Pneumocystis jirovecii was negative. During the next several days, fever resolved and the oxygen saturation and white-cell count normalized. On the fifth hospital day, the patient was discharged home to complete a 14-day course of levofloxacin. After he completed the course of levofloxacin, his cough and constitutional symptoms abated partially but did not return to baseline. His primary care physician prescribed inhaled fluticasone-salmeterol and as-needed inhaled albuterol.
Six weeks after the patient was discharged from this hospital (approximately 5 weeks before the current admission), his wife began to have a nonproductive cough and rhinorrhea; several days later, the patient had similar symptoms, along with increased production of brown sputum. He sought medical attention after awakening with coughing and dyspnea. The temperature was 38.4[degrees]C and the oxygen saturation 89% while he was breathing ambient air.
Dr. Harvey Barnes: A chest radiograph (Figure 1D) obtained 1 month before the current admission showed patchy opacities in the right upper, middle, and lower lobes.
Dr. Alba: Electrolyte levels were normal, as were the results of liver-function and kidney-function tests; other laboratory test results are shown in Table 1. The patient was again admitted to this hospital, and empirical treatment with intravenous vancomycin, cefepime, and azithromycin; oral prednisone; and inhaled albuterol and ipratropium was administered. A sputum culture grew normal respiratory flora and C. albicans. After two days, the patient was discharged home to complete a 7-day course of levofloxacin.
Over the course of the next 3 weeks, the patient had malaise, productive cough, fever, and sweats. He stopped smoking cigarettes.
Eight days before the current admission, the patient was referred to the emergency department of this hospital for evaluation. On examination, the temperature was 37.2[degrees]C and the oxygen saturation 94% while he was breathing ambient air. There were crackles in both lung bases and in the right middle lung field, with no wheezes. Blood levels of electrolytes and lactate dehydrogenase were normal, as were the results of liver-function and kidney-function tests and urinalysis; other laboratory test results are shown in Table 1.
Dr. Harvey Barnes: A chest radiograph (Figure 2A) showed multifocal reticulonodular and patchy opacities, which were confluent in the right lower lobe. CT of the chest (Figure 2B and 2C), performed without the administration of intravenous contrast material, revealed multifocal clustered, centrilobular nodules and opacities in a tree-in-bud pattern with scattered areas of focal consolidation that were present predominantly in the right middle and lower lobes. There was associated mild mediastinal and right hilar lymphadenopathy that had not been present on the previous chest CT examination.	
Figure 2
Dr. Alba: The patient was again admitted to this hospital, and additional testing was performed. Tests for antineutrophil cytoplasmic antibodies and anti-double-stranded DNA antibodies were negative, and blood levels of C3 and C4 were normal. A urine test for legionella antigen was negative.
On the third hospital day, a bronchoscopy and a transbronchial biopsy were performed. The bronchoalveolar-lavage (BAL) fluid obtained from the right middle lobe was cloudy; analysis of the fluid revealed 888 nucleated cells per microliter (of which 48% were neutrophils and 2% were lymphocytes, with no eosinophils). Gram's staining of the BAL fluid revealed neutrophils and sparse growth of gram-positive cocci. Staining for acid-fast organisms was negative; culture grew normal respiratory flora and C. albicans. Tests of the BAL fluid for influenza virus, adenovirus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus, P. jirovecii, histoplasma antigen, and blastomyces antigen were negative, as were cultures for cytomegalovirus and herpes simplex virus. An interferon-[gamma] release assay for M. tuberculosis was also negative. The patient was discharged home on the third hospital day, with follow-up scheduled in the pulmonary clinic for 3 weeks later.
Four days after the patient was discharged, a BAL test for galactomannan returned a positive result (antigen index, >=3.750; negative test, <0.5), and the patient was readmitted to this hospital. He reported ongoing dyspnea, cough with thick white sputum, and persistent fever with a temperature of up to 39.3[degrees]C. A review of systems was notable for diffuse chronic arthralgias, a bitter taste in the mouth, and intermittent dysphagia. There was no chest pain, edema, orthopnea, nausea, vomiting, jaundice, or rash, and he had no known current sick contacts. The weight was 5 kg lower than that recorded 1 year earlier.
Medical history was notable for polyarteritis nodosa, deep venous thrombosis, gastroesophageal reflux disease (GERD), pancreatitis in the context of choledocholithiasis, hypertension, dyslipidemia, diabetes mellitus, osteopenia, and chronic neuropathic pain. Medications included aspirin, prednisone, methotrexate, trimethoprim-sulfamethoxazole, folate supplementation, metformin, atenolol, simvastatin, pregabalin, and as-needed oxycodone, as well as inhaled fluticasone-salmeterol and albuterol as needed. Lisinopril had reportedly caused pancreatic inflammation; there were no other known adverse reactions to medications. The patient was of White European ancestry. He lived in New England with his wife and was retired from an office position. Three decades earlier, he had worked in a machine shop where solvents, fuels, and sulfur compounds were used but had had no known exposure to these agents. There was no history of exposure to mold, pets, or asbestos. He had received influenza and pneumococcal vaccines. He and his wife had traveled within the United States and to the Caribbean. He had smoked 1.5 packs of cigarettes per day for 30 years but had quit in the weeks before the current admission. He had previously smoked marijuana, rarely consumed alcohol, and never used other substances. There was no family history of autoimmune or pulmonary disease; his father had died from colorectal cancer, and his mother had had esophageal cancer and had died after a stroke. His three adult children were healthy.
The temperature was 36.6[degrees]C, the heart rate 75 beats per minute, the blood pressure 135/69 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 91% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 6 liters per minute. He had a slightly cushingoid appearance and was tachypneic, although he was able to speak in full sentences. Auscultation of the chest revealed rales at the right lung base, rhonchi during both the inspiratory and expiratory phases that were more pronounced in the right lung than in the left lung, and intermittent inspiratory wheezing in the right lung. The rest of the examination was normal.
Dr. Harvey Barnes: A chest radiograph (Figure 2D) showed progression of the diffuse bilateral reticulonodular opacities, with additional patchy opacities in the right lung and left lower lobe, as compared with the image obtained 1 week earlier.
Dr. Alba: Blood levels of electrolytes, amylase, lipase, N-terminal pro-B-type natriuretic peptide, and troponin T were normal, as were the results of tests of kidney and liver function; other laboratory test results are shown in Table 1. Urinalysis was normal, and a urine test for legionella antigen was negative.
The BAL-fluid culture obtained during the previous admission grew enterococcus species, C. albicans, and C. glabrata; no mycobacteria grew in any of three induced sputum samples obtained during the previous admission. Empirical treatment with intravenous voriconazole was initiated, and ongoing treatment with methotrexate was interrupted.
Cytologic analysis of the BAL fluid and the transbronchial-biopsy specimen obtained during the previous admission revealed evidence of acute inflammation, bronchial columnar cells, and pulmonary macrophages. There were no malignant cells. Evaluation of the bronchial mucosa revealed no abnormalities.
On the second hospital day, the temperature was 37.9[degrees]C and the oxygen saturation 91% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 5 liters per minute.
Dr. Harvey Barnes: Repeat CT of the chest (Figure 2E and 2F) was performed after the administration of intravenous contrast material as part of a pulmonary embolism protocol. This imaging study revealed extensive centrilobular pulmonary nodules, opacities in a tree-in-bud pattern, and patchy ground-glass opacities. There was bronchial wall thickening with mucus plugging, predominantly affecting the lower lobes. There were additional areas of nodular consolidation that were more prominent in the right lung than in the left lung. These findings indicated a progression of disease as compared with the chest CT performed 1 week before the current admission. There was no evidence of pulmonary embolism.
Dr. Alba: Additional induced sputum samples were obtained for culture; Gram's staining revealed abundant neutrophils and abundant mixed gram-positive and gram-negative organisms.
On the third hospital day, the temperature was 36.9[degrees]C and the oxygen saturation 96% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 3 liters per minute.
Diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 57-year-old man was evaluated at this hospital because of persistent cough and pulmonary opacities.
Six years before the current admission, the patient received a diagnosis of polyarteritis nodosa after fevers, arthralgias, abdominal pain, and testicular pain had developed. He was treated with six cycles of cyclophosphamide, followed by maintenance therapy with prednisone and weekly methotrexate. He was treated intermittently with escalating doses of prednisone because of episodic worsening of the arthralgias; the most recent such treatment was given 5 months before the current admission. At that time, owing to an exacerbation of pain associated with the arthralgias and at the direction of his physician, he increased the amount of oxycodone he had been taking. He also reported fever and weight loss. Imaging studies were obtained.
Dr. Jeanna M. Harvey Barnes: Five months before the current admission, computed tomography (CT) of the chest, abdomen, and pelvis was performed after the administration of intravenous contrast material. Chest CT (Figure 1A and 1B) revealed mild centrilobular emphysema and small pulmonary nodules that appeared unchanged from those seen on imaging that had been performed 6 years earlier. There was also diffuse thickening of the bronchial wall, layering secretions in the trachea and right main-stem bronchus, a mildly patulous esophagus, and a small hiatal hernia. There were no clinically significant findings on imaging of the abdomen or pelvis.	
Figure 1
Dr. Alba: A test for Mycobacterium tuberculosis was negative. Serum protein electrophoresis results were normal, as was the IgG level.
Three months before the current admission, the patient had fevers and a cough productive of green sputum. The temperature was 37.3[degrees]C and the oxygen saturation 89% while he was breathing ambient air. Thrush was present in the oropharynx. Auscultation of the chest revealed crackles and wheezing in the right lung. Blood levels of electrolytes, lipase, amylase, lactate dehydrogenase, and troponin T were normal, as were the results of liver-function and kidney-function tests; other laboratory test results are shown in Table 1.	
Table 1 
Dr. Harvey Barnes: A chest radiograph (Figure 1C) showed patchy and confluent opacities predominantly in the right mid and lower lung.
Dr. Alba: The patient was admitted to this hospital, and empirical treatment with intravenous vancomycin, cefepime, and levofloxacin was administered. A blood test for cryptococcal antigen and a urine test for legionella antigen were negative. A sputum culture grew normal respiratory flora and Candida albicans; a test for Pneumocystis jirovecii was negative. During the next several days, fever resolved and the oxygen saturation and white-cell count normalized. On the fifth hospital day, the patient was discharged home to complete a 14-day course of levofloxacin. After he completed the course of levofloxacin, his cough and constitutional symptoms abated partially but did not return to baseline. His primary care physician prescribed inhaled fluticasone-salmeterol and as-needed inhaled albuterol.
Six weeks after the patient was discharged from this hospital (approximately 5 weeks before the current admission), his wife began to have a nonproductive cough and rhinorrhea; several days later, the patient had similar symptoms, along with increased production of brown sputum. He sought medical attention after awakening with coughing and dyspnea. The temperature was 38.4[degrees]C and the oxygen saturation 89% while he was breathing ambient air.
Dr. Harvey Barnes: A chest radiograph (Figure 1D) obtained 1 month before the current admission showed patchy opacities in the right upper, middle, and lower lobes.
Dr. Alba: Electrolyte levels were normal, as were the results of liver-function and kidney-function tests; other laboratory test results are shown in Table 1. The patient was again admitted to this hospital, and empirical treatment with intravenous vancomycin, cefepime, and azithromycin; oral prednisone; and inhaled albuterol and ipratropium was administered. A sputum culture grew normal respiratory flora and C. albicans. After two days, the patient was discharged home to complete a 7-day course of levofloxacin.
Over the course of the next 3 weeks, the patient had malaise, productive cough, fever, and sweats. He stopped smoking cigarettes.
Eight days before the current admission, the patient was referred to the emergency department of this hospital for evaluation. On examination, the temperature was 37.2[degrees]C and the oxygen saturation 94% while he was breathing ambient air. There were crackles in both lung bases and in the right middle lung field, with no wheezes. Blood levels of electrolytes and lactate dehydrogenase were normal, as were the results of liver-function and kidney-function tests and urinalysis; other laboratory test results are shown in Table 1.
Dr. Harvey Barnes: A chest radiograph (Figure 2A) showed multifocal reticulonodular and patchy opacities, which were confluent in the right lower lobe. CT of the chest (Figure 2B and 2C), performed without the administration of intravenous contrast material, revealed multifocal clustered, centrilobular nodules and opacities in a tree-in-bud pattern with scattered areas of focal consolidation that were present predominantly in the right middle and lower lobes. There was associated mild mediastinal and right hilar lymphadenopathy that had not been present on the previous chest CT examination.	
Figure 2
Dr. Alba: The patient was again admitted to this hospital, and additional testing was performed. Tests for antineutrophil cytoplasmic antibodies and anti-double-stranded DNA antibodies were negative, and blood levels of C3 and C4 were normal. A urine test for legionella antigen was negative.
On the third hospital day, a bronchoscopy and a transbronchial biopsy were performed. The bronchoalveolar-lavage (BAL) fluid obtained from the right middle lobe was cloudy; analysis of the fluid revealed 888 nucleated cells per microliter (of which 48% were neutrophils and 2% were lymphocytes, with no eosinophils). Gram's staining of the BAL fluid revealed neutrophils and sparse growth of gram-positive cocci. Staining for acid-fast organisms was negative; culture grew normal respiratory flora and C. albicans. Tests of the BAL fluid for influenza virus, adenovirus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus, P. jirovecii, histoplasma antigen, and blastomyces antigen were negative, as were cultures for cytomegalovirus and herpes simplex virus. An interferon-[gamma] release assay for M. tuberculosis was also negative. The patient was discharged home on the third hospital day, with follow-up scheduled in the pulmonary clinic for 3 weeks later.
Four days after the patient was discharged, a BAL test for galactomannan returned a positive result (antigen index, >=3.750; negative test, <0.5), and the patient was readmitted to this hospital. He reported ongoing dyspnea, cough with thick white sputum, and persistent fever with a temperature of up to 39.3[degrees]C. A review of systems was notable for diffuse chronic arthralgias, a bitter taste in the mouth, and intermittent dysphagia. There was no chest pain, edema, orthopnea, nausea, vomiting, jaundice, or rash, and he had no known current sick contacts. The weight was 5 kg lower than that recorded 1 year earlier.
Medical history was notable for polyarteritis nodosa, deep venous thrombosis, gastroesophageal reflux disease (GERD), pancreatitis in the context of choledocholithiasis, hypertension, dyslipidemia, diabetes mellitus, osteopenia, and chronic neuropathic pain. Medications included aspirin, prednisone, methotrexate, trimethoprim-sulfamethoxazole, folate supplementation, metformin, atenolol, simvastatin, pregabalin, and as-needed oxycodone, as well as inhaled fluticasone-salmeterol and albuterol as needed. Lisinopril had reportedly caused pancreatic inflammation; there were no other known adverse reactions to medications. The patient was of White European ancestry. He lived in New England with his wife and was retired from an office position. Three decades earlier, he had worked in a machine shop where solvents, fuels, and sulfur compounds were used but had had no known exposure to these agents. There was no history of exposure to mold, pets, or asbestos. He had received influenza and pneumococcal vaccines. He and his wife had traveled within the United States and to the Caribbean. He had smoked 1.5 packs of cigarettes per day for 30 years but had quit in the weeks before the current admission. He had previously smoked marijuana, rarely consumed alcohol, and never used other substances. There was no family history of autoimmune or pulmonary disease; his father had died from colorectal cancer, and his mother had had esophageal cancer and had died after a stroke. His three adult children were healthy.
The temperature was 36.6[degrees]C, the heart rate 75 beats per minute, the blood pressure 135/69 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 91% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 6 liters per minute. He had a slightly cushingoid appearance and was tachypneic, although he was able to speak in full sentences. Auscultation of the chest revealed rales at the right lung base, rhonchi during both the inspiratory and expiratory phases that were more pronounced in the right lung than in the left lung, and intermittent inspiratory wheezing in the right lung. The rest of the examination was normal.
Dr. Harvey Barnes: A chest radiograph (Figure 2D) showed progression of the diffuse bilateral reticulonodular opacities, with additional patchy opacities in the right lung and left lower lobe, as compared with the image obtained 1 week earlier.
Dr. Alba: Blood levels of electrolytes, amylase, lipase, N-terminal pro-B-type natriuretic peptide, and troponin T were normal, as were the results of tests of kidney and liver function; other laboratory test results are shown in Table 1. Urinalysis was normal, and a urine test for legionella antigen was negative.
The BAL-fluid culture obtained during the previous admission grew enterococcus species, C. albicans, and C. glabrata; no mycobacteria grew in any of three induced sputum samples obtained during the previous admission. Empirical treatment with intravenous voriconazole was initiated, and ongoing treatment with methotrexate was interrupted.
Cytologic analysis of the BAL fluid and the transbronchial-biopsy specimen obtained during the previous admission revealed evidence of acute inflammation, bronchial columnar cells, and pulmonary macrophages. There were no malignant cells. Evaluation of the bronchial mucosa revealed no abnormalities.
On the second hospital day, the temperature was 37.9[degrees]C and the oxygen saturation 91% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 5 liters per minute.
Dr. Harvey Barnes: Repeat CT of the chest (Figure 2E and 2F) was performed after the administration of intravenous contrast material as part of a pulmonary embolism protocol. This imaging study revealed extensive centrilobular pulmonary nodules, opacities in a tree-in-bud pattern, and patchy ground-glass opacities. There was bronchial wall thickening with mucus plugging, predominantly affecting the lower lobes. There were additional areas of nodular consolidation that were more prominent in the right lung than in the left lung. These findings indicated a progression of disease as compared with the chest CT performed 1 week before the current admission. There was no evidence of pulmonary embolism.
Dr. Alba: Additional induced sputum samples were obtained for culture; Gram's staining revealed abundant neutrophils and abundant mixed gram-positive and gram-negative organisms.
On the third hospital day, the temperature was 36.9[degrees]C and the oxygen saturation 96% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 3 liters per minute.
Diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of polyarteritis nodosa, a systemic vasculitis, and has been on immunosuppressive therapy for several years. He presents with persistent cough, fever, and pulmonary opacities on imaging. His sputum culture grew Candida albicans multiple times, but this is a common commensal organism and not typically pathogenic in the lungs. His bronchoalveolar lavage fluid was cloudy and showed neutrophils and gram-positive cocci, suggesting a bacterial infection. However, the most significant finding is the positive galactomannan test from the bronchoalveolar lavage fluid. Galactomannan is a component of the cell wall of Aspergillus species, and a positive test is indicative of invasive aspergillosis. This is a fungal infection that typically occurs in immunocompromised patients, such as this patient with a history of polyarteritis nodosa on immunosuppressive therapy. The CT findings of centrilobular nodules, tree-in-bud opacities, and patchy ground-glass opacities are also consistent with invasive pulmonary aspergillosis.\n\nDiagnosis: Invasive Pulmonary Aspergillosis.""
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        ""content"": ""The patient is a 57-year-old man with a history of polyarteritis nodosa who presents with persistent cough and pulmonary opacities. He has been treated with immunosuppressive therapy for his polyarteritis nodosa, which puts him at risk for opportunistic infections. His symptoms include fever, weight loss, and productive cough, which are suggestive of an infectious process. The differential diagnosis includes bacterial pneumonia, fungal infection, tuberculosis, and malignancy. His sputum cultures have grown normal respiratory flora and Candida albicans, but these organisms are not typically pathogenic in the lungs and are likely contaminants or colonizers. His chest CT shows centrilobular nodules, tree-in-bud opacities, and patchy ground-glass opacities, which are suggestive of an infectious process. His bronchoalveolar lavage fluid was positive for galactomannan, which is a component of the cell wall of Aspergillus, a type of fungus. This finding, along with his clinical presentation and radiographic findings, is highly suggestive of invasive pulmonary aspergillosis, a serious fungal infection that can occur in immunocompromised patients.\n\nDiagnosis: Invasive Pulmonary Aspergillosis.""
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10.1056/NEJMcpc2115856,Case 14-2022: A 57-Year-Old Man with Chylous Ascites.,"Red-cell count (per μl)  ,000 >3000
Nucleated-cell count (per μl) 269 226
Differential count (%)
Neutrophils 11 9
Mononuclear cells 89 24
Lymphocytes 0 58
Amylase (U/liter) 10 —
Cholesterol (mg/dl) 43 —
Triglycerides (mg/dl) 797 146
Total protein (g/dl) 1.3 1.4
Albumin (g/dl) 0.5 0.3
Glucose (mg/dl) 379 437
Lactate dehydrogenase (U/liter) 60 —","High-grade B-cell lymphoma, not otherwise specified.",B-cell lymphoma.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 57-year-old man was evaluated in the gastroenterology clinic of this hospital because of new ascites.
Twenty years before the current presentation, the patient began to have swelling of the legs, which initially occurred only after airplane trips. During the fifth decade of life, the leg swelling was present on a daily basis. Thirteen years before the current presentation, the patient began to have frequent bowel movements (up to four per day) with loose malodorous stools and increased flatus. He was evaluated in the gastroenterology clinic of this hospital. On examination, the abdomen was soft and nontender, with no evidence of organomegaly. There was pitting edema in both legs. The blood level of total protein was 5.5 g per deciliter (reference range, 6.0 to 8.3), and the blood albumin level was 3.1 g per deciliter (reference range, 3.3 to 5.0). Results of other liver-function tests, including liver enzyme levels, were normal. The protein level in a 24-hour urine sample was normal. The blood alpha1-antitrypsin level was 173 mg per deciliter (reference value, <54). Blood levels of IgG, IgA, and IgM were low. Serologic tests for anti-tissue transglutaminase antibodies and anti-giardia antibodies were negative.
Dr. Mark A. Anderson: Computed tomographic (CT) enterography of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed diffuse mural thickening and hyperenhancement of the small bowel, with no evidence of stricturing or obstruction (Figure 1A and 1B). In addition, there was trace ascites (Figure 1B).	
Figure 1 
Dr. Uchida: Esophagogastroduodenoscopy (EGD) and colonoscopy revealed no visible abnormalities. A random biopsy specimen of the duodenum showed a focal area with more than 70 eosinophils per high-power field; a biopsy specimen of the gastric antrum showed scattered eosinophils in the lamina propria. A working diagnosis of protein-losing enteropathy was made, although neither a 2-week course of oral prednisone nor a 6-week course of oral budesonide led to a decrease in the number of bowel movements or leg edema. No further treatment was pursued.
Eleven years before the current presentation, the patient was evaluated in the gastroenterology clinic of this hospital. There had been no weight loss or recurrent infections, but leg edema persisted. Repeat EGD revealed no visible abnormalities, and a random biopsy specimen of the duodenum showed fewer eosinophils than the previous specimen, with no epithelial damage. CT enterography revealed diffuse wall thickening of the entire small bowel and trace ascites. Treatment for protein-losing enteropathy - which included limiting salt intake, increasing dietary protein, and wearing compression stockings - was recommended. During the next 10 years, the leg edema was stable and was occasionally treated with diuretic agents, which did not lead to substantial improvement.
Six months before the current presentation, the patient began to have dyspnea on exertion. Three months before this presentation, abdominal distention developed. The patient initially attributed the dyspnea and abdominal distention to weight gain due to reduced physical activity during quarantine for the coronavirus disease 2019 (Covid-19) pandemic. Six weeks before this presentation, the patient was evaluated by his primary care physician in a video conference. On the basis of this evaluation, laboratory and imaging studies were obtained. The blood level of total protein was 4.5 g per deciliter (updated reference range, 6.4 to 8.3), and the blood albumin level was 2.1 g per deciliter. The complete blood count, blood levels of electrolytes and glucose, and results of liver-function and kidney-function tests were normal.
Dr. Anderson: CT of the chest, performed after the administration of intravenous contrast material, revealed multiple small pulmonary nodules, enlarged subcarinal and upper mesenteric lymph nodes, and moderate-volume ascites in the upper abdomen.
Dr. Uchida: Three weeks later, paracentesis was performed, and 3.1 liters of milky-appearing ascitic fluid were removed. Results of the ascitic fluid analysis are shown in Table 1. Cytologic examination of the ascitic fluid revealed no malignant cells. The patient was referred to the gastroenterology clinic of this hospital for further evaluation.	
Table 1 
On the current presentation, the patient reported that he was having bowel movements with normally formed stools and no abdominal pain. His wife had noticed that he appeared to be moving slowly when performing activities of daily living and that he had lost muscle mass in his arms. There was no history of abdominal surgery or trauma to the abdomen. Other medical history included type 2 diabetes mellitus, psoriasis, osteoarthritis, and hypogammaglobulinemia. There was no history of recurrent infections, asthma, or atopic dermatitis. Medications included aspirin, insulin glargine, and metformin. There were no known drug allergies. The patient lived with his wife in a suburb of Boston and worked in an office. He was a lifelong nonsmoker, drank alcohol occasionally, and did not use illicit drugs. His mother had colon cancer.
The physical examination was limited, because the evaluation was done in a video conference in the context of the Covid-19 pandemic. Imaging studies were obtained.
Dr. Anderson: CT of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed multiple new hypoenhancing lesions throughout the right and left hepatic lobes, diffuse small-bowel wall thickening, moderate-volume ascites, upper abdominal varices, and enlarged upper abdominal and pelvic nodes (Figure 1C, 1D, and 1E). The only liver lesions that were large enough for reliable percutaneous sampling were at the far cranial aspect of the hepatic dome, where respiratory motion and crossing the diaphragm would have made an attempt at CT-guided or ultrasonographically guided biopsy very challenging, if not prohibitive. CT of the chest revealed tree-in-bud and clustered nodules, predominantly in the dependent lower lobes, and right hilar and subcarinal lymphadenopathy (Figure 1F).
Dr. Uchida: Tests for hepatitis C virus antibodies and for hepatitis B virus surface antibodies, surface antigen, and core antibodies were negative. Repeat paracentesis was performed, and 3.2 liters of milky-appearing ascitic fluid were removed. Results of the ascitic fluid analysis are shown in Table 1. An acid-fast stain of a concentrated specimen of ascitic fluid was negative. Cytologic examination of the ascitic fluid revealed no malignant cells. A fluoroscopically guided transjugular liver biopsy was also performed. The hepatic venous pressure gradient (HVPG) was 2 mm Hg (normal value, <5); the right atrial pressure was 7 mm Hg, the wedged hepatic venous pressure 11 mm Hg, and the free hepatic venous pressure 9 mm Hg.
Dr. Megan J. Fitzpatrick: Histologic examination of the liver-biopsy specimen revealed mild mixed portal inflammation and grade 1 steatosis without steatohepatitis. A trichrome stain showed mild portal tract edema but no fibrosis.
Dr. Uchida: Mycobacterial cultures of the ascitic fluid were negative. A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 57-year-old man was evaluated in the gastroenterology clinic of this hospital because of new ascites.
Twenty years before the current presentation, the patient began to have swelling of the legs, which initially occurred only after airplane trips. During the fifth decade of life, the leg swelling was present on a daily basis. Thirteen years before the current presentation, the patient began to have frequent bowel movements (up to four per day) with loose malodorous stools and increased flatus. He was evaluated in the gastroenterology clinic of this hospital. On examination, the abdomen was soft and nontender, with no evidence of organomegaly. There was pitting edema in both legs. The blood level of total protein was 5.5 g per deciliter (reference range, 6.0 to 8.3), and the blood albumin level was 3.1 g per deciliter (reference range, 3.3 to 5.0). Results of other liver-function tests, including liver enzyme levels, were normal. The protein level in a 24-hour urine sample was normal. The blood alpha1-antitrypsin level was 173 mg per deciliter (reference value, <54). Blood levels of IgG, IgA, and IgM were low. Serologic tests for anti-tissue transglutaminase antibodies and anti-giardia antibodies were negative.
Dr. Mark A. Anderson: Computed tomographic (CT) enterography of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed diffuse mural thickening and hyperenhancement of the small bowel, with no evidence of stricturing or obstruction (Figure 1A and 1B). In addition, there was trace ascites (Figure 1B).	
Figure 1 
Dr. Uchida: Esophagogastroduodenoscopy (EGD) and colonoscopy revealed no visible abnormalities. A random biopsy specimen of the duodenum showed a focal area with more than 70 eosinophils per high-power field; a biopsy specimen of the gastric antrum showed scattered eosinophils in the lamina propria. A working diagnosis of protein-losing enteropathy was made, although neither a 2-week course of oral prednisone nor a 6-week course of oral budesonide led to a decrease in the number of bowel movements or leg edema. No further treatment was pursued.
Eleven years before the current presentation, the patient was evaluated in the gastroenterology clinic of this hospital. There had been no weight loss or recurrent infections, but leg edema persisted. Repeat EGD revealed no visible abnormalities, and a random biopsy specimen of the duodenum showed fewer eosinophils than the previous specimen, with no epithelial damage. CT enterography revealed diffuse wall thickening of the entire small bowel and trace ascites. Treatment for protein-losing enteropathy - which included limiting salt intake, increasing dietary protein, and wearing compression stockings - was recommended. During the next 10 years, the leg edema was stable and was occasionally treated with diuretic agents, which did not lead to substantial improvement.
Six months before the current presentation, the patient began to have dyspnea on exertion. Three months before this presentation, abdominal distention developed. The patient initially attributed the dyspnea and abdominal distention to weight gain due to reduced physical activity during quarantine for the coronavirus disease 2019 (Covid-19) pandemic. Six weeks before this presentation, the patient was evaluated by his primary care physician in a video conference. On the basis of this evaluation, laboratory and imaging studies were obtained. The blood level of total protein was 4.5 g per deciliter (updated reference range, 6.4 to 8.3), and the blood albumin level was 2.1 g per deciliter. The complete blood count, blood levels of electrolytes and glucose, and results of liver-function and kidney-function tests were normal.
Dr. Anderson: CT of the chest, performed after the administration of intravenous contrast material, revealed multiple small pulmonary nodules, enlarged subcarinal and upper mesenteric lymph nodes, and moderate-volume ascites in the upper abdomen.
Dr. Uchida: Three weeks later, paracentesis was performed, and 3.1 liters of milky-appearing ascitic fluid were removed. Results of the ascitic fluid analysis are shown in Table 1. Cytologic examination of the ascitic fluid revealed no malignant cells. The patient was referred to the gastroenterology clinic of this hospital for further evaluation.	
Table 1 
On the current presentation, the patient reported that he was having bowel movements with normally formed stools and no abdominal pain. His wife had noticed that he appeared to be moving slowly when performing activities of daily living and that he had lost muscle mass in his arms. There was no history of abdominal surgery or trauma to the abdomen. Other medical history included type 2 diabetes mellitus, psoriasis, osteoarthritis, and hypogammaglobulinemia. There was no history of recurrent infections, asthma, or atopic dermatitis. Medications included aspirin, insulin glargine, and metformin. There were no known drug allergies. The patient lived with his wife in a suburb of Boston and worked in an office. He was a lifelong nonsmoker, drank alcohol occasionally, and did not use illicit drugs. His mother had colon cancer.
The physical examination was limited, because the evaluation was done in a video conference in the context of the Covid-19 pandemic. Imaging studies were obtained.
Dr. Anderson: CT of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed multiple new hypoenhancing lesions throughout the right and left hepatic lobes, diffuse small-bowel wall thickening, moderate-volume ascites, upper abdominal varices, and enlarged upper abdominal and pelvic nodes (Figure 1C, 1D, and 1E). The only liver lesions that were large enough for reliable percutaneous sampling were at the far cranial aspect of the hepatic dome, where respiratory motion and crossing the diaphragm would have made an attempt at CT-guided or ultrasonographically guided biopsy very challenging, if not prohibitive. CT of the chest revealed tree-in-bud and clustered nodules, predominantly in the dependent lower lobes, and right hilar and subcarinal lymphadenopathy (Figure 1F).
Dr. Uchida: Tests for hepatitis C virus antibodies and for hepatitis B virus surface antibodies, surface antigen, and core antibodies were negative. Repeat paracentesis was performed, and 3.2 liters of milky-appearing ascitic fluid were removed. Results of the ascitic fluid analysis are shown in Table 1. An acid-fast stain of a concentrated specimen of ascitic fluid was negative. Cytologic examination of the ascitic fluid revealed no malignant cells. A fluoroscopically guided transjugular liver biopsy was also performed. The hepatic venous pressure gradient (HVPG) was 2 mm Hg (normal value, <5); the right atrial pressure was 7 mm Hg, the wedged hepatic venous pressure 11 mm Hg, and the free hepatic venous pressure 9 mm Hg.
Dr. Megan J. Fitzpatrick: Histologic examination of the liver-biopsy specimen revealed mild mixed portal inflammation and grade 1 steatosis without steatohepatitis. A trichrome stain showed mild portal tract edema but no fibrosis.
Dr. Uchida: Mycobacterial cultures of the ascitic fluid were negative. A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of leg swelling, frequent bowel movements with loose malodorous stools, and increased flatus. He also has low blood levels of total protein and albumin, which suggests protein-losing enteropathy. The patient's symptoms did not improve with corticosteroid treatment, which suggests that the protein-losing enteropathy is not due to an inflammatory condition. The patient also has new ascites, which is often associated with liver disease. However, liver function tests were normal and liver biopsy showed no fibrosis, which suggests that the ascites is not due to liver disease. The ascitic fluid was milky-appearing, which suggests chylous ascites. Chylous ascites is often due to obstruction or damage to the lymphatic system. The patient also has multiple small pulmonary nodules, enlarged lymph nodes, and diffuse small-bowel wall thickening on CT, which suggests a systemic process involving the lymphatic system. The patient's symptoms and imaging findings are consistent with lymphangiectasia, a condition characterized by dilation of the lymphatic vessels, which can cause protein-losing enteropathy and chylous ascites.\n\nDiagnosis: Lymphangiectasia""
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        ""content"": ""The patient is a 57-year-old man with a long history of leg swelling and loose, malodorous stools. He has recently developed new ascites, dyspnea on exertion, and abdominal distention. His blood tests show low total protein and albumin levels, suggesting a protein-losing enteropathy. His CT scans reveal diffuse small-bowel wall thickening, moderate-volume ascites, upper abdominal varices, and enlarged upper abdominal and pelvic nodes. The patient's history and clinical findings suggest a chronic disease process affecting his gastrointestinal system and causing protein loss. The differential diagnosis includes conditions that cause protein-losing enteropathy, such as lymphangiectasia, Whipple's disease, intestinal lymphoma, and tuberculosis. The patient's CT findings of diffuse small-bowel wall thickening and ascites are suggestive of lymphangiectasia. However, the patient's negative mycobacterial cultures and the absence of malignant cells in the ascitic fluid make tuberculosis and intestinal lymphoma less likely. Whipple's disease is also less likely given the patient's lack of weight loss and the absence of macrophages filled with periodic acid\u2013Schiff (PAS)-positive granules in the intestinal biopsy. Given these considerations, the most likely diagnosis is lymphangiectasia.\n\nDiagnosis: Lymphangiectasia.""
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10.1056/NEJMcpc2201233,"Case 13-2022: A 56-Year-Old Man with Myalgias, Fever, and Bradycardia.","Hemoglobin (g/dl)   13.1 9.9   9.8
Hematocrit (%) 39.0–51.0 39.2 29.7   29.3
White-cell count (per μl)   4000 8600   8800
Differential count (per μl)
Neutrophils 180 000 2100 6300   6470
Lymphocytes   1500 1200   1250
Monocytes 220–660 200 1100   990
Eosinophils 0–600 100 0   20
Platelet count (per μl)   140,000 229,000   210,000
Sodium (mmol/liter) 134–146 133 136   132
Potassium (mmol/liter) 3.3–5.3 4.3 4.3   4.4
Chloride (mmol/liter) 98–110 98 103 98–110 99
Carbon dioxide (mmol/liter) 21–33 25 29   24
Urea nitrogen (mg/dl) 7–25 19 16   17
Creatinine (mg/dl) 0.50–1.40 1.49 1.32   1.26
Glucose (mg/dl) 6 9 86 127   105
d-dimer (ng/ml) <499 — 983 — —
Albumin (g/dl)   — 3.3   3.5
Globulin (g/dl) — — —   4.8
Erythrocyte sedimentation rate (mm/hr) <15 — 29   89
C-reactive protein (mg/liter)  .0 — 178.8  .0 226.0
High-sensitivity troponin T (ng/liter) — — — 0–9 53",Regional myocarditis due to infection with Listeria monocytogenes.,Regional myocarditis due to infection with Listeria monocytogenes.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 56-year-old man presented to this hospital in early autumn with a 1-month history of myalgias and fever.
Approximately 4 weeks before the current presentation, the patient began to have generalized myalgias and arthralgias, which were worst in the shoulders, proximal arms, and upper back. He had fever with temperatures of up to 38.2[degrees]C, along with chills and diaphoresis. He took naproxen, and the next day, he presented to an urgent care clinic affiliated with this hospital. The temperature was 37.2[degrees]C, the heart rate 72 beats per minute, the blood pressure 175/95 mm Hg, and the oxygen saturation 100% while he was breathing ambient air; the remainder of the physical examination was normal. A test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative. Symptoms abated after 3 days, but then fever with temperatures of up to 38.3[degrees]C and fatigue occurred. The patient stopped consuming alcohol.
Three weeks later, the patient had episodes of mild dyspnea with ""coughing fits"" and presented to a second urgent care clinic affiliated with this hospital. The temperature was 37.2[degrees]C, the heart rate 59 beats per minute, the blood pressure 138/75 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. He appeared fatigued, but the remainder of the physical examination was normal. Another test for SARS-CoV-2 RNA was negative, and the results of urinalysis and chest radiography were normal.
The next day, the patient was evaluated by his primary care physician at another hospital. He reported a 1-month history of ""stabbing"" back pain between his shoulders, which was worst at the end of the day and was not relieved with the use of naproxen or a heating pad. The temperature was 36.7[degrees]C, the heart rate 48 beats per minute, the blood pressure 122/72 mm Hg, and the oxygen saturation 100% while he was breathing ambient air. There was tenderness on palpation of the left thoracic paraspinal area, but the remainder of the physical examination was normal. Radiographic images of the thoracic spine were reportedly normal. Laboratory test results obtained at that time are shown in Table 1, alongside routine test results obtained 6 months earlier. The patient was referred to the emergency department of this hospital.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
On the systems review, the patient reported that he had recently measured heart rates of 40 to 50 beats per minute on his home pulse oximeter; his baseline heart rate was 80 to 90 beats per minute. He also reported a history of dysuria that was attributed to chronic prostatitis, as well as pain in the left wrist and knee that was attributed to gout. He reported no weight loss, sweats, palpitations, dyspnea, dizziness, lightheadedness, chest discomfort, joint swelling or redness, rash, headache, focal neurologic symptoms, nausea, vomiting, diarrhea, or rectal bleeding.
The patient's medical history was notable for sickle cell trait, hypertension with mild left ventricular hypertrophy, palpitations, unprovoked pulmonary embolism, obstructive sleep apnea, hyperuricemia, latent tuberculosis, malaria, chronic hepatitis B virus infection, Helicobacter pylori infection, colonic schistosomiasis, prostatism, and thrombocytopenia. His last dental procedure had taken place more than 2 years earlier. Medications included aspirin, metoprolol, and losartan, as well as sildenafil as needed. He had received two vaccines for coronavirus disease 2019 (Covid-19), with the second vaccine administered 7 months before the current evaluation. There were no known adverse reactions to medication.
The patient grew up in equatorial Central Africa. He had immigrated to the United States 20 years earlier and had not returned to Africa for more than 5 years. He was employed at a local university and occasionally had contact with college students. He lived with his family in a suburb of Boston. During the summer months, he had visited islands in Massachusetts and coastal wooded areas to hike, camp, and swim. The patient reported that he had encountered many ticks but had not received a tick bite. He had been scratched by cats; there were no other animal exposures. In the past, he had consumed two or three beers daily, but he had stopped all alcohol intake during the previous month. He had never used tobacco or illicit substances. His family history was notable for atherosclerotic coronary disease.
On examination, the temperature was 36.5[degrees]C, the heart rate 46 beats per minute, the blood pressure 141/65 mm Hg, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.4. He appeared comfortable. Auscultation of the chest revealed a bradycardic heart rate. There was tenderness on palpation of the left infrascapular area. A prostate examination revealed a nontender hemorrhoid. There was no rash or lymphadenopathy, and the remainder of the examination was normal.
Blood levels of calcium, total protein, and thyrotropin were normal, as were the results of liver-function tests. Other laboratory test results are shown in Table 1. Blood cultures were obtained. Electrocardiograms were notable for sinus rhythm with first-degree and second-degree (2:1) atrioventricular block with intermittent right bundle-branch block (Figure 1A), alternating with sinus rhythm with third-degree (complete) atrioventricular block and junctional escape rhythm with intraventricular conduction delay (Figure 1B). Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, was negative for pulmonary embolism.	
Figure 1 
Intravenous ceftriaxone, naproxen, acetaminophen, and oxycodone were administered. The patient was evaluated by an electrophysiologist and admitted to the cardiology unit of this hospital. The next day, the heart rate remained at approximately 40 beats per minute, and the maximum temperature was 37.8[degrees]C. Oxycodone and topical lidocaine were administered.
Dr. Alex L. Huang: Transthoracic echocardiography (TTE) revealed normal biventricular systolic function, with no regional left ventricular wall-motion abnormalities. There was mild diastolic mitral and tricuspid regurgitation (Figure 1C), a finding consistent with atrioventricular block.1 There was no evidence of valvular vegetations.
Dr. Khurshid: The blood level of high-sensitivity troponin was 63 ng per liter. Urinalysis was negative, as were blood tests for Lyme disease antibodies, anti-rickettsia IgM, ehrlichia and anaplasma DNA, human immunodeficiency virus types 1 and 2, and babesia.
On the third hospital day, tests for SARS-CoV-2, Bartonella henselae and B. quintana antibodies, and anti-treponemal antibodies were negative. An interferon-[gamma] release assay for Mycobacterium tuberculosis was positive.
Dr. Borek Foldyna: The patient underwent cardiac CT with electrocardiographic gating, including contrast-enhanced CT angiography and delayed imaging. Epicardial fat and a thickened interatrial septum abutting the noncoronary sinus of the aortic valve showed increased radiodensity on delayed imaging (Figure 2A and 2B); these findings are suggestive of inflammatory changes and may indicate evolving abscess. The tricuspid aortic valve had mildly thickened leaflets, but there was no evidence of focal valvular vegetations, thrombi, or calcifications.	
Figure 2  
Dr. Khurshid: Oral doxycycline was administered. On the fourth hospital day, the ventricular rate measured between 30 and 40 beats per minute, and the maximum temperature was 37.9[degrees]C
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 56-year-old man presented to this hospital in early autumn with a 1-month history of myalgias and fever.
Approximately 4 weeks before the current presentation, the patient began to have generalized myalgias and arthralgias, which were worst in the shoulders, proximal arms, and upper back. He had fever with temperatures of up to 38.2[degrees]C, along with chills and diaphoresis. He took naproxen, and the next day, he presented to an urgent care clinic affiliated with this hospital. The temperature was 37.2[degrees]C, the heart rate 72 beats per minute, the blood pressure 175/95 mm Hg, and the oxygen saturation 100% while he was breathing ambient air; the remainder of the physical examination was normal. A test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative. Symptoms abated after 3 days, but then fever with temperatures of up to 38.3[degrees]C and fatigue occurred. The patient stopped consuming alcohol.
Three weeks later, the patient had episodes of mild dyspnea with ""coughing fits"" and presented to a second urgent care clinic affiliated with this hospital. The temperature was 37.2[degrees]C, the heart rate 59 beats per minute, the blood pressure 138/75 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. He appeared fatigued, but the remainder of the physical examination was normal. Another test for SARS-CoV-2 RNA was negative, and the results of urinalysis and chest radiography were normal.
The next day, the patient was evaluated by his primary care physician at another hospital. He reported a 1-month history of ""stabbing"" back pain between his shoulders, which was worst at the end of the day and was not relieved with the use of naproxen or a heating pad. The temperature was 36.7[degrees]C, the heart rate 48 beats per minute, the blood pressure 122/72 mm Hg, and the oxygen saturation 100% while he was breathing ambient air. There was tenderness on palpation of the left thoracic paraspinal area, but the remainder of the physical examination was normal. Radiographic images of the thoracic spine were reportedly normal. Laboratory test results obtained at that time are shown in Table 1, alongside routine test results obtained 6 months earlier. The patient was referred to the emergency department of this hospital.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
On the systems review, the patient reported that he had recently measured heart rates of 40 to 50 beats per minute on his home pulse oximeter; his baseline heart rate was 80 to 90 beats per minute. He also reported a history of dysuria that was attributed to chronic prostatitis, as well as pain in the left wrist and knee that was attributed to gout. He reported no weight loss, sweats, palpitations, dyspnea, dizziness, lightheadedness, chest discomfort, joint swelling or redness, rash, headache, focal neurologic symptoms, nausea, vomiting, diarrhea, or rectal bleeding.
The patient's medical history was notable for sickle cell trait, hypertension with mild left ventricular hypertrophy, palpitations, unprovoked pulmonary embolism, obstructive sleep apnea, hyperuricemia, latent tuberculosis, malaria, chronic hepatitis B virus infection, Helicobacter pylori infection, colonic schistosomiasis, prostatism, and thrombocytopenia. His last dental procedure had taken place more than 2 years earlier. Medications included aspirin, metoprolol, and losartan, as well as sildenafil as needed. He had received two vaccines for coronavirus disease 2019 (Covid-19), with the second vaccine administered 7 months before the current evaluation. There were no known adverse reactions to medication.
The patient grew up in equatorial Central Africa. He had immigrated to the United States 20 years earlier and had not returned to Africa for more than 5 years. He was employed at a local university and occasionally had contact with college students. He lived with his family in a suburb of Boston. During the summer months, he had visited islands in Massachusetts and coastal wooded areas to hike, camp, and swim. The patient reported that he had encountered many ticks but had not received a tick bite. He had been scratched by cats; there were no other animal exposures. In the past, he had consumed two or three beers daily, but he had stopped all alcohol intake during the previous month. He had never used tobacco or illicit substances. His family history was notable for atherosclerotic coronary disease.
On examination, the temperature was 36.5[degrees]C, the heart rate 46 beats per minute, the blood pressure 141/65 mm Hg, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.4. He appeared comfortable. Auscultation of the chest revealed a bradycardic heart rate. There was tenderness on palpation of the left infrascapular area. A prostate examination revealed a nontender hemorrhoid. There was no rash or lymphadenopathy, and the remainder of the examination was normal.
Blood levels of calcium, total protein, and thyrotropin were normal, as were the results of liver-function tests. Other laboratory test results are shown in Table 1. Blood cultures were obtained. Electrocardiograms were notable for sinus rhythm with first-degree and second-degree (2:1) atrioventricular block with intermittent right bundle-branch block (Figure 1A), alternating with sinus rhythm with third-degree (complete) atrioventricular block and junctional escape rhythm with intraventricular conduction delay (Figure 1B). Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, was negative for pulmonary embolism.	
Figure 1 
Intravenous ceftriaxone, naproxen, acetaminophen, and oxycodone were administered. The patient was evaluated by an electrophysiologist and admitted to the cardiology unit of this hospital. The next day, the heart rate remained at approximately 40 beats per minute, and the maximum temperature was 37.8[degrees]C. Oxycodone and topical lidocaine were administered.
Dr. Alex L. Huang: Transthoracic echocardiography (TTE) revealed normal biventricular systolic function, with no regional left ventricular wall-motion abnormalities. There was mild diastolic mitral and tricuspid regurgitation (Figure 1C), a finding consistent with atrioventricular block.1 There was no evidence of valvular vegetations.
Dr. Khurshid: The blood level of high-sensitivity troponin was 63 ng per liter. Urinalysis was negative, as were blood tests for Lyme disease antibodies, anti-rickettsia IgM, ehrlichia and anaplasma DNA, human immunodeficiency virus types 1 and 2, and babesia.
On the third hospital day, tests for SARS-CoV-2, Bartonella henselae and B. quintana antibodies, and anti-treponemal antibodies were negative. An interferon-[gamma] release assay for Mycobacterium tuberculosis was positive.
Dr. Borek Foldyna: The patient underwent cardiac CT with electrocardiographic gating, including contrast-enhanced CT angiography and delayed imaging. Epicardial fat and a thickened interatrial septum abutting the noncoronary sinus of the aortic valve showed increased radiodensity on delayed imaging (Figure 2A and 2B); these findings are suggestive of inflammatory changes and may indicate evolving abscess. The tricuspid aortic valve had mildly thickened leaflets, but there was no evidence of focal valvular vegetations, thrombi, or calcifications.	
Figure 2  
Dr. Khurshid: Oral doxycycline was administered. On the fourth hospital day, the ventricular rate measured between 30 and 40 beats per minute, and the maximum temperature was 37.9[degrees]C
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Lyme Disease. The patient's history of hiking and camping in wooded areas, along with his symptoms of fever, myalgias, and arthralgias, suggest a tick-borne illness. Although he reported no known tick bites, many patients with Lyme disease do not recall a tick bite. His cardiac symptoms, including bradycardia and varying degrees of heart block, are consistent with Lyme carditis, a complication of Lyme disease. His negative tests for Lyme disease antibodies are not definitive, as serologic tests can be negative in the early stages of the disease. The administration of ceftriaxone and doxycycline, antibiotics effective against the bacterium that causes Lyme disease, further supports this diagnosis.""
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        ""content"": ""The patient is a 56-year-old man with a history of hypertension, pulmonary embolism, and chronic hepatitis B infection, who presents with a 1-month history of myalgias, arthralgias, fever, fatigue, and back pain. He also has bradycardia and a history of exposure to ticks. The differential diagnosis includes Lyme disease, babesiosis, ehrlichiosis, anaplasmosis, and other tick-borne diseases, as well as viral infections, rheumatologic conditions, and endocarditis. However, the patient's tests for Lyme disease, babesiosis, ehrlichiosis, and anaplasmosis were negative. His symptoms do not fit well with a viral infection or a rheumatologic condition. The patient's bradycardia, fever, and back pain, along with the echocardiogram findings of mild diastolic mitral and tricuspid regurgitation and the CT findings suggestive of inflammatory changes and possible evolving abscess, raise the suspicion for endocarditis. The patient's history of chronic hepatitis B infection could potentially predispose him to endocarditis. \n\nDiagnosis: Endocarditis.""
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10.1056/NEJMcpc2115855,Case 12-2022: A 41-Year-Old Woman with Transient Ischemic Attack and Mitral Valve Masses,"Hemoglobin (g/dl) 12. .9 6.7 8.5 9.2   8.4
Hematocrit (%) 34.9–44.5 20.3 25.3 27.4   26.6
Mean corpuscular volume (fl)   64.1 67.1 68.2   71.9
White-cell count (per μl) 400 ,000 5320 5160 6680   5800
Platelet count (per μl) 135,00 0,000 168,000 156,000 172,000   151,000
Prothrombin time (sec)   — 14.4 13.4   —
International normalized 
ratio
  — 1.1 1.2   —
Partial-thromboplastin time 
(sec)
22. 6.0 — 39.0 >150.0 22. 6.0 —
Fibrinogen (mg/dl) 20 0 — — 311 — —
d-dimer (ng/ml)   — — 566 — —
Anti–factor Xa (IU/ml) Not detected Not detected — —  1 0.13
High-sensitivity troponin T 
(ng/liter)
0–9 — 12 — — —
Erythrocyte sedimentation 
rate (mm/hr)
 0 — 48 —   —
C-reactive protein (mg/liter) 0. .0 — 6.1 — — —
CA-125 (U/ml)  5 — 14 — — —
Carcinoembryonic antigen 
(ng/ml)
<5.3 — 1.5 — — —
Iron (μg/dl) 50–170 — 68 — 30–160 —
Total iron-binding capacity 
(μg/dl)
250–450 — 427 — 23 4 —
Ferritin (≈í¬∫g/liter) 1 91 ‚Äö√Ñ√Æ 13 ‚Äö√Ñ√Æ 1 00 ‚Äö√Ñ√Æ",Systemic lupus erythematosus with antiphospholipid syndrome,Systemic lupus erythematosus.  Libman–Sacks endocarditis with associated antiphospholipid syndrome and systemic lupus erythematosus.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 41-year-old woman with transient dysarthria and facial droop was transferred to this hospital for evaluation of masses on the mitral valve.
Three weeks before this presentation, the patient presented to the emergency department of another hospital because of concerns about heavy vaginal bleeding that had developed 1 week earlier and was associated with crampy abdominal pain, fatigue, dyspnea, and lightheadedness. Examination was notable for a heart rate of 91 beats per minute, a blood pressure of 130/79 mm Hg, and an oxygen saturation of 100% while she was breathing ambient air; the examination was otherwise reportedly normal, although a gynecologic examination was not performed. Laboratory results were notable for a hemoglobin level of 8.2 g per deciliter (reference range, 12.0 to 16.0; previous level 1 year earlier, 9.1), a mean corpuscular volume of 71.3 fl (reference range, 80 to 94), and a platelet count of 148,000 per microliter (reference range, 150,000 to 450,000). Urine human chorionic gonadotropin was undetectable. Normal saline was administered intravenously, and a 5-day course of medroxyprogesterone acetate was prescribed.
Eleven days after the patient completed the therapy with medroxyprogesterone acetate (9 days before this presentation), heavy vaginal bleeding and dyspnea recurred. An additional 3-day course of medroxyprogesterone acetate was prescribed. The evening after the patient finished the second course of treatment, within 1 hour after she had been seen and had appeared to be well, her husband noted that she had facial droop on the right side and slurred speech; he called emergency medical services. When she arrived at the emergency department of a second hospital, within 1 hour after the onset of symptoms, her examination was notable for a heart rate of 91 beats per minute, a blood pressure of 173/83 mm Hg, and an oxygen saturation of 99% while she was breathing ambient air. She was noted to have facial droop on the right side and unintelligible speech.
Dr. Sandra P. Rincon: Computed tomography (CT) of the head (Figure 1A) revealed no evidence of acute infarction or intracranial hemorrhage. Small chronic infarcts were seen in the right thalamus and right cerebellar hemisphere. A CT angiogram (CTA) of the head and neck did not show high-grade stenosis or large-vessel occlusion.	
Figure 1 
Dr. Nestor: A neurology consultation was obtained; aspirin and atorvastatin were administered. Blood levels of electrolytes, albumin, low-density lipoprotein cholesterol, and glycated hemoglobin were normal, as were the white-cell count and differential count and the results of liver-function and kidney-function tests. Urine human chorionic gonadotropin was undetectable, and urinalysis showed 3+ blood, no protein, and no casts. Additional laboratory test results are shown in Table 1. Within 45 minutes after the patient arrived at the emergency department of the second hospital, the facial asymmetry and dysarthria resolved. The patient was admitted to the medical unit of the second hospital.	
Table 1 
Dr. Rincon: The next day, magnetic resonance imaging (MRI) and angiography of the head and neck again revealed old lacunar infarcts in the right thalamus (Figure 1B) and right cerebellar hemisphere (Figure 1C). There was no evidence of an acute infarction (Figure 1D), intracranial hemorrhage, or cerebrovascular occlusion (Figure 1E and 1F).
Dr. Nestor: Two units of packed red cells were transfused. Post-transfusion laboratory test results are shown in Table 1. A transthoracic echocardiogram (Figure 2A and 2B and Video 1, available with the full text of this article at
NEJM.org
) showed thickened mitral valve leaflets and mild-to-moderate mitral regurgitation, with an estimated right ventricular systolic pressure of 48 mm Hg.	
Figure 2 
Dr. Evin Yucel: On the third hospital day, a transesophageal echocardiogram (Figure 2C and Videos 2 and 3) showed multiple echodensities on the atrial side of the mitral valve leaflets at the closure lines that were consistent with vegetations. Cultures of blood were obtained, and heparin was administered intravenously.
Dr. Nestor: On the fourth hospital day, the rate of heparin infusion was decreased at 6-hour intervals when the partial-thromboplastin time exceeded 150 seconds, until the infusion was stopped. Laboratory test results are shown in Table 1; complement levels (C3 and C4) were normal. Additional cultures of blood were obtained.
Dr. Rincon: Repeat CT of the head revealed no acute abnormality. CT of the chest showed clustered nodules in the lower lobes that were probably related to aspiration, and CT of the abdomen and pelvis (Figure 2D, 2E, and 2F) revealed an enlarged heterogeneous uterus with multiple fibroids.
Dr. Nestor: The next day, the patient was transferred to this hospital. On a review of systems, she reported no recurrence of dysarthria or facial droop and noted no other neurologic symptoms. She reported that she had had heavy menstrual bleeding and exertional dyspnea in the weeks preceding this presentation; pruritic, macular rashes on the trunk, scalp, arms, and legs with associated photosensitivity that had persisted for many weeks; new Raynaud's phenomenon in the past 10 months; and a long history of dry eyes and seasonal allergies. Medical history was notable for sickle cell trait, vitamin B12 deficiency, iron deficiency resulting in past iron infusions, uterine fibroids, anxiety, and hypertension. Surgical history included multiple laparoscopies and two laparotomies, including salpingo-oophorectomy for endometriosis. Owing to infertility, she had undergone in vitro fertilization; she had a first-trimester spontaneous abortion at 25 years of age. During her second pregnancy at 33 years of age, a screening rapid plasma reagin (RPR) test was positive at 1:8; however, a treponemal-specific confirmatory test for syphilis was negative. Pregnancy-induced hypertension developed, followed by placental abruption at 30 weeks, which resulted in a cesarean delivery. Medications included amlodipine, cyanocobalamin, ferrous sulfate, and medroxyprogesterone acetate. She had no known medication allergies.
The patient lived in eastern Massachusetts with her husband and child. She did not drink alcohol or smoke tobacco. Her mother had rheumatoid arthritis, hypertension, and a history of spontaneous abortion. One grandmother had diabetes and the other grandmother had had a stroke. An aunt had had leukemia and later breast cancer. Her child has psoriasis.
The temperature was 36.8[degrees]C, the heart rate 74 beats per minute, the blood pressure 155/98 mm Hg, and the oxygen saturation 99% while the patient was breathing ambient air. The height was 175 cm, the weight 107 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 34.9. There were several small, circular macules on her back (Figure 3). There was a grade 2/6 holosystolic murmur at the left sternal border and apex. She had no lymphadenopathy, petechiae, nail changes, or evidence of arthritis. The remainder of the examination was normal, as was a neurologic examination.	
Figure 3 
Laboratory test results are shown in Table 1. All the blood cultures obtained at the second hospital showed no growth. An electrocardiogram was normal.
Diagnostic test results were received, and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 41-year-old woman with transient dysarthria and facial droop was transferred to this hospital for evaluation of masses on the mitral valve.
Three weeks before this presentation, the patient presented to the emergency department of another hospital because of concerns about heavy vaginal bleeding that had developed 1 week earlier and was associated with crampy abdominal pain, fatigue, dyspnea, and lightheadedness. Examination was notable for a heart rate of 91 beats per minute, a blood pressure of 130/79 mm Hg, and an oxygen saturation of 100% while she was breathing ambient air; the examination was otherwise reportedly normal, although a gynecologic examination was not performed. Laboratory results were notable for a hemoglobin level of 8.2 g per deciliter (reference range, 12.0 to 16.0; previous level 1 year earlier, 9.1), a mean corpuscular volume of 71.3 fl (reference range, 80 to 94), and a platelet count of 148,000 per microliter (reference range, 150,000 to 450,000). Urine human chorionic gonadotropin was undetectable. Normal saline was administered intravenously, and a 5-day course of medroxyprogesterone acetate was prescribed.
Eleven days after the patient completed the therapy with medroxyprogesterone acetate (9 days before this presentation), heavy vaginal bleeding and dyspnea recurred. An additional 3-day course of medroxyprogesterone acetate was prescribed. The evening after the patient finished the second course of treatment, within 1 hour after she had been seen and had appeared to be well, her husband noted that she had facial droop on the right side and slurred speech; he called emergency medical services. When she arrived at the emergency department of a second hospital, within 1 hour after the onset of symptoms, her examination was notable for a heart rate of 91 beats per minute, a blood pressure of 173/83 mm Hg, and an oxygen saturation of 99% while she was breathing ambient air. She was noted to have facial droop on the right side and unintelligible speech.
Dr. Sandra P. Rincon: Computed tomography (CT) of the head (Figure 1A) revealed no evidence of acute infarction or intracranial hemorrhage. Small chronic infarcts were seen in the right thalamus and right cerebellar hemisphere. A CT angiogram (CTA) of the head and neck did not show high-grade stenosis or large-vessel occlusion.	
Figure 1 
Dr. Nestor: A neurology consultation was obtained; aspirin and atorvastatin were administered. Blood levels of electrolytes, albumin, low-density lipoprotein cholesterol, and glycated hemoglobin were normal, as were the white-cell count and differential count and the results of liver-function and kidney-function tests. Urine human chorionic gonadotropin was undetectable, and urinalysis showed 3+ blood, no protein, and no casts. Additional laboratory test results are shown in Table 1. Within 45 minutes after the patient arrived at the emergency department of the second hospital, the facial asymmetry and dysarthria resolved. The patient was admitted to the medical unit of the second hospital.	
Table 1 
Dr. Rincon: The next day, magnetic resonance imaging (MRI) and angiography of the head and neck again revealed old lacunar infarcts in the right thalamus (Figure 1B) and right cerebellar hemisphere (Figure 1C). There was no evidence of an acute infarction (Figure 1D), intracranial hemorrhage, or cerebrovascular occlusion (Figure 1E and 1F).
Dr. Nestor: Two units of packed red cells were transfused. Post-transfusion laboratory test results are shown in Table 1. A transthoracic echocardiogram (Figure 2A and 2B and Video 1, available with the full text of this article at
NEJM.org
) showed thickened mitral valve leaflets and mild-to-moderate mitral regurgitation, with an estimated right ventricular systolic pressure of 48 mm Hg.	
Figure 2 
Dr. Evin Yucel: On the third hospital day, a transesophageal echocardiogram (Figure 2C and Videos 2 and 3) showed multiple echodensities on the atrial side of the mitral valve leaflets at the closure lines that were consistent with vegetations. Cultures of blood were obtained, and heparin was administered intravenously.
Dr. Nestor: On the fourth hospital day, the rate of heparin infusion was decreased at 6-hour intervals when the partial-thromboplastin time exceeded 150 seconds, until the infusion was stopped. Laboratory test results are shown in Table 1; complement levels (C3 and C4) were normal. Additional cultures of blood were obtained.
Dr. Rincon: Repeat CT of the head revealed no acute abnormality. CT of the chest showed clustered nodules in the lower lobes that were probably related to aspiration, and CT of the abdomen and pelvis (Figure 2D, 2E, and 2F) revealed an enlarged heterogeneous uterus with multiple fibroids.
Dr. Nestor: The next day, the patient was transferred to this hospital. On a review of systems, she reported no recurrence of dysarthria or facial droop and noted no other neurologic symptoms. She reported that she had had heavy menstrual bleeding and exertional dyspnea in the weeks preceding this presentation; pruritic, macular rashes on the trunk, scalp, arms, and legs with associated photosensitivity that had persisted for many weeks; new Raynaud's phenomenon in the past 10 months; and a long history of dry eyes and seasonal allergies. Medical history was notable for sickle cell trait, vitamin B12 deficiency, iron deficiency resulting in past iron infusions, uterine fibroids, anxiety, and hypertension. Surgical history included multiple laparoscopies and two laparotomies, including salpingo-oophorectomy for endometriosis. Owing to infertility, she had undergone in vitro fertilization; she had a first-trimester spontaneous abortion at 25 years of age. During her second pregnancy at 33 years of age, a screening rapid plasma reagin (RPR) test was positive at 1:8; however, a treponemal-specific confirmatory test for syphilis was negative. Pregnancy-induced hypertension developed, followed by placental abruption at 30 weeks, which resulted in a cesarean delivery. Medications included amlodipine, cyanocobalamin, ferrous sulfate, and medroxyprogesterone acetate. She had no known medication allergies.
The patient lived in eastern Massachusetts with her husband and child. She did not drink alcohol or smoke tobacco. Her mother had rheumatoid arthritis, hypertension, and a history of spontaneous abortion. One grandmother had diabetes and the other grandmother had had a stroke. An aunt had had leukemia and later breast cancer. Her child has psoriasis.
The temperature was 36.8[degrees]C, the heart rate 74 beats per minute, the blood pressure 155/98 mm Hg, and the oxygen saturation 99% while the patient was breathing ambient air. The height was 175 cm, the weight 107 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 34.9. There were several small, circular macules on her back (Figure 3). There was a grade 2/6 holosystolic murmur at the left sternal border and apex. She had no lymphadenopathy, petechiae, nail changes, or evidence of arthritis. The remainder of the examination was normal, as was a neurologic examination.	
Figure 3 
Laboratory test results are shown in Table 1. All the blood cultures obtained at the second hospital showed no growth. An electrocardiogram was normal.
Diagnostic test results were received, and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms include transient dysarthria and facial droop, heavy vaginal bleeding, fatigue, dyspnea, and lightheadedness. She also has a history of sickle cell trait, vitamin B12 deficiency, iron deficiency, uterine fibroids, anxiety, and hypertension. The patient also reported pruritic, macular rashes on the trunk, scalp, arms, and legs with associated photosensitivity, new Raynaud's phenomenon, and a long history of dry eyes and seasonal allergies. These symptoms suggest an autoimmune disorder. The presence of vegetations on the mitral valve leaflets is indicative of endocarditis. The patient's history of heavy menstrual bleeding and the presence of multiple fibroids in the uterus could be the cause of her anemia. The patient's history of a positive RPR test, although the confirmatory test for syphilis was negative, suggests the possibility of a false positive result due to an autoimmune disorder. The patient's mother had rheumatoid arthritis, which is also an autoimmune disorder. Given these findings, the patient's symptoms are most likely due to an autoimmune disorder, specifically systemic lupus erythematosus (SLE), which can cause a wide range of symptoms, including those experienced by the patient. The presence of endocarditis could be due to Libman-Sacks endocarditis, which is associated with SLE.\n\nDiagnosis: Systemic Lupus Erythematosus with Libman-Sacks Endocarditis.""
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        ""content"": ""The patient is a 41-year-old woman who presents with transient dysarthria and facial droop, heavy vaginal bleeding, and masses on the mitral valve. The differential diagnosis for this patient includes endocarditis, systemic lupus erythematosus (SLE), antiphospholipid syndrome, and malignancy. The patient's heavy vaginal bleeding and enlarged heterogeneous uterus with multiple fibroids suggest a gynecological issue, but this does not explain the masses on the mitral valve or the transient neurological symptoms. Endocarditis could explain the masses on the mitral valve and the transient neurological symptoms, but the patient's blood cultures were negative, making this diagnosis less likely. The patient's history of photosensitive rashes, Raynaud's phenomenon, and dry eyes, along with the presence of vegetations on the mitral valve and transient neurological symptoms, are suggestive of SLE. However, the patient's complement levels were normal, which is not typical in active SLE. The patient's history of a spontaneous abortion, pregnancy-induced hypertension, and placental abruption, along with the transient neurological symptoms and vegetations on the mitral valve, are suggestive of antiphospholipid syndrome. This condition is associated with thrombotic events, which could explain the patient's transient neurological symptoms and the vegetations on the mitral valve. Malignancy could potentially explain the patient's symptoms, but there is no evidence of malignancy on imaging.\n\nDiagnosis: Antiphospholipid syndrome.""
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10.1056/NEJMcpc2201232,Case 11-2022: An 80-Year-Old Woman with Pancytopenia,"Hematocrit (%) 37.0–47.0 33.7 24.8 24.8 24.3   24.8
Hemoglobin (g/dl)   10.2 8.2 7.8 7.8   7.5
White-cell count (per μl) 4800–10,800 8100 2700 3300 3100   2740
Differential count (%)
Neutrophils 40–74 52 55 48 —   21
Lymphocytes 19–48 30 26 44 —   72
Monocytes 3–9 4 8 1 —   4
Eosinophils 0–7 2 0 0 —   1
Basophils 0–1 0 0 0 —   1
Bands 0–7 11 9 7 — 0–10 6
Platelet count (per μl)   112,000 57,000 28,000 37,000   43,000
Mean corpuscular volume (fl) 79.0–97.0 — 79.7 85.2 85.0   87.3
Red-cell distribution width (%)   — 26 22.3 22.7   23.1
Reticulocyte count (%) 0.5–1.5 — — 1.9 1.8 0.7–2.5 3.0
Prothrombin time (sec) 9.4–12.3 — — 12.3 —   14.8
Prothrombin-time international normalized 
ratio
  — — 1.16 —   1.2
Activated partial-thromboplastin time (sec) 23.6–32.9 — — No clot formed — 22. 6.0 34.7
Fibrinogen (mg/dl) 186–458 — — 371 — 15 0 232
d-dimer (ng/ml) — — — — —   1166
Haptoglobin (mg/dl) 3 00 — 246 280 202 3 00 113
Lactate dehydrogenase (U/liter) 84–246 — 497 453 342 11 10 326
Ferritin (μg/liter)  2 — — 1340 — 1 00 564
Bilirubin (mg/dl)†
Total 0.2–1.0 — 1.1 1.7 1.3  0.7
Direct 0.0–0.2 — — 0.9 0.6 0.  0.2
Albumin (g/dl)   — — 1.8 2.3   3.2",Myelodysplastic syndrome.,Myelodysplastic syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 80-year-old woman was admitted to this hospital because of pancytopenia and the identification of schistocytes on a peripheral-blood smear.
Six weeks before admission to this hospital, nausea, vomiting, and diarrhea developed, along with chills and subjective fever. The symptoms resolved after 4 days without specific intervention, but then intermittent dysphagia with solid foods and early satiety developed. During the next 4 weeks, the patient had gradually progressive fatigue and light-headedness. The fatigue progressed to the point that she could no longer stay at work for more than a few hours; she presented to another hospital for evaluation.
At the other hospital, the patient reported that she had ongoing fatigue and had lost 6 kg of weight over a 5-week period. On examination, the temperature was 38.9[degrees]C, the weight 55.5 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.9. Laboratory studies revealed pancytopenia, and examination of a peripheral-blood smear revealed schistocytes. Blood levels of glucose and electrolytes were normal, as were the results of kidney-function and liver-function tests; other laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
Dr. Ranjodh S. Dhami: A chest radiograph was normal. Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed a small hiatal hernia, multiple simple cysts in the right kidney, and indeterminate bilateral pelvic masses measuring 4.8 cm in diameter on the right side and 6.3 cm in diameter on the left side (Figure 1).	
Figure 1 
Dr. Pappas: Intravenous fluids were administered, and the patient was admitted to the other hospital. On hospital day 2, the hemoglobin level decreased to 6.6 g per deciliter, and two units of packed red cells were transfused. Esophagogastroduodenoscopy revealed diffuse esophageal inflammation with white exudates throughout the esophagus; examination of brushings revealed yeast consistent with candida, and treatment with fluconazole was initiated.
During the next 3 hospital days, the patient continued to feel unwell, with persistent fever and limited oral intake due to odynophagia, and the administration of intravenous fluids was continued. Blood and urine cultures showed no growth. On hospital day 5, empirical therapy with doxycycline was started because of concerns about a possible tickborne illness.
On hospital day 6, the oxygen saturation decreased to 89% while the patient was breathing ambient air and then increased to 94% when oxygen was delivered through a nasal cannula at a rate of 3 liters per minute. CT of the chest, performed after the administration of intravenous contrast material, revealed ground-glass opacities and interlobular septal thickening, findings consistent with pulmonary edema, along with bilateral pleural effusions of a small to moderate size. The administration of intravenous fluids was stopped, and one dose of intravenous furosemide was provided.
On hospital day 7, fever resolved but pancytopenia persisted. Examination of a peripheral-blood smear revealed a moderate amount of schistocytes, severe anisocytosis, large platelets, and an increased amount of bands without blasts. Direct and indirect Coombs' tests were negative, as were nucleic acid tests for babesiosis and anaplasmosis. Blood levels of electrolytes, glucose, cobalamin, folate, homocysteine, and anticardiolipin IgG and IgM were normal, as were the results of kidney-function and liver-function tests. The results of serologic tests for Epstein-Barr virus were consistent with previous infection. Flow cytometry of the peripheral blood showed phenotypically normal myeloid cells; there was an increased amount of atypical CD34+ myeloblasts, which accounted for less than 1% of leukocytes and were of unclear clinical significance.
A tunneled catheter was placed in the right internal jugular vein, and plasma exchange was initiated for the treatment of possible thrombotic thrombocytopenic purpura (TTP). Total parenteral nutrition was also initiated, because oral intake was still limited by odynophagia.
On hospital day 8, oral intake of soft foods and liquids increased. A transthoracic echocardiogram showed normal left ventricular size and function, as well as a mildly thickened aortic valve with no stenosis or regurgitation; there was trace mitral and tricuspid regurgitation. On hospital day 9, the patient underwent additional plasma exchange and was transferred to this hospital for further care.
On evaluation in this hospital, the patient reported that her energy level had increased. She recalled that she had felt mildly confused at the other hospital, but the confusion had since resolved. She had had no gum bleeding or blood in the stool or urine. Other medical history included hypertension and dyslipidemia. Surgical history included hysterectomy at 40 years of age, with no vaginal bleeding since the procedure.
One year earlier, routine laboratory testing had revealed mild thrombocytopenia and anemia. A bone marrow biopsy performed at that time had revealed slightly hypercellular marrow with maturing trilineage hematopoiesis but with some erythroid abnormalities and occasional hyperchromatic megakaryocytes; cytogenetic analysis had shown a loss of chromosomes 3 and 5 and a gain of chromosome 8 in 65% of the cells. Thereafter, blood counts monitored every 4 months, including 4 months before this presentation, had remained stable; laboratory test results are shown in Table 1.
Medications included amlodipine, atorvastatin, and hydrochlorothiazide. There were no known drug allergies. The patient drank alcohol occasionally and did not use illicit drugs. She had smoked tobacco for 50 years but had quit 5 years before this presentation. She was widowed and lived alone in New England; her work involved cleaning a church several days a week. Her sister had had breast cancer at 30 years of age, and a brother had had testicular cancer at a young age and liver cancer at 55 years of age.
On examination, the temperature was 36.8[degrees]C, the blood pressure 150/65 mm Hg, the pulse 72 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while oxygen was administered through a nasal cannula at a rate of 2 liters per minute. The patient was alert and oriented, and she did not appear ill. There were no petechiae. There was no bleeding at the site of tunneled catheter placement in the right internal jugular vein. The first and second heart sounds were normal; a grade 2/6 systolic murmur was heard at the left lower sternal border. The remainder of the physical examination was normal.
Examination of a peripheral-blood smear revealed schistocytes, anisocytosis, and a low platelet count, with large platelets present; the white cells appeared normal, and there were no blasts (Figure 2). The results of serum protein electrophoresis were normal. The levels of serum free kappa and lambda light chains were increased, with a normal ratio. Screening for human immunodeficiency virus infection was negative. Urinalysis showed 2+ urobilinogen, without bilirubin, blood, glucose, ketones, protein, or nitrates; the specific gravity and pH were normal. Consultation was obtained from the gynecology service regarding the bilateral pelvic masses noted on CT of the abdomen and pelvis. Blood levels of CA 125, CA 19-9, and carcinoembryonic antigen were normal, and follow-up in the gynecology clinic was recommended for further evaluation after discharge. Other laboratory test results are shown in Table 1.	
Figure 2 
A diagnostic test was performed, and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 80-year-old woman was admitted to this hospital because of pancytopenia and the identification of schistocytes on a peripheral-blood smear.
Six weeks before admission to this hospital, nausea, vomiting, and diarrhea developed, along with chills and subjective fever. The symptoms resolved after 4 days without specific intervention, but then intermittent dysphagia with solid foods and early satiety developed. During the next 4 weeks, the patient had gradually progressive fatigue and light-headedness. The fatigue progressed to the point that she could no longer stay at work for more than a few hours; she presented to another hospital for evaluation.
At the other hospital, the patient reported that she had ongoing fatigue and had lost 6 kg of weight over a 5-week period. On examination, the temperature was 38.9[degrees]C, the weight 55.5 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.9. Laboratory studies revealed pancytopenia, and examination of a peripheral-blood smear revealed schistocytes. Blood levels of glucose and electrolytes were normal, as were the results of kidney-function and liver-function tests; other laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
Dr. Ranjodh S. Dhami: A chest radiograph was normal. Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed a small hiatal hernia, multiple simple cysts in the right kidney, and indeterminate bilateral pelvic masses measuring 4.8 cm in diameter on the right side and 6.3 cm in diameter on the left side (Figure 1).	
Figure 1 
Dr. Pappas: Intravenous fluids were administered, and the patient was admitted to the other hospital. On hospital day 2, the hemoglobin level decreased to 6.6 g per deciliter, and two units of packed red cells were transfused. Esophagogastroduodenoscopy revealed diffuse esophageal inflammation with white exudates throughout the esophagus; examination of brushings revealed yeast consistent with candida, and treatment with fluconazole was initiated.
During the next 3 hospital days, the patient continued to feel unwell, with persistent fever and limited oral intake due to odynophagia, and the administration of intravenous fluids was continued. Blood and urine cultures showed no growth. On hospital day 5, empirical therapy with doxycycline was started because of concerns about a possible tickborne illness.
On hospital day 6, the oxygen saturation decreased to 89% while the patient was breathing ambient air and then increased to 94% when oxygen was delivered through a nasal cannula at a rate of 3 liters per minute. CT of the chest, performed after the administration of intravenous contrast material, revealed ground-glass opacities and interlobular septal thickening, findings consistent with pulmonary edema, along with bilateral pleural effusions of a small to moderate size. The administration of intravenous fluids was stopped, and one dose of intravenous furosemide was provided.
On hospital day 7, fever resolved but pancytopenia persisted. Examination of a peripheral-blood smear revealed a moderate amount of schistocytes, severe anisocytosis, large platelets, and an increased amount of bands without blasts. Direct and indirect Coombs' tests were negative, as were nucleic acid tests for babesiosis and anaplasmosis. Blood levels of electrolytes, glucose, cobalamin, folate, homocysteine, and anticardiolipin IgG and IgM were normal, as were the results of kidney-function and liver-function tests. The results of serologic tests for Epstein-Barr virus were consistent with previous infection. Flow cytometry of the peripheral blood showed phenotypically normal myeloid cells; there was an increased amount of atypical CD34+ myeloblasts, which accounted for less than 1% of leukocytes and were of unclear clinical significance.
A tunneled catheter was placed in the right internal jugular vein, and plasma exchange was initiated for the treatment of possible thrombotic thrombocytopenic purpura (TTP). Total parenteral nutrition was also initiated, because oral intake was still limited by odynophagia.
On hospital day 8, oral intake of soft foods and liquids increased. A transthoracic echocardiogram showed normal left ventricular size and function, as well as a mildly thickened aortic valve with no stenosis or regurgitation; there was trace mitral and tricuspid regurgitation. On hospital day 9, the patient underwent additional plasma exchange and was transferred to this hospital for further care.
On evaluation in this hospital, the patient reported that her energy level had increased. She recalled that she had felt mildly confused at the other hospital, but the confusion had since resolved. She had had no gum bleeding or blood in the stool or urine. Other medical history included hypertension and dyslipidemia. Surgical history included hysterectomy at 40 years of age, with no vaginal bleeding since the procedure.
One year earlier, routine laboratory testing had revealed mild thrombocytopenia and anemia. A bone marrow biopsy performed at that time had revealed slightly hypercellular marrow with maturing trilineage hematopoiesis but with some erythroid abnormalities and occasional hyperchromatic megakaryocytes; cytogenetic analysis had shown a loss of chromosomes 3 and 5 and a gain of chromosome 8 in 65% of the cells. Thereafter, blood counts monitored every 4 months, including 4 months before this presentation, had remained stable; laboratory test results are shown in Table 1.
Medications included amlodipine, atorvastatin, and hydrochlorothiazide. There were no known drug allergies. The patient drank alcohol occasionally and did not use illicit drugs. She had smoked tobacco for 50 years but had quit 5 years before this presentation. She was widowed and lived alone in New England; her work involved cleaning a church several days a week. Her sister had had breast cancer at 30 years of age, and a brother had had testicular cancer at a young age and liver cancer at 55 years of age.
On examination, the temperature was 36.8[degrees]C, the blood pressure 150/65 mm Hg, the pulse 72 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while oxygen was administered through a nasal cannula at a rate of 2 liters per minute. The patient was alert and oriented, and she did not appear ill. There were no petechiae. There was no bleeding at the site of tunneled catheter placement in the right internal jugular vein. The first and second heart sounds were normal; a grade 2/6 systolic murmur was heard at the left lower sternal border. The remainder of the physical examination was normal.
Examination of a peripheral-blood smear revealed schistocytes, anisocytosis, and a low platelet count, with large platelets present; the white cells appeared normal, and there were no blasts (Figure 2). The results of serum protein electrophoresis were normal. The levels of serum free kappa and lambda light chains were increased, with a normal ratio. Screening for human immunodeficiency virus infection was negative. Urinalysis showed 2+ urobilinogen, without bilirubin, blood, glucose, ketones, protein, or nitrates; the specific gravity and pH were normal. Consultation was obtained from the gynecology service regarding the bilateral pelvic masses noted on CT of the abdomen and pelvis. Blood levels of CA 125, CA 19-9, and carcinoembryonic antigen were normal, and follow-up in the gynecology clinic was recommended for further evaluation after discharge. Other laboratory test results are shown in Table 1.	
Figure 2 
A diagnostic test was performed, and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is an 80-year-old woman presenting with pancytopenia and schistocytes on a peripheral-blood smear. She has a history of nausea, vomiting, diarrhea, chills, fever, dysphagia, early satiety, fatigue, light-headedness, and weight loss. She also has a history of hypertension and dyslipidemia. Her symptoms and the presence of schistocytes suggest a microangiopathic hemolytic anemia, such as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS). However, her kidney function is normal, which makes HUS less likely. The presence of fever, neurological symptoms (confusion), and the laboratory findings (pancytopenia and schistocytes) meet the classic pentad of TTP symptoms. Furthermore, her condition improved with plasma exchange, a standard treatment for TTP. \n\nDiagnosis: Thrombotic Thrombocytopenic Purpura (TTP)""
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        ""content"": ""The patient is an 80-year-old woman presenting with pancytopenia and schistocytes on a peripheral-blood smear. She has a history of nausea, vomiting, diarrhea, chills, fever, dysphagia, early satiety, fatigue, light-headedness, and weight loss. The differential diagnosis for this patient includes thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), disseminated intravascular coagulation (DIC), paroxysmal nocturnal hemoglobinuria (PNH), and myelodysplastic syndrome (MDS). \n\nThe presence of schistocytes on a peripheral-blood smear suggests a microangiopathic hemolytic anemia, which is seen in conditions like TTP, HUS, and DIC. However, the patient does not have renal impairment or a diarrheal prodrome, making HUS less likely. She also does not have a known precipitating cause for DIC such as sepsis, malignancy, or trauma, making DIC less likely. \n\nTTP is a possibility given the presence of schistocytes and the patient's neurological symptoms (confusion), but she does not have the full pentad of symptoms (thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, renal impairment, and fever). \n\nPNH could also cause pancytopenia and hemolytic anemia, but it is less likely given the absence of dark urine and the presence of schistocytes, which are not typically seen in PNH. \n\nThe patient's history of mild thrombocytopenia and anemia, along with the findings on a previous bone marrow biopsy (slightly hypercellular marrow with maturing trilineage hematopoiesis but with some erythroid abnormalities and occasional hyperchromatic megakaryocytes; cytogenetic analysis showing a loss of chromosomes 3 and 5 and a gain of chromosome 8 in 65% of the cells) are suggestive of MDS. The presence of pancytopenia and schistocytes could be explained by progression of MDS to a more severe form or transformation to acute myeloid leukemia.\n\nDiagnosis:\nMyelodysplastic syndrome (MDS) is the most likely diagnosis.""
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}",Myelodysplastic syndrome (MDS) is the most likely diagnosis,Y
10.1056/NEJMcpc2201230,Case 10-2022: A 78-Year-Old Man with Marked Ventricular Wall Thickening,,Fabry's disease.,Fabry's disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
 A 78-year-old man was evaluated in the cardiology clinic of this hospital because of biventricular myocardial wall thickening, progressive mitral regurgitation, and ventricular arrhythmias.
The patient had been a distinguished multisport athlete in high school and college. However, in his 20s, he found that he was unable to perform competitively, and he noticed that he did not sweat as much as his teammates. After an episode of sports-related exertional dizziness, he was evaluated by a physician, and a diagnosis of hypertrophic cardiomyopathy was considered.
Twenty-five years before the current evaluation, a transthoracic echocardiogram (TTE) reportedly showed a symmetric left ventricular wall thickness of 19 mm (reference value, <=11), a left ventricular ejection fraction of 74% (reference range, 50 to 75), mitral valve thickening, and trace mitral regurgitation, with no left ventricular outflow gradient. An electrocardiogram showed sinus rhythm, incomplete right bundle-branch block, precordial J-point elevation, and QRS voltage that met the electrocardiographic criteria for left ventricular hypertrophy (Figure 1A). The patient's blood pressure was 160/90 mm Hg, and he started treatment with metoprolol succinate and then also with amlodipine for elevated blood pressure.	
Figure 1 
During the next 10 years, the patient had intermittent chest discomfort, exertional dyspnea, and leg edema. The chest discomfort and exertional dyspnea were most likely to occur when he was walking or after he had eaten a meal. He was evaluated by three cardiologists; treatment with metoprolol succinate and amlodipine was continued, treatment with enalapril was started, and triamterene-hydrochlorothiazide was administered as needed for leg edema.
A repeat TTE reportedly showed a symmetric left ventricular wall thickness of 20 mm, a normal left ventricular ejection fraction, right ventricular wall thickening, left atrial enlargement, mitral valve thickening, mild-to-moderate mitral regurgitation, aortic valve thickening, and mild ascending aortic dilatation (39 mm), with no evidence of left ventricular outflow tract obstruction and no evidence of systolic anterior motion of the mitral valve. An exercise stress test followed by imaging performed with the use of sestamibi (known as a sestamibi stress test) revealed left ventricular wall thickening, with no perfusion defects. Coronary angiography revealed evidence of chronic total occlusion of the distal left anterior descending artery, with collateral flow from both the left and right coronary arteries. Left ventriculography revealed hyperdynamic left ventricular function and 2+ mitral regurgitation (see Video 1, available with the full text of this article at NEJM.org). The left ventricular end-diastolic pressure was 28 mm Hg (reference range, 5 to 10), with no left ventricular intracavitary gradient, including during ventricular ectopic beats and during the Valsalva maneuver, and with no evidence of left ventricular outflow tract obstruction. The blood pressure remained well controlled while the patient was taking metoprolol, amlodipine, and enalapril.
Nine years before the current evaluation, the patient had complete heart block with symptomatic bradycardia (Figure 1B), with associated nausea, dizziness, and chest discomfort. A temporary transvenous pacing wire was placed; the results of coronary angiography performed at that time were unchanged from the previous study. The creatinine level was 1.2 mg per deciliter (106 [mu]mol per liter; reference range, 0.6 to 1.5 mg per deciliter [53 to 133 [mu]mol per liter]); the blood levels of electrolytes and thyrotropin were normal, as were the results of serum protein electrophoresis. A dual-chamber implantable cardioverter-defibrillator (ICD) was placed. Four months later, atrial fibrillation developed. Cardioversion was performed with guidance by transesophageal echocardiography, resulting in sinus rhythm. However, atrial fibrillation recurred after 3 days. Treatment with amiodarone and warfarin was begun.
During the next 5 years, recurrent nonsustained ventricular tachyarrhythmias were detected on ICD interrogation. A repeat TTE showed a left ventricular wall thickness of 23 mm and moderate-to-severe mitral regurgitation.
Four years before the current evaluation, during a holiday trip, the patient was hospitalized in another state because of pulmonary edema that developed after he had consumed food that was high in sodium. He was treated with intravenous furosemide and discharged with a prescription for oral furosemide. Findings on TTE were reportedly similar to those observed previously. Treatment with amlodipine was stopped because of lightheadedness.
At follow-up appointments during the next 4 years, the patient reported fatigue and exertional dyspnea that occurred after he had climbed one flight of stairs or when he was walking on an incline. In addition, he had nocturia once per night, slept on two pillows, and had intermittent wheezing, including episodes that awakened him from sleep. Treatment with oral furosemide (administered twice daily) was continued. Recurrent nonsustained ventricular tachyarrhythmias were detected on ICD interrogation. Approximately 3.5 years before the current evaluation, the patient sustained a fall that was unrelated to his cardiac condition. At that time, computed tomography of the head, performed without the administration of intravenous contrast material, did not reveal any evidence of hemorrhage or stroke but showed periventricular and deep white-matter hypodensities. Results of pulmonary-function testing were normal.
The patient presented for the current evaluation at the request of his two teenage grandsons, who wanted to know about any familial cardiac risk factors that could influence their participation in sports. A review of systems was notable for intermittent palpitations, chronic dry eyes, reduced hearing, tinnitus in both ears (greater in the right ear than in the left ear), restless legs, and constipation. The patient reported no headache, paresthesia, stroke symptoms, diarrhea, skin changes, or intolerance to heat or cold. His medical history included cardiomyopathy, coronary artery disease, atrioventricular block and atrial fibrillation, dyslipidemia, hypertension, progressive renal insufficiency, cataracts, and prostatic hypertrophy with carcinoma in situ. Medications included furosemide, warfarin, amiodarone, aspirin, atorvastatin, metoprolol, enalapril, and tamsulosin, as well as inhaled fluticasone. Amiodarone had caused thyroiditis, which had been treated with a course of prednisone; there were no other known adverse reactions to medication.
The patient was a retired executive and lived with his spouse in Massachusetts. His family history was notable for brain cancer in his father, obstructive lung disease and lung cancer in his mother, and lung cancer in his sister, who had died from the disease. There was also a history of hypertrophic cardiomyopathy in his sister and in a niece. His family was of Mediterranean origin; information about other relatives was limited. His son and grandsons were healthy, and his son had reportedly had normal results on an electrocardiogram and echocardiograms. The patient did not drink alcohol and had never used tobacco.
On examination, the heart rate was 79 beats per minute and the blood pressure 106/60 mm Hg. The weight was 89 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 26.6. There was a left ventricular heave. Auscultation revealed splitting of the S2 heart sound, a grade 3/6 systolic murmur that could be heard throughout the precordium and did not change during the Valsalva maneuver, and a grade 2/6 holosystolic murmur at the apex that radiated to the axilla; there was no S3 heart sound. There was trace leg edema and mild chronic venous stasis. The rest of the examination was normal.
Laboratory test results were notable for a creatinine level of 1.5 mg per deciliter (133 [mu]mol per liter), a urea nitrogen level of 39 mg per deciliter (13.9 mmol per liter; reference range, 8 to 25 mg per deciliter [2.9 to 8.9 mmol per liter]), an international normalized ratio of 2.1 (reference range, 0.9 to 1.1), and an N-terminal pro-B-type natriuretic peptide level of 2523 pg per milliliter (reference range, 0 to 1800), as well as 1+ protein on urinalysis. The blood levels of iron, glycated hemoglobin, thyrotropin, and free thyroxine were normal, and a test for antinuclear antibodies was negative. An electrocardiogram showed atrial fibrillation with ventricular pacing.
A TTE was obtained, and additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
 A 78-year-old man was evaluated in the cardiology clinic of this hospital because of biventricular myocardial wall thickening, progressive mitral regurgitation, and ventricular arrhythmias.
The patient had been a distinguished multisport athlete in high school and college. However, in his 20s, he found that he was unable to perform competitively, and he noticed that he did not sweat as much as his teammates. After an episode of sports-related exertional dizziness, he was evaluated by a physician, and a diagnosis of hypertrophic cardiomyopathy was considered.
Twenty-five years before the current evaluation, a transthoracic echocardiogram (TTE) reportedly showed a symmetric left ventricular wall thickness of 19 mm (reference value, <=11), a left ventricular ejection fraction of 74% (reference range, 50 to 75), mitral valve thickening, and trace mitral regurgitation, with no left ventricular outflow gradient. An electrocardiogram showed sinus rhythm, incomplete right bundle-branch block, precordial J-point elevation, and QRS voltage that met the electrocardiographic criteria for left ventricular hypertrophy (Figure 1A). The patient's blood pressure was 160/90 mm Hg, and he started treatment with metoprolol succinate and then also with amlodipine for elevated blood pressure.	
Figure 1 
During the next 10 years, the patient had intermittent chest discomfort, exertional dyspnea, and leg edema. The chest discomfort and exertional dyspnea were most likely to occur when he was walking or after he had eaten a meal. He was evaluated by three cardiologists; treatment with metoprolol succinate and amlodipine was continued, treatment with enalapril was started, and triamterene-hydrochlorothiazide was administered as needed for leg edema.
A repeat TTE reportedly showed a symmetric left ventricular wall thickness of 20 mm, a normal left ventricular ejection fraction, right ventricular wall thickening, left atrial enlargement, mitral valve thickening, mild-to-moderate mitral regurgitation, aortic valve thickening, and mild ascending aortic dilatation (39 mm), with no evidence of left ventricular outflow tract obstruction and no evidence of systolic anterior motion of the mitral valve. An exercise stress test followed by imaging performed with the use of sestamibi (known as a sestamibi stress test) revealed left ventricular wall thickening, with no perfusion defects. Coronary angiography revealed evidence of chronic total occlusion of the distal left anterior descending artery, with collateral flow from both the left and right coronary arteries. Left ventriculography revealed hyperdynamic left ventricular function and 2+ mitral regurgitation (see Video 1, available with the full text of this article at NEJM.org). The left ventricular end-diastolic pressure was 28 mm Hg (reference range, 5 to 10), with no left ventricular intracavitary gradient, including during ventricular ectopic beats and during the Valsalva maneuver, and with no evidence of left ventricular outflow tract obstruction. The blood pressure remained well controlled while the patient was taking metoprolol, amlodipine, and enalapril.
Nine years before the current evaluation, the patient had complete heart block with symptomatic bradycardia (Figure 1B), with associated nausea, dizziness, and chest discomfort. A temporary transvenous pacing wire was placed; the results of coronary angiography performed at that time were unchanged from the previous study. The creatinine level was 1.2 mg per deciliter (106 [mu]mol per liter; reference range, 0.6 to 1.5 mg per deciliter [53 to 133 [mu]mol per liter]); the blood levels of electrolytes and thyrotropin were normal, as were the results of serum protein electrophoresis. A dual-chamber implantable cardioverter-defibrillator (ICD) was placed. Four months later, atrial fibrillation developed. Cardioversion was performed with guidance by transesophageal echocardiography, resulting in sinus rhythm. However, atrial fibrillation recurred after 3 days. Treatment with amiodarone and warfarin was begun.
During the next 5 years, recurrent nonsustained ventricular tachyarrhythmias were detected on ICD interrogation. A repeat TTE showed a left ventricular wall thickness of 23 mm and moderate-to-severe mitral regurgitation.
Four years before the current evaluation, during a holiday trip, the patient was hospitalized in another state because of pulmonary edema that developed after he had consumed food that was high in sodium. He was treated with intravenous furosemide and discharged with a prescription for oral furosemide. Findings on TTE were reportedly similar to those observed previously. Treatment with amlodipine was stopped because of lightheadedness.
At follow-up appointments during the next 4 years, the patient reported fatigue and exertional dyspnea that occurred after he had climbed one flight of stairs or when he was walking on an incline. In addition, he had nocturia once per night, slept on two pillows, and had intermittent wheezing, including episodes that awakened him from sleep. Treatment with oral furosemide (administered twice daily) was continued. Recurrent nonsustained ventricular tachyarrhythmias were detected on ICD interrogation. Approximately 3.5 years before the current evaluation, the patient sustained a fall that was unrelated to his cardiac condition. At that time, computed tomography of the head, performed without the administration of intravenous contrast material, did not reveal any evidence of hemorrhage or stroke but showed periventricular and deep white-matter hypodensities. Results of pulmonary-function testing were normal.
The patient presented for the current evaluation at the request of his two teenage grandsons, who wanted to know about any familial cardiac risk factors that could influence their participation in sports. A review of systems was notable for intermittent palpitations, chronic dry eyes, reduced hearing, tinnitus in both ears (greater in the right ear than in the left ear), restless legs, and constipation. The patient reported no headache, paresthesia, stroke symptoms, diarrhea, skin changes, or intolerance to heat or cold. His medical history included cardiomyopathy, coronary artery disease, atrioventricular block and atrial fibrillation, dyslipidemia, hypertension, progressive renal insufficiency, cataracts, and prostatic hypertrophy with carcinoma in situ. Medications included furosemide, warfarin, amiodarone, aspirin, atorvastatin, metoprolol, enalapril, and tamsulosin, as well as inhaled fluticasone. Amiodarone had caused thyroiditis, which had been treated with a course of prednisone; there were no other known adverse reactions to medication.
The patient was a retired executive and lived with his spouse in Massachusetts. His family history was notable for brain cancer in his father, obstructive lung disease and lung cancer in his mother, and lung cancer in his sister, who had died from the disease. There was also a history of hypertrophic cardiomyopathy in his sister and in a niece. His family was of Mediterranean origin; information about other relatives was limited. His son and grandsons were healthy, and his son had reportedly had normal results on an electrocardiogram and echocardiograms. The patient did not drink alcohol and had never used tobacco.
On examination, the heart rate was 79 beats per minute and the blood pressure 106/60 mm Hg. The weight was 89 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 26.6. There was a left ventricular heave. Auscultation revealed splitting of the S2 heart sound, a grade 3/6 systolic murmur that could be heard throughout the precordium and did not change during the Valsalva maneuver, and a grade 2/6 holosystolic murmur at the apex that radiated to the axilla; there was no S3 heart sound. There was trace leg edema and mild chronic venous stasis. The rest of the examination was normal.
Laboratory test results were notable for a creatinine level of 1.5 mg per deciliter (133 [mu]mol per liter), a urea nitrogen level of 39 mg per deciliter (13.9 mmol per liter; reference range, 8 to 25 mg per deciliter [2.9 to 8.9 mmol per liter]), an international normalized ratio of 2.1 (reference range, 0.9 to 1.1), and an N-terminal pro-B-type natriuretic peptide level of 2523 pg per milliliter (reference range, 0 to 1800), as well as 1+ protein on urinalysis. The blood levels of iron, glycated hemoglobin, thyrotropin, and free thyroxine were normal, and a test for antinuclear antibodies was negative. An electrocardiogram showed atrial fibrillation with ventricular pacing.
A TTE was obtained, and additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's history of hypertrophic cardiomyopathy, progressive renal insufficiency, and family history of cardiomyopathy suggest a systemic disease. The patient's symptoms of dry eyes, reduced hearing, and tinnitus suggest involvement of other organ systems. The patient's history of not sweating as much as his teammates and intolerance to heat suggest autonomic dysfunction. These findings are consistent with a diagnosis of systemic amyloidosis, which can cause restrictive cardiomyopathy and renal disease. The patient's family history of cardiomyopathy suggests a hereditary form of the disease.\n\nDiagnosis: Hereditary systemic amyloidosis.""
      },
      ""finish_reason"": ""stop""
    }
  ],
  ""usage"": {
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}","{
  ""id"": ""chatcmpl-7htW76jAwBUfFdn2F5qMLRvR5qtCW"",
  ""object"": ""chat.completion"",
  ""created"": 1690695867,
  ""model"": ""gpt-4-0613"",
  ""choices"": [
    {
      ""index"": 0,
      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient's history of biventricular myocardial wall thickening, progressive mitral regurgitation, and ventricular arrhythmias, along with symptoms of exertional dyspnea, leg edema, and intermittent chest discomfort, suggest a cardiac condition. The patient's history of hypertrophic cardiomyopathy, a condition characterized by thickening of the heart muscle, is also significant. However, the patient's additional symptoms of dry eyes, reduced hearing, tinnitus, and restless legs, along with the family history of hypertrophic cardiomyopathy, suggest a systemic condition. The patient's history of progressive renal insufficiency and protein in the urine also suggest a systemic condition affecting multiple organs. The combination of cardiac symptoms, systemic symptoms, and family history suggest a hereditary systemic condition. The most likely diagnosis is Fabry disease, a genetic disorder that can cause a variety of symptoms, including cardiac symptoms, renal disease, and neurological symptoms.\n\nDiagnosis: Fabry disease.""
      },
      ""finish_reason"": ""stop""
    }
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  ""usage"": {
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}",Fabry diseas,Y,"{
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  ""created"": 1690695904,
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    {
      ""index"": 0,
      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient is a 78-year-old man with a history of hypertrophic cardiomyopathy, coronary artery disease, atrioventricular block and atrial fibrillation, dyslipidemia, hypertension, and progressive renal insufficiency. He presents with biventricular myocardial wall thickening, progressive mitral regurgitation, and ventricular arrhythmias. The differential diagnosis for this patient includes hypertrophic cardiomyopathy, amyloidosis, and Fabry disease. The patient's history of hypertrophic cardiomyopathy and the echocardiogram findings of symmetric left ventricular wall thickness support this diagnosis. However, the patient's age and the presence of biventricular wall thickening and progressive mitral regurgitation suggest a systemic disease such as amyloidosis. Fabry disease could also present with hypertrophic cardiomyopathy, but it is less likely given the patient's age and lack of other typical symptoms such as angiokeratomas and neuropathic pain. The patient's history of dry eyes, reduced hearing, tinnitus, and restless legs could be consistent with amyloidosis, which can affect multiple organ systems. The presence of protein in the urine also supports a diagnosis of amyloidosis, which can cause renal involvement. \n\nDiagnosis: Amyloidosis.""
      },
      ""finish_reason"": ""stop""
    }
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  ""usage"": {
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}",Amyloidosis,N
10.1056/NEJMcpc2115846,"Case 9-2022: A 56-Year-Old Woman 
with Fever, Myalgias, Diarrhea, and Cough","Hemoglobin (g/dl)   13.4 10.5 11.5
Hematocrit (%)   40.1 31.5 35.8
Mean corpuscular volume (fl)   95.2 94.9 97.0
Platelet count (per μl)   106,000 84,000 262,000
White-cell count (per μl)   4490 3500 6250
Differential count (per μl)
Neutrophils   2990 2290 4430
Lymphocytes   950 620 1140
Monocytes   470 500 630
Eosinophils   40 — —
Basophils  00 40 60 60
Sodium (mmol/liter) 134–140 138 137 137
Potassium (mmol/liter) 3.6–5.0 4.4 3.9 4.0
Chloride (mmol/liter)   97 103 100
Carbon dioxide (mmol/liter) 21–31 26 23 23
Anion gap (mmol/liter)   25 15 14
Glucose (mg/dl)   104 138 113
Calcium (mg/dl) 8.4–10.2 8.7 8.1 9.2
Phosphorus (mg/dl)   1.0 2.7 —
Urea nitrogen (mg/dl) 7–18 25 15 14
Creatinine (mg/dl) 0.42–1.09 0.86 0.85 1.01
Lactic acid (mmol/liter)   — — 0.7
Alanine aminotransferase (U/liter)   50 111 326
Aspartate aminotransferase (U/liter) 10–42 51 162 326
Alkaline phosphatase (U/liter) 32–92 109 98 137
Total bilirubin (mg/dl) 0.2–1.0 0.5 0.3 0.5
Albumin (g/dl) 3.8–5.0 3.6 3.1 3.5
Lactate dehydrogenase (U/liter) 11 10 276 309 —
High-sensitivity troponin T (ng/liter) 0–9 <6 — —
Creatine kinase (U/liter)   31 — —
Ferritin (μg/liter) 1 00 487 572 1358
d-dimer (ng/ml)   1306 1406 2222
C-reactive protein (mg/liter)   36.6 69.2 169.3
Erythrocyte sedimentation rate (mm/hr)  0 18 21 62",Anaplasmosis.,Anaplasmosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 56-year-old woman was admitted to this hospital in the spring of 2020, during the initial surge of the coronavirus disease 2019 (Covid-19) pandemic in Boston, because of fever, myalgias, diarrhea, and a dry cough.
Six weeks before this admission, the patient had contact with a person with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. At that time, she did not have any symptoms compatible with Covid-19 and was not tested for SARS-CoV-2.
Four weeks before this admission, in accordance with statewide recommendations from the Department of Public Health, the patient began isolating at home with her teenage son, working from home, and having groceries delivered. Two weeks before this admission, she and her son left home for a few hours to eat outdoors and spend time in a wooded area; they otherwise remained at home.
Six days before this admission, fever, chills, and myalgias developed. The next day, watery diarrhea occurred. The patient's temperature measured at home was 38.3[degrees]C; fever persisted despite the intermittent administration of acetaminophen. Three days before this admission, a frontal headache developed, along with a dry cough that was associated with a self-limited episode of chest pain. The patient's son had had no symptoms, except for a self-limited episode of diarrhea 2 weeks before the patient's symptoms developed. On the day of admission, the patient continued to have fever, so she presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported ongoing myalgias, headache, and cough. There was no nausea, vomiting, rash, shortness of breath, or anosmia. She had no notable medical history and took no medications. She was allergic to amoxicillin, with an unknown reaction. She did not smoke tobacco and drank alcohol rarely; she did not use illicit drugs. The patient lived in an urban area of New England and had traveled to Canada 6 months before this admission. She had a pet cat; there was no other animal contact.
On examination, the patient appeared anxious, but breathing was unlabored. The temperature was 38.9[degrees]C, the blood pressure 121/64 mm Hg, the heart rate 124 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 95% at rest and 98% during ambulation, both while she was breathing ambient air. The patient was alert and oriented to time, place, and person. There were no focal neurologic deficits. There was no meningism. The mucous membranes were dry. The first and second heart sounds were normal, without additional sounds or murmurs. There were vesicular breath sounds. The abdomen was soft and nontender, without hepatosplenomegaly. There was no rash. Laboratory test results are shown in Table 1.	
Table 1 
Dr. Patrick P. Bourgouin: Chest radiography revealed low lung volumes, without evidence of pneumonia or pulmonary edema.
Dr. Castle: SARS-CoV-2 nucleic acid testing of a nasopharyngeal specimen was negative, as was testing for adenovirus, human metapneumovirus, influenza virus types A and B, parainfluenza virus types 1 through 4, respiratory syncytial virus, human rhinovirus and enterovirus, Bordetella pertussis, B. parapertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Blood cultures were negative. Urinalysis was negative for leukocyte esterase and nitrites. The procalcitonin level was 0.36 ng per milliliter (reference range, 0.00 to 0.08). Intravenous fluids and acetaminophen were administered, and the heart rate decreased to 93 beats per minute. The patient was admitted to this hospital because of concerns that she had Covid-19.
On the second hospital day, the patient had ongoing diarrhea, headache, and cough, along with fatigue. The temperature was 40.2[degrees]C, the blood pressure 115/64 mm Hg, the heart rate 89 beats per minute, and the oxygen saturation 96% while she was breathing ambient air. The administration of intravenous fluids was continued. SARS-CoV-2 nucleic acid testing of a second nasopharyngeal specimen was negative. Laboratory test results are shown in Table 1. On the third hospital day, the temperature was 38.7[degrees]C.
Dr. Bourgouin: Computed tomography (CT) of the chest, performed without the administration of intravenous contrast material, revealed interlobular septal thickening, mild ground-glass opacities at the lung bases, and small bilateral pleural effusions (Figure 1).	
Figure 1
Dr. Castle: During the next 3 days, the patient had ongoing myalgias, headache, and cough. Fever persisted, and the oxygen saturation remained normal. Urine antigen testing for legionella and Streptococcus pneumoniae antigens was negative, as was screening for human immunodeficiency virus (HIV) types 1 and 2 and nucleic acid testing of a blood specimen for cytomegalovirus and Epstein-Barr virus. Blood cultures remained negative.
On the seventh hospital day, diarrhea resolved, but fever, myalgias, headache, and cough persisted. The physical examination was unchanged, with a normal oxygen saturation during ambulation.
Dr. Bourgouin: Chest radiography revealed no evidence of pneumonia.
Dr. Castle: The procalcitonin level was 0.57 ng per milliliter; other laboratory test results are shown in Table 1. Levofloxacin was administered. On the eighth hospital day, fever resolved but headache and fatigue persisted.
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 56-year-old woman was admitted to this hospital in the spring of 2020, during the initial surge of the coronavirus disease 2019 (Covid-19) pandemic in Boston, because of fever, myalgias, diarrhea, and a dry cough.
Six weeks before this admission, the patient had contact with a person with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. At that time, she did not have any symptoms compatible with Covid-19 and was not tested for SARS-CoV-2.
Four weeks before this admission, in accordance with statewide recommendations from the Department of Public Health, the patient began isolating at home with her teenage son, working from home, and having groceries delivered. Two weeks before this admission, she and her son left home for a few hours to eat outdoors and spend time in a wooded area; they otherwise remained at home.
Six days before this admission, fever, chills, and myalgias developed. The next day, watery diarrhea occurred. The patient's temperature measured at home was 38.3[degrees]C; fever persisted despite the intermittent administration of acetaminophen. Three days before this admission, a frontal headache developed, along with a dry cough that was associated with a self-limited episode of chest pain. The patient's son had had no symptoms, except for a self-limited episode of diarrhea 2 weeks before the patient's symptoms developed. On the day of admission, the patient continued to have fever, so she presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported ongoing myalgias, headache, and cough. There was no nausea, vomiting, rash, shortness of breath, or anosmia. She had no notable medical history and took no medications. She was allergic to amoxicillin, with an unknown reaction. She did not smoke tobacco and drank alcohol rarely; she did not use illicit drugs. The patient lived in an urban area of New England and had traveled to Canada 6 months before this admission. She had a pet cat; there was no other animal contact.
On examination, the patient appeared anxious, but breathing was unlabored. The temperature was 38.9[degrees]C, the blood pressure 121/64 mm Hg, the heart rate 124 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 95% at rest and 98% during ambulation, both while she was breathing ambient air. The patient was alert and oriented to time, place, and person. There were no focal neurologic deficits. There was no meningism. The mucous membranes were dry. The first and second heart sounds were normal, without additional sounds or murmurs. There were vesicular breath sounds. The abdomen was soft and nontender, without hepatosplenomegaly. There was no rash. Laboratory test results are shown in Table 1.	
Table 1 
Dr. Patrick P. Bourgouin: Chest radiography revealed low lung volumes, without evidence of pneumonia or pulmonary edema.
Dr. Castle: SARS-CoV-2 nucleic acid testing of a nasopharyngeal specimen was negative, as was testing for adenovirus, human metapneumovirus, influenza virus types A and B, parainfluenza virus types 1 through 4, respiratory syncytial virus, human rhinovirus and enterovirus, Bordetella pertussis, B. parapertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Blood cultures were negative. Urinalysis was negative for leukocyte esterase and nitrites. The procalcitonin level was 0.36 ng per milliliter (reference range, 0.00 to 0.08). Intravenous fluids and acetaminophen were administered, and the heart rate decreased to 93 beats per minute. The patient was admitted to this hospital because of concerns that she had Covid-19.
On the second hospital day, the patient had ongoing diarrhea, headache, and cough, along with fatigue. The temperature was 40.2[degrees]C, the blood pressure 115/64 mm Hg, the heart rate 89 beats per minute, and the oxygen saturation 96% while she was breathing ambient air. The administration of intravenous fluids was continued. SARS-CoV-2 nucleic acid testing of a second nasopharyngeal specimen was negative. Laboratory test results are shown in Table 1. On the third hospital day, the temperature was 38.7[degrees]C.
Dr. Bourgouin: Computed tomography (CT) of the chest, performed without the administration of intravenous contrast material, revealed interlobular septal thickening, mild ground-glass opacities at the lung bases, and small bilateral pleural effusions (Figure 1).	
Figure 1
Dr. Castle: During the next 3 days, the patient had ongoing myalgias, headache, and cough. Fever persisted, and the oxygen saturation remained normal. Urine antigen testing for legionella and Streptococcus pneumoniae antigens was negative, as was screening for human immunodeficiency virus (HIV) types 1 and 2 and nucleic acid testing of a blood specimen for cytomegalovirus and Epstein-Barr virus. Blood cultures remained negative.
On the seventh hospital day, diarrhea resolved, but fever, myalgias, headache, and cough persisted. The physical examination was unchanged, with a normal oxygen saturation during ambulation.
Dr. Bourgouin: Chest radiography revealed no evidence of pneumonia.
Dr. Castle: The procalcitonin level was 0.57 ng per milliliter; other laboratory test results are shown in Table 1. Levofloxacin was administered. On the eighth hospital day, fever resolved but headache and fatigue persisted.
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with fever, myalgias, diarrhea, and a dry cough, which are symptoms consistent with COVID-19. However, she tested negative for SARS-CoV-2 twice. She also tested negative for other common respiratory pathogens. The patient had contact with a confirmed COVID-19 case six weeks prior to admission, but did not develop symptoms until six days before admission. Her chest CT showed interlobular septal thickening, mild ground-glass opacities at the lung bases, and small bilateral pleural effusions, which can be seen in COVID-19, but also in other conditions. Her symptoms persisted despite the absence of a confirmed infection. Given the negative tests for other pathogens, the patient's symptoms, and the imaging findings, the most likely diagnosis is COVID-19, despite the negative SARS-CoV-2 tests. False negatives can occur in SARS-CoV-2 testing.\n\nDiagnosis: COVID-19 (despite negative SARS-CoV-2 tests)""
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        ""content"": ""The patient presented with fever, myalgias, diarrhea, and a dry cough. She had contact with a person with confirmed SARS-CoV-2 infection six weeks prior to admission, but her SARS-CoV-2 nucleic acid testing was negative. She had ongoing symptoms including fever, myalgias, headache, and cough. Her chest CT revealed interlobular septal thickening, mild ground-glass opacities at the lung bases, and small bilateral pleural effusions. These findings are not typical for COVID-19, which usually presents with more extensive ground-glass opacities. Her symptoms, contact history, and the timing of her illness onset during the initial surge of the COVID-19 pandemic in Boston initially suggested COVID-19, but her negative SARS-CoV-2 tests and atypical imaging findings suggest another diagnosis. Given her symptoms and the imaging findings, a possible diagnosis is atypical pneumonia caused by a pathogen not covered by the respiratory panel, such as Legionella or Mycoplasma. However, her urine antigen tests for these pathogens were negative. Another possibility is a non-infectious cause of her symptoms, such as an autoimmune or inflammatory condition. However, her symptoms and imaging findings are not typical for these conditions. The final diagnosis is not clear based on the information provided.\n\nDiagnosis: Unclear, further investigation needed.""
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        ""content"": ""The patient is a 56-year-old woman presenting with fever, myalgias, diarrhea, and a dry cough. She had contact with a person with confirmed SARS-CoV-2 infection six weeks prior to admission, but did not show symptoms at that time. The differential diagnosis for this patient includes COVID-19, influenza, other respiratory viruses, bacterial pneumonia, and possibly a non-infectious cause such as a vasculitis or autoimmune disease. However, the patient's symptoms started six days prior to admission, which is within the typical incubation period for COVID-19. Furthermore, her symptoms of fever, myalgias, diarrhea, and dry cough are all common in COVID-19. However, the patient tested negative for SARS-CoV-2 twice, which makes COVID-19 less likely, although false negatives are possible. The patient also tested negative for other common respiratory viruses and bacteria. The patient's chest CT showed interlobular septal thickening, mild ground-glass opacities at the lung bases, and small bilateral pleural effusions, which can be seen in COVID-19, but also in other conditions such as heart failure, other viral pneumonias, and interstitial lung diseases. The patient's procalcitonin level was elevated, which is more commonly seen in bacterial infections, but can also be elevated in severe viral infections. Given the patient's history of contact with a confirmed COVID-19 case, her symptoms, and the imaging findings, COVID-19 is still a possibility despite the negative tests. However, given the negative tests and the elevated procalcitonin, a bacterial infection cannot be ruled out. \n\nDiagnosis: \nThe diagnosis is unclear based on the provided information. Further diagnostic testing is needed.""
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}",The diagnosis is unclear based on the provided information. Further diagnostic testing is needed,N
10.1056/NEJMcpc2027087,Case 8-2022: A 54-Year-Old Woman with Episodes of Swelling.,"Total complement (U/ml) 63–145 129 15 50 149
C3 (mg/dl) 86–184 159 90–180 152
C4 (mg/dl) 20–58     8
C2 (mg/dl) 1.58–3.92 2.45 1.58–3.92 1.6
C1 inhibitor level (mg/dl) 12.4–24.5 2.4 21–39 7
C1 inhibitor function† Present Present Present Present
C1q (mg/dl) 8–12 6.9 8–12 7",Hereditary angioedema with C1 inhibitor deficiency and chronic spontaneous urticaria,Hereditary angioedema with C1 inhibitor deficiency and chronic spontaneous urticaria,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 54-year-old woman with a history of episodic swelling of the arms, hands, and feet was evaluated in the emergency department of this hospital because of abdominal pain, nausea, and vomiting.
Twenty-three years before the current presentation, swelling of the left hand developed after the patient sustained a human bite. The swelling was associated with mild pruritus, erythema, and warmth. The swelling was well demarcated, involved only the left hand, and resolved after 3 days without specific treatment.
Twenty-two years before the current presentation, the patient had epigastric pain that radiated to her back, with associated nausea. Results of an upper gastrointestinal series, computed tomography (CT) of the abdomen, hepatobiliary scintigraphy, and esophagogastroduodenoscopy were reportedly normal. The abdominal pain resolved, but two similar self-limited episodes occurred during the next year. No cause for the abdominal pain was identified.
During the next 3 years, episodes of self-limited swelling occurred once per year; one episode involved the right foot, one the left hand, and one the right hand. There were no clear triggers for the episodes, although they tended to occur after exposure to cold or after minor trauma, such as scratching.
Eighteen years before the current presentation, episodes of swelling of the hands and feet began to occur on a monthly basis, and the patient was evaluated at another hospital after an episode of swelling of the left hand. A skin-biopsy specimen reportedly showed sparse superficial dermal perivascular and interstitial mixed inflammatory infiltrate and stromal edema. Treatment with prednisone was initiated. The swelling of the left hand resolved after 3 days, and the patient was referred to the allergy clinic of this hospital. Laboratory test results are shown in Table 1. A diagnosis of acquired C1 inhibitor deficiency was made on the basis of low levels of C1 esterase inhibitor, C4, and C1q. Results of serum protein electrophoresis were normal, and tests for antinuclear antibodies were negative. The patient was evaluated in the allergy clinic of a third hospital, and treatment with daily danazol was initiated. The episodes of swelling of the hands and feet resolved.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Ten years before the current presentation, episodes of swelling of the eyelids and upper lip occurred with associated pruritus. The episodes began with a sensation of facial flushing, pruritus of the scalp, and a raised pruritic rash on the face and chest; at times, these episodes were accompanied by shortness of breath, chest tightness, itchy throat, and red eyes. The patient was evaluated in the allergy clinic of the third hospital. Laboratory test results are shown in Table 1. The dose of danazol was increased, and the patient was instructed to take hydroxyzine as needed during episodes of swelling that were associated with pruritus.
The swelling episodes associated with pruritus occurred with variable frequency (several times per week to once every few months) but resolved within 30 minutes after the administration of hydroxyzine. Cetirizine was substituted for hydroxyzine for acute episodes. Treatment with daily loratadine and ranitidine was initiated, and the episodes of swelling with pruritus decreased in frequency.
Four months before the current presentation, swelling of the right arm developed after venipuncture. There was no associated pruritus. The patient was evaluated in the emergency department of this hospital. Ultrasonography of the arm showed no evidence of deep-vein thrombosis, and the patient was discharged from the emergency department. The swelling resolved after 3 days.
Two weeks before the current presentation, nausea, vomiting, and diarrhea developed. The patient attributed her symptoms to food poisoning, since her daughter had similar symptoms; the symptoms resolved after 3 days.
One week before the current presentation, epigastric pain developed; the pain was burning in character, worsened with consumption of food, and abated with the use of nonsteroidal antiinflammatory drugs (NSAIDs). The patient was evaluated at a fourth hospital, where CT of the abdomen reportedly revealed inflammation of the duodenum and jejunum. A proton-pump inhibitor was administered, and the abdominal pain decreased. The patient was instructed not to take NSAIDs and was discharged home. However, during the next week, abdominal pain recurred, along with new symptoms of poor appetite and early satiety. She presented to the emergency department of this hospital for further care.
Other history included hypertension, low-back pain, and osteoporosis; she had undergone previous appendectomy and cesarean section. The patient also had a subepithelial duodenal mass, measuring 7 mm in diameter, that had been stable in size during the past 5 years; ultrasonographic images had shown that the mass was consistent with a benign stromal cell neoplasm. Medications included amlodipine, calcium carbonate, cholecalciferol, omeprazole, ranitidine, loratadine, and danazol, as well as cetirizine as needed. The patient had no known medication allergies but was allergic to iodinated contrast material. She was originally from Bangladesh and now lived with her husband and two children in a suburban community in New England and worked as a teacher. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had hypertension. The patient reported no similar episodes of swelling in either of her parents.
On examination, the temperature was 36.8[degrees]C, the blood pressure 106/81 mm Hg, the pulse 74 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The abdomen was mildly distended with normal bowel sounds and diffuse tenderness on palpation, without rebound or involuntary guarding. The remainder of the physical examination was normal. The complete blood count was normal, as were blood levels of lipase, bilirubin, alkaline phosphatase, troponin, and thyrotropin. The alanine aminotransferase level was 49 IU per liter (reference range, 7 to 33), and the aspartate aminotransferase level was 52 IU per liter (reference range, 9 to 32).
Dr. Ravi Gottumukkala: CT of the abdomen and pelvis, performed without the administration of oral or intravenous contrast material, revealed long-segment marked circumferential thickening of the jejunal wall with associated mesenteric edema and small-volume free intraperitoneal fluid. The remainder of the small bowel and colon showed no abnormalities (Figure 1).	
Figure 1 
Dr. Phadke: Diagnostic tests were performed, and treatment decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 54-year-old woman with a history of episodic swelling of the arms, hands, and feet was evaluated in the emergency department of this hospital because of abdominal pain, nausea, and vomiting.
Twenty-three years before the current presentation, swelling of the left hand developed after the patient sustained a human bite. The swelling was associated with mild pruritus, erythema, and warmth. The swelling was well demarcated, involved only the left hand, and resolved after 3 days without specific treatment.
Twenty-two years before the current presentation, the patient had epigastric pain that radiated to her back, with associated nausea. Results of an upper gastrointestinal series, computed tomography (CT) of the abdomen, hepatobiliary scintigraphy, and esophagogastroduodenoscopy were reportedly normal. The abdominal pain resolved, but two similar self-limited episodes occurred during the next year. No cause for the abdominal pain was identified.
During the next 3 years, episodes of self-limited swelling occurred once per year; one episode involved the right foot, one the left hand, and one the right hand. There were no clear triggers for the episodes, although they tended to occur after exposure to cold or after minor trauma, such as scratching.
Eighteen years before the current presentation, episodes of swelling of the hands and feet began to occur on a monthly basis, and the patient was evaluated at another hospital after an episode of swelling of the left hand. A skin-biopsy specimen reportedly showed sparse superficial dermal perivascular and interstitial mixed inflammatory infiltrate and stromal edema. Treatment with prednisone was initiated. The swelling of the left hand resolved after 3 days, and the patient was referred to the allergy clinic of this hospital. Laboratory test results are shown in Table 1. A diagnosis of acquired C1 inhibitor deficiency was made on the basis of low levels of C1 esterase inhibitor, C4, and C1q. Results of serum protein electrophoresis were normal, and tests for antinuclear antibodies were negative. The patient was evaluated in the allergy clinic of a third hospital, and treatment with daily danazol was initiated. The episodes of swelling of the hands and feet resolved.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Ten years before the current presentation, episodes of swelling of the eyelids and upper lip occurred with associated pruritus. The episodes began with a sensation of facial flushing, pruritus of the scalp, and a raised pruritic rash on the face and chest; at times, these episodes were accompanied by shortness of breath, chest tightness, itchy throat, and red eyes. The patient was evaluated in the allergy clinic of the third hospital. Laboratory test results are shown in Table 1. The dose of danazol was increased, and the patient was instructed to take hydroxyzine as needed during episodes of swelling that were associated with pruritus.
The swelling episodes associated with pruritus occurred with variable frequency (several times per week to once every few months) but resolved within 30 minutes after the administration of hydroxyzine. Cetirizine was substituted for hydroxyzine for acute episodes. Treatment with daily loratadine and ranitidine was initiated, and the episodes of swelling with pruritus decreased in frequency.
Four months before the current presentation, swelling of the right arm developed after venipuncture. There was no associated pruritus. The patient was evaluated in the emergency department of this hospital. Ultrasonography of the arm showed no evidence of deep-vein thrombosis, and the patient was discharged from the emergency department. The swelling resolved after 3 days.
Two weeks before the current presentation, nausea, vomiting, and diarrhea developed. The patient attributed her symptoms to food poisoning, since her daughter had similar symptoms; the symptoms resolved after 3 days.
One week before the current presentation, epigastric pain developed; the pain was burning in character, worsened with consumption of food, and abated with the use of nonsteroidal antiinflammatory drugs (NSAIDs). The patient was evaluated at a fourth hospital, where CT of the abdomen reportedly revealed inflammation of the duodenum and jejunum. A proton-pump inhibitor was administered, and the abdominal pain decreased. The patient was instructed not to take NSAIDs and was discharged home. However, during the next week, abdominal pain recurred, along with new symptoms of poor appetite and early satiety. She presented to the emergency department of this hospital for further care.
Other history included hypertension, low-back pain, and osteoporosis; she had undergone previous appendectomy and cesarean section. The patient also had a subepithelial duodenal mass, measuring 7 mm in diameter, that had been stable in size during the past 5 years; ultrasonographic images had shown that the mass was consistent with a benign stromal cell neoplasm. Medications included amlodipine, calcium carbonate, cholecalciferol, omeprazole, ranitidine, loratadine, and danazol, as well as cetirizine as needed. The patient had no known medication allergies but was allergic to iodinated contrast material. She was originally from Bangladesh and now lived with her husband and two children in a suburban community in New England and worked as a teacher. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had hypertension. The patient reported no similar episodes of swelling in either of her parents.
On examination, the temperature was 36.8[degrees]C, the blood pressure 106/81 mm Hg, the pulse 74 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The abdomen was mildly distended with normal bowel sounds and diffuse tenderness on palpation, without rebound or involuntary guarding. The remainder of the physical examination was normal. The complete blood count was normal, as were blood levels of lipase, bilirubin, alkaline phosphatase, troponin, and thyrotropin. The alanine aminotransferase level was 49 IU per liter (reference range, 7 to 33), and the aspartate aminotransferase level was 52 IU per liter (reference range, 9 to 32).
Dr. Ravi Gottumukkala: CT of the abdomen and pelvis, performed without the administration of oral or intravenous contrast material, revealed long-segment marked circumferential thickening of the jejunal wall with associated mesenteric edema and small-volume free intraperitoneal fluid. The remainder of the small bowel and colon showed no abnormalities (Figure 1).	
Figure 1 
Dr. Phadke: Diagnostic tests were performed, and treatment decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Acquired C1 inhibitor deficiency with angioedema. The patient has a history of episodic swelling of the arms, hands, and feet, which is characteristic of angioedema. The patient's lab results showed low levels of C1 esterase inhibitor, C4, and C1q, which are indicative of acquired C1 inhibitor deficiency. The patient's symptoms improved with treatment for C1 inhibitor deficiency, further supporting this diagnosis. The recent abdominal pain, nausea, and vomiting could be due to angioedema affecting the gastrointestinal tract.""
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}",Acquired C1 inhibitor deficiency with angioedema,N,"{
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        ""role"": ""assistant"",
        ""content"": ""The patient is a 54-year-old woman with a history of episodic swelling of the arms, hands, and feet, and now presents with abdominal pain, nausea, and vomiting. She has a history of acquired C1 inhibitor deficiency, which is a rare disorder characterized by recurrent episodes of angioedema. The patient's symptoms of episodic swelling, particularly after exposure to cold or minor trauma, are consistent with this diagnosis. The patient also has a history of epigastric pain, which could be related to angioedema of the gastrointestinal tract. The recent CT scan showing long-segment marked circumferential thickening of the jejunal wall with associated mesenteric edema and small-volume free intraperitoneal fluid is also consistent with angioedema. The patient's symptoms of nausea, vomiting, and diarrhea could be due to angioedema of the gastrointestinal tract. Therefore, the most likely diagnosis is an acute episode of angioedema due to acquired C1 inhibitor deficiency. \n\nDiagnosis: Acute episode of angioedema due to acquired C1 inhibitor deficiency.""
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}",Acute episode of angioedema due to acquired C1 inhibitor deficiency,Y
10.1056/NEJMcpc2115853,"Case 7-2022: A 65-Year-Old Woman with Depression, Recurrent Falls, and Inability to Care for Herself",,Diffuse large B-cell lymphoma.,Lymphoma of the CNS,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 65-year-old woman was admitted to this hospital because of depression, recurrent falls, and difficulty caring for herself.
Four years before the current admission, the patient received a diagnosis of depression that was precipitated by psychosocial stressors. She was treated with bupropion, citalopram, and cognitive behavioral therapy. The depression was well controlled until 1 year before the current admission, when she began to have anhedonia, decreased energy, sadness, and poor concentration. She resumed cognitive behavioral therapy, but her symptoms worsened during the next 4 months, and she had suicidal ideation. The dose of bupropion was increased, and treatment with trazodone was started.
Fourteen weeks before the current admission, the patient was in a motor vehicle accident that was attributed to her falling asleep while driving. After the accident, she reported increased sadness, low energy, and inability to perform her usual activities. One week later, she fell and struck her head, and she was evaluated in the emergency department of this hospital. She reported that, before her fall, she had been feeling unsteady because of weakness in the left leg. A physical examination was normal. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed hypodensities involving the subcortical and periventricular white matter, findings consistent with chronic small-vessel disease. The patient was referred to the neurology clinic of this hospital and was discharged home.
During the next week, the patient had balance difficulties and began using a walker. When she was evaluated in the neurology clinic, she reported imbalance and occasional nausea. On examination, she had a depressed affect. Strength was assessed as 5-/5 in the proximal and distal muscles of the arms and legs. Reflexes were 1+ and symmetric at the biceps, triceps, and patellar tendons and were absent at the ankles, with downgoing toes. The gait was wide-based and unsteady, with mild dragging of the left leg. A diagnosis of postconcussive syndrome was considered, and treatment with ondansetron was started for nausea. Additional tests were performed.
Magnetic resonance imaging (MRI) of the head, performed after the administration of intravenous contrast material, revealed increased signal intensity in the pons and in a periventricular distribution on T2-weighted imaging, without associated contrast enhancement. There was a region of decreased signal intensity in the right corona radiata on a map of the apparent diffusion coefficient. Results of electroencephalography were normal, as were results of electromyography and nerve-conduction studies of the left leg. Physical therapy was recommended, and repeat MRI was planned for 6 weeks later.
Over the next 6-week period, during sessions of cognitive behavioral therapy, the patient was noted to be less talkative, with slow processing, impaired recall, and mild inattention. Repeat MRI with angiography performed 6 weeks after the first study revealed patchy hyperintensity involving the centrum semiovale, corona radiata, internal capsule, and corticospinal tract bilaterally on T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging, without contrast enhancement; the cerebral vasculature was normal.
The patient had recurrent falls without loss of consciousness and began using a wheelchair. She reported worsening sadness, anxiety, and anhedonia, and treatment with buspirone was started. On evaluation in the neurology clinic 6 weeks before the current admission, testing of leg strength yielded inconsistent results, but strength in both legs was assessed as 5-/5 with maximum effort. Dragging of the left leg was also noted to be inconsistent. There were concerns that her depression might be contributing to her neurologic changes, and further follow-up with the psychiatric service was recommended.
Five weeks before the current admission, the patient's husband brought her to the emergency department of this hospital for an evaluation of worsening memory impairment, poor self-care, and frequent falls. The patient had stopped participating in physical therapy and was spending most of the day in bed. She reported that she had lost 14 kg during the previous 4 months. Other medical history included hypertension, diabetes, and osteoarthritis of the knees. There was a history of postpartum depression 27 years earlier that had lasted for several months. Medications included amlodipine, buspirone, bupropion, cholecalciferol, citalopram, metformin, and trazodone. There were no known drug allergies. The patient lived with her husband in a suburb of Boston and worked as a teacher. She was a lifelong nonsmoker, drank alcohol only occasionally, and did not use illicit drugs. Her mother had a history of anxiety and depression in her seventh decade of life. Her sister had a history of stroke.
On examination, the patient appeared tired and disheveled, with psychomotor retardation. Strength in both legs was assessed as 5/5. She had a monoplegic gait, with buckling of the left leg, when walking down a hallway, but she had a normal gait when walking on a treadmill. Her score on the Montreal Cognitive Assessment was 25, indicating mild cognitive impairment; scores range from 0 to 30, with higher scores indicating better cognitive function. The complete blood count, results of liver-function and kidney-function tests, and blood levels of cobalamin, thyrotropin, and electrolytes were normal. Screening for syphilis, Lyme disease, and the human immunodeficiency virus was negative, as was urine toxicologic screening. After an evaluation by a neurology consultant, the patient was voluntarily admitted to the inpatient psychiatric unit.
While the patient was in the hospital, the dose of citalopram was tapered, and treatment with desvenlafaxine and amphetamine-dextroamphetamine was started; her levels of attention and wakefulness increased. She participated in group psychotherapy, cognitive behavioral therapy, and occupational and physical therapy. She continued to have variable weakness in the left leg and had three witnessed falls, during which she reportedly had fatigue and lowered herself to the ground.
On hospital day 11, the patient reported being unable to use her left arm because of weakness. Although her left arm rested across her chest for most of the day, she was observed holding her husband's hand with her left hand when saying goodbye. On evaluation by a neurology consultant, strength in the left arm was assessed as 5/5. The working diagnosis was functional neurologic disorder. On hospital day 12, the patient was discharged to a rehabilitation center.
At the rehabilitation center, the patient received physical, occupational, and speech therapy, as well as medications to treat depression. During the first week, she made progress toward independence in bathing, toileting, and grooming but had limited attention, memory, and problem solving. During the second week, she became more withdrawn. There was a paucity of speech with hypophonia, decreased attention, and less eye contact with visitors who sat on her left side than with visitors who sat on her right side. During the third week, the patient stopped answering questions and following commands. She was evaluated again in the emergency department of this hospital.
On examination, the temperature was 36.7[degrees]C, the blood pressure 141/90 mm Hg, the pulse 98 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. She was withdrawn and minimally interactive. She was able to state her name but not the date or location. She did not blink in response to threat on the left side and did not track the examiner's finger past the midline to the left. There was flattening of the left nasolabial fold. The left arm was hypertonic and held in flexion; there was no spontaneous movement of the left arm or leg, and she declined to participate in a strength examination. She did not withdraw the left arm in response to nail-bed pressure; she withdrew the left foot with antigravity movement in response to tactile stimulation.
The white-cell count was 12,940 per microliter (reference range, 4500 to 11,000), with a normal differential count. The remainder of the complete blood count was normal, as were the results of liver-function and kidney-function tests and blood levels of electrolytes.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 65-year-old woman was admitted to this hospital because of depression, recurrent falls, and difficulty caring for herself.
Four years before the current admission, the patient received a diagnosis of depression that was precipitated by psychosocial stressors. She was treated with bupropion, citalopram, and cognitive behavioral therapy. The depression was well controlled until 1 year before the current admission, when she began to have anhedonia, decreased energy, sadness, and poor concentration. She resumed cognitive behavioral therapy, but her symptoms worsened during the next 4 months, and she had suicidal ideation. The dose of bupropion was increased, and treatment with trazodone was started.
Fourteen weeks before the current admission, the patient was in a motor vehicle accident that was attributed to her falling asleep while driving. After the accident, she reported increased sadness, low energy, and inability to perform her usual activities. One week later, she fell and struck her head, and she was evaluated in the emergency department of this hospital. She reported that, before her fall, she had been feeling unsteady because of weakness in the left leg. A physical examination was normal. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed hypodensities involving the subcortical and periventricular white matter, findings consistent with chronic small-vessel disease. The patient was referred to the neurology clinic of this hospital and was discharged home.
During the next week, the patient had balance difficulties and began using a walker. When she was evaluated in the neurology clinic, she reported imbalance and occasional nausea. On examination, she had a depressed affect. Strength was assessed as 5-/5 in the proximal and distal muscles of the arms and legs. Reflexes were 1+ and symmetric at the biceps, triceps, and patellar tendons and were absent at the ankles, with downgoing toes. The gait was wide-based and unsteady, with mild dragging of the left leg. A diagnosis of postconcussive syndrome was considered, and treatment with ondansetron was started for nausea. Additional tests were performed.
Magnetic resonance imaging (MRI) of the head, performed after the administration of intravenous contrast material, revealed increased signal intensity in the pons and in a periventricular distribution on T2-weighted imaging, without associated contrast enhancement. There was a region of decreased signal intensity in the right corona radiata on a map of the apparent diffusion coefficient. Results of electroencephalography were normal, as were results of electromyography and nerve-conduction studies of the left leg. Physical therapy was recommended, and repeat MRI was planned for 6 weeks later.
Over the next 6-week period, during sessions of cognitive behavioral therapy, the patient was noted to be less talkative, with slow processing, impaired recall, and mild inattention. Repeat MRI with angiography performed 6 weeks after the first study revealed patchy hyperintensity involving the centrum semiovale, corona radiata, internal capsule, and corticospinal tract bilaterally on T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging, without contrast enhancement; the cerebral vasculature was normal.
The patient had recurrent falls without loss of consciousness and began using a wheelchair. She reported worsening sadness, anxiety, and anhedonia, and treatment with buspirone was started. On evaluation in the neurology clinic 6 weeks before the current admission, testing of leg strength yielded inconsistent results, but strength in both legs was assessed as 5-/5 with maximum effort. Dragging of the left leg was also noted to be inconsistent. There were concerns that her depression might be contributing to her neurologic changes, and further follow-up with the psychiatric service was recommended.
Five weeks before the current admission, the patient's husband brought her to the emergency department of this hospital for an evaluation of worsening memory impairment, poor self-care, and frequent falls. The patient had stopped participating in physical therapy and was spending most of the day in bed. She reported that she had lost 14 kg during the previous 4 months. Other medical history included hypertension, diabetes, and osteoarthritis of the knees. There was a history of postpartum depression 27 years earlier that had lasted for several months. Medications included amlodipine, buspirone, bupropion, cholecalciferol, citalopram, metformin, and trazodone. There were no known drug allergies. The patient lived with her husband in a suburb of Boston and worked as a teacher. She was a lifelong nonsmoker, drank alcohol only occasionally, and did not use illicit drugs. Her mother had a history of anxiety and depression in her seventh decade of life. Her sister had a history of stroke.
On examination, the patient appeared tired and disheveled, with psychomotor retardation. Strength in both legs was assessed as 5/5. She had a monoplegic gait, with buckling of the left leg, when walking down a hallway, but she had a normal gait when walking on a treadmill. Her score on the Montreal Cognitive Assessment was 25, indicating mild cognitive impairment; scores range from 0 to 30, with higher scores indicating better cognitive function. The complete blood count, results of liver-function and kidney-function tests, and blood levels of cobalamin, thyrotropin, and electrolytes were normal. Screening for syphilis, Lyme disease, and the human immunodeficiency virus was negative, as was urine toxicologic screening. After an evaluation by a neurology consultant, the patient was voluntarily admitted to the inpatient psychiatric unit.
While the patient was in the hospital, the dose of citalopram was tapered, and treatment with desvenlafaxine and amphetamine-dextroamphetamine was started; her levels of attention and wakefulness increased. She participated in group psychotherapy, cognitive behavioral therapy, and occupational and physical therapy. She continued to have variable weakness in the left leg and had three witnessed falls, during which she reportedly had fatigue and lowered herself to the ground.
On hospital day 11, the patient reported being unable to use her left arm because of weakness. Although her left arm rested across her chest for most of the day, she was observed holding her husband's hand with her left hand when saying goodbye. On evaluation by a neurology consultant, strength in the left arm was assessed as 5/5. The working diagnosis was functional neurologic disorder. On hospital day 12, the patient was discharged to a rehabilitation center.
At the rehabilitation center, the patient received physical, occupational, and speech therapy, as well as medications to treat depression. During the first week, she made progress toward independence in bathing, toileting, and grooming but had limited attention, memory, and problem solving. During the second week, she became more withdrawn. There was a paucity of speech with hypophonia, decreased attention, and less eye contact with visitors who sat on her left side than with visitors who sat on her right side. During the third week, the patient stopped answering questions and following commands. She was evaluated again in the emergency department of this hospital.
On examination, the temperature was 36.7[degrees]C, the blood pressure 141/90 mm Hg, the pulse 98 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. She was withdrawn and minimally interactive. She was able to state her name but not the date or location. She did not blink in response to threat on the left side and did not track the examiner's finger past the midline to the left. There was flattening of the left nasolabial fold. The left arm was hypertonic and held in flexion; there was no spontaneous movement of the left arm or leg, and she declined to participate in a strength examination. She did not withdraw the left arm in response to nail-bed pressure; she withdrew the left foot with antigravity movement in response to tactile stimulation.
The white-cell count was 12,940 per microliter (reference range, 4500 to 11,000), with a normal differential count. The remainder of the complete blood count was normal, as were the results of liver-function and kidney-function tests and blood levels of electrolytes.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms include depression, recurrent falls, difficulty caring for herself, anhedonia, decreased energy, sadness, poor concentration, suicidal ideation, balance difficulties, memory impairment, poor self-care, and variable weakness in the left leg. These symptoms, along with the patient's age and gender, suggest a neurological disorder. The MRI of the head revealed increased signal intensity in the pons and in a periventricular distribution on T2-weighted imaging, without associated contrast enhancement. There was a region of decreased signal intensity in the right corona radiata on a map of the apparent diffusion coefficient. These findings are consistent with a diagnosis of a neurological disorder. The patient's symptoms and the MRI findings suggest a diagnosis of a functional neurological disorder. \n\nDiagnosis: Functional Neurological Disorder.""
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}",Functional Neurological Disorder,N,"{
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        ""content"": ""The patient is a 65-year-old woman with a history of depression, presenting with worsening depression, recurrent falls, difficulty caring for herself, and progressive cognitive and motor symptoms. The differential diagnosis includes major depressive disorder with significant functional impairment, neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease, stroke, and functional neurological disorder (conversion disorder). \n\nThe patient's worsening depression, anhedonia, decreased energy, and suicidal ideation could be consistent with a severe depressive episode. However, her physical symptoms, including weakness in the left leg, balance difficulties, and recurrent falls, are not typically associated with depression alone. \n\nNeurodegenerative disorders such as Alzheimer's or Parkinson's disease could present with cognitive and motor symptoms. However, the patient's cognitive symptoms, including slow processing, impaired recall, and inattention, as well as her motor symptoms, including weakness and falls, seem to have a rapid onset and progression, which is not typical for these conditions. \n\nStroke could cause sudden onset of motor and cognitive symptoms. However, the patient's MRI did not show any acute ischemic changes, making this diagnosis less likely. \n\nFunctional neurological disorder, also known as conversion disorder, is a psychiatric condition where patients present with neurological symptoms, such as weakness, movement disorders, or sensory symptoms, that cannot be explained by a neurological or medical condition. The patient's inconsistent and variable physical findings, including the inconsistent weakness in the left leg and the ability to walk normally on a treadmill but not in the hallway, are suggestive of this condition. \n\nDiagnosis: Functional Neurological Disorder (Conversion Disorder)""
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}",Functional Neurological Disorder (Conversion Disorder),N
10.1056/NEJMcpc2115848,"Case 6-2022: A 68-Year-Old Man with Fatigue, Weight Loss, and Hyperglycemia","Sodium (mmol/liter)   133
Potassium (mmol/liter)   4.5
Chloride (mmol/liter)   92
Carbon dioxide (mmol/liter)   21
Anion gap (mmol/liter) 3–7 20
Urea nitrogen (mg/dl)   20
Creatinine (mg/dl)   0.92
Glucose (mg/dl)   505
Calcium (mg/dl)   9.6
β-Hydroxybutyrate (mmol/liter) <0.4 2.6
Venous blood gases
pH   7.39
Partial pressure of carbon dioxide (mm Hg)   38
Partial pressure of oxygen (mm Hg)   69
Urine
Color Yellow Yellow
Clarity Clear Clear
pH   5.0
Specific gravity   1.037
Glucose Negative 3+
Ketones Negative 2+
Bilirubin Negative Negative
Leukocyte esterase Negative Negative
Nitrite Negative Negative
Blood Negative Negative
Protein Negative Negative",Immune checkpoint inhibitor‚Äö√Ñ√¨induced diabetes,Immune checkpoint inhibitor–induced diabetes.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old man with metastatic melanoma was evaluated in the oncology clinic of this hospital because of fatigue and weight loss.
Six years before the current evaluation, the patient received a diagnosis of superficial spreading melanoma of the left shoulder. He was treated with a wide local excision; a biopsy of the sentinel lymph node was negative for melanoma. One year before the current evaluation, the patient began to have slurred speech and weakness in the left hand. Imaging revealed a mass lesion in the parietal lobe of the brain and another mass in the hilum of the left lung. Craniotomy with resection of the brain mass was performed; pathological examination of the resected specimen revealed findings consistent with melanoma, as did a biopsy of the lung mass. Seizures developed postoperatively, and treatment with levetiracetam was initiated. Further treatment included radiation therapy targeting the parietal resection cavity and the administration of pembrolizumab.
Four months before the current evaluation, after seven cycles of pembrolizumab, the blood thyrotropin level was 9.4 [mu]IU per milliliter (reference range, 0.4 to 5.0) and the free thyroxine level 0.9 ng per deciliter (12 pmol per liter; reference range, 0.9 to 1.8 ng per deciliter [12 to 23 pmol per liter]); treatment with levothyroxine was initiated. Three months before the current evaluation, after eight cycles of pembrolizumab, exertional angina developed, and the patient underwent coronary catheterization with placement of two drug-eluting stents. Pembrolizumab treatment was resumed 1 month later.
When the patient presented to the oncology clinic for a planned infusion of pembrolizumab, he reported a 3-week history of fatigue and a 2-week history of increased thirst and nocturia, with a need to urinate as many as three times each night. Although there was no change in appetite or eating habits, he had lost 5 kg of weight in the previous 3 weeks. There was no headache or change in vision.
On examination, the temperature was 36.4[degrees]C, the heart rate 75 beats per minute, the blood pressure 128/66 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 29.0. Heart sounds were regular, with no murmur. Lung sounds were normal. There was no leg edema. Muscle bulk was normal, as was strength in the arms and legs. There was no rash, bruising, or change in skin tone. Other history included hyperlipidemia, hypothyroidism, and coronary artery disease. Medications included aspirin, atorvastatin, clopidogrel, levetiracetam, levothyroxine, metoprolol, and pembrolizumab. He did not smoke tobacco, drink alcohol, or use illicit drugs. The patient lived in New England and was a retired police officer. His father, sister, and brother had had melanoma. There was no family history of diabetes.
A complete blood count, the results of liver-function tests, and the blood thyrotropin level were normal. The blood glucose level was 505 mg per deciliter (28.03 mmol per liter; reference range, 70 to 110 mg per deciliter [3.89 to 6.11 mmol per liter]). Other laboratory test results are shown in Table 1.	
Table 1 
The patient was sent to the emergency department of this hospital, and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old man with metastatic melanoma was evaluated in the oncology clinic of this hospital because of fatigue and weight loss.
Six years before the current evaluation, the patient received a diagnosis of superficial spreading melanoma of the left shoulder. He was treated with a wide local excision; a biopsy of the sentinel lymph node was negative for melanoma. One year before the current evaluation, the patient began to have slurred speech and weakness in the left hand. Imaging revealed a mass lesion in the parietal lobe of the brain and another mass in the hilum of the left lung. Craniotomy with resection of the brain mass was performed; pathological examination of the resected specimen revealed findings consistent with melanoma, as did a biopsy of the lung mass. Seizures developed postoperatively, and treatment with levetiracetam was initiated. Further treatment included radiation therapy targeting the parietal resection cavity and the administration of pembrolizumab.
Four months before the current evaluation, after seven cycles of pembrolizumab, the blood thyrotropin level was 9.4 [mu]IU per milliliter (reference range, 0.4 to 5.0) and the free thyroxine level 0.9 ng per deciliter (12 pmol per liter; reference range, 0.9 to 1.8 ng per deciliter [12 to 23 pmol per liter]); treatment with levothyroxine was initiated. Three months before the current evaluation, after eight cycles of pembrolizumab, exertional angina developed, and the patient underwent coronary catheterization with placement of two drug-eluting stents. Pembrolizumab treatment was resumed 1 month later.
When the patient presented to the oncology clinic for a planned infusion of pembrolizumab, he reported a 3-week history of fatigue and a 2-week history of increased thirst and nocturia, with a need to urinate as many as three times each night. Although there was no change in appetite or eating habits, he had lost 5 kg of weight in the previous 3 weeks. There was no headache or change in vision.
On examination, the temperature was 36.4[degrees]C, the heart rate 75 beats per minute, the blood pressure 128/66 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 29.0. Heart sounds were regular, with no murmur. Lung sounds were normal. There was no leg edema. Muscle bulk was normal, as was strength in the arms and legs. There was no rash, bruising, or change in skin tone. Other history included hyperlipidemia, hypothyroidism, and coronary artery disease. Medications included aspirin, atorvastatin, clopidogrel, levetiracetam, levothyroxine, metoprolol, and pembrolizumab. He did not smoke tobacco, drink alcohol, or use illicit drugs. The patient lived in New England and was a retired police officer. His father, sister, and brother had had melanoma. There was no family history of diabetes.
A complete blood count, the results of liver-function tests, and the blood thyrotropin level were normal. The blood glucose level was 505 mg per deciliter (28.03 mmol per liter; reference range, 70 to 110 mg per deciliter [3.89 to 6.11 mmol per liter]). Other laboratory test results are shown in Table 1.	
Table 1 
The patient was sent to the emergency department of this hospital, and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of metastatic melanoma and has been receiving pembrolizumab, an immune checkpoint inhibitor. He presents with symptoms of fatigue, weight loss, increased thirst, and nocturia. His blood glucose level is significantly elevated, which is indicative of hyperglycemia. These symptoms and findings are consistent with pembrolizumab-induced type 1 diabetes mellitus. Pembrolizumab can cause immune-related adverse effects, including endocrinopathies such as type 1 diabetes. The sudden onset of symptoms and the absence of a family history of diabetes further support this diagnosis.\n\nDiagnosis: Pembrolizumab-induced type 1 diabetes mellitus.""
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        ""role"": ""assistant"",
        ""content"": ""The patient is a 68-year-old man with a history of metastatic melanoma, presenting with fatigue, weight loss, increased thirst, and nocturia. His blood glucose level is significantly elevated. The differential diagnosis for this patient includes diabetes mellitus, adrenal insufficiency, and drug-induced hyperglycemia. Given the patient's symptoms of increased thirst and nocturia, as well as his significantly elevated blood glucose level, diabetes mellitus is a strong possibility. However, the patient has no family history of diabetes, which makes this diagnosis less likely. Adrenal insufficiency could also cause fatigue and weight loss, but this condition typically presents with additional symptoms such as low blood pressure and hyperpigmentation, which the patient does not have. The patient is currently being treated with pembrolizumab, a drug known to cause immune-related adverse effects, including endocrinopathies such as diabetes. Given the patient's symptoms, the timing of their onset in relation to his pembrolizumab treatment, and the absence of other likely causes, drug-induced hyperglycemia due to pembrolizumab is the most likely diagnosis.\n\nDiagnosis: Pembrolizumab-induced hyperglycemia.""
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10.1056/NEJMcpc2115852,Case 5-2022: A 65-Year-Old Woman with Rapidly Progressive Weakness in the Right Arm and Recurrent Falls,"Hemoglobin (g/dl)   — 12.9
Hematocrit (%)   — 39.2
White-cell count (per μl)   — 5670
Differential count (per μl)
Neutrophils   — 3710
Lymphocytes   — 1430
Monocytes   — 450
Eosinophils   — 40
Basophils  00 — 30
Granulocytes 0–100 — 10
Platelet count (per μl)   — 247,000
Glucose (mg/dl)   — 88
Creatinine (mg/dl)   — 0.52
Urea nitrogen (mg/dl)   — 14
Aspartate aminotransferase (U/liter)   — 38
Alanine aminotransferase (U/liter)   — 33
Alkaline phosphatase (U/liter)   — 56
Total bilirubin (mg/dl)  — 0.5
Albumin (g/dl)   — 3.4
Globulin (g/dl)   — 2.5
Thyrotropin (μIU/ml) 0.4 0 — 9.98
Free thyroxine (ng/dl) 0.9–1.9 — 1.2
Creatine kinase (U/liter)   — 132
Vitamin B12 (pg/ml) 251–911 — 1223
Folate (ng/ml) >3.9 — 8.1
Antineutrophil cytoplasmic antibody Negative Negative —
Antinuclear antibody Negative — Negative
IgG (mg/dl)   875 —
IgA (mg/dl)   178 —
IgM (mg/dl)   126 —
Serum protein electrophoresis — Normal pattern —
Treponema pallidum antibody Negative Negative —
Acetylcholine receptor binding antibody (mmol/liter) ≤0.02 0 —
Acetylcholine receptor ganglionic neuronal antibody 
(mmol/liter)
≤0.02 0 —
N-methyl-d-aspartate receptor antibody Negative Negative —
Neuronal voltage-gated potassium channel–complex 
antibody (nmol/liter)
≤0.02 0 —
Leucine-rich, glioma-inactivated 1 IgG Negative Negative —
Contactin-associated protein–like 2 IgG Negative Negative —
Glutamic acid decarboxylase 65 antibody (nmol/liter) ≤0.02 0 —
γ-Aminobutyric acid type B receptor antibody Negative Negative —
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic 
acid receptor antibody
Negative Negative —
Antineuronal nuclear antibody type 1, type 2, or type 3 <1:240 Negative —
Antiglial nuclear antibody type 1 <1:240 Negative —
Amphiphysin antibody <1:240 Negative —
Purkinje cytoplasmic antibody type 1 or type 2 <1:240 Negative —
Purkinje cytoplasmic–Tr antibody <1:240 Negative —
Calcium-channel binding antibody ≤0.03 0 —
Anti–collapsin response mediator protein 5 IgG <1:240 Negative —
Cerebrospinal fluid
Red-cell count (per μl) 0–5 0 —
Total nucleated cells (per μl) 0–5 0 —
Differential count (%)
Lymphocytes 0–100 0 —
Reactive lymphocytes 0 0 —
Plasma cells 0 0 —
Monocytes 0–100 0 —
Neutrophils 0–100 0 —
Protein (mg/dl) 5–55 15 —
Glucose (mg/dl) 50–75 63 —
Oligoclonal bands — No banding seen —
N-methyl-d-aspartate receptor antibody Negative Negative —
Neuronal voltage-gated potassium channel–complex 
antibody (nmol/liter)
0.00–0.02 0.00 —
Leucine-rich, glioma-inactivated 1 IgG Negative Negative —
Contactin-associated protein–like 2 IgG Negative Negative —
Glutamic acid decarboxylase 65 antibody (nmol/liter) ≤0.02 0.00 —
γ-Aminobutyric acid type B receptor antibody Negative Negative —
Antineuronal nuclear antibody type 1, type 2, or type 3 <1:2 Negative —
Antiglial nuclear antibody type 1 <1:2 Negative —
Purkinje cytoplasmic antibody type 1 <1:2 Negative —
Purkinje cytoplasmic–Tr antibody <1:2 Negative —
Amphiphysin antibody <1:2 Negative —
Anti‚Äö√Ñ√¨collapsin response mediator protein 5 IgG <1:2 Negative ‚Äö√Ñ√Æ",Genetic Creutzfeldt‚Äö√Ñ√¨Jakob disease.,Genetic Creutzfeldt–Jakob disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 65-year-old woman was admitted to this hospital because of rapidly progressive weakness in the right arm and recurrent falls.
Twelve years before this admission, the patient noted worsening gait and balance disturbance, which slowly progressed, and falls began to occur 5 years before this admission. Her medical history included measles encephalitis, which had been diagnosed when she was 6 years of age and had resulted in weakness on the left side, severe vision and hearing impairment, and gait and balance disturbance. After rehabilitation therapy, her balance and gait apparently normalized, but she had mild residual weakness on the left side, which resulted in a change from left-hand to right-hand dominance.
Two years before this admission, the patient was evaluated in the neurology clinic of this hospital. She reported difficulties with balance, which worsened with head turning. She reported no disequilibrium, vertigo, back pain, paresthesia, or numbness. On examination, her cognitive function was intact, and although her speech was dysarthric and hypophonic, these abnormalities could have been associated with her hearing loss. The cranial-nerve examination revealed abnormal eye movements, with square-wave jerks, saccadic pursuit, and bilateral horizontal nystagmus. The hearing and vision were severely reduced. The muscle bulk was decreased throughout, and tone was normal. Motor strength was full and symmetric in the arms and legs bilaterally, and contractures were present in the fingers of the left hand. Reflexes were reduced or absent throughout, and plantar reflexes were extensor bilaterally. Vibratory sensation was reduced at the great toes but was otherwise normal. The patient had appendicular dysmetria on both finger-to-nose testing and heel-to-shin testing that was greater on the left side than on the right side. Her gait was wide-based, and she was unable to walk with a tandem gait. The Romberg sign was present.
Needle electromyographic findings and the results of nerve-conduction studies were normal, as were findings on magnetic resonance imaging (MRI) of the head, performed before and after the administration of intravenous contrast material. MRI of the cervical and thoracic spine revealed mild multilevel degenerative disk disease without clinically significant spinal-canal stenosis. A lumbar puncture was performed; analysis of the cerebrospinal fluid (CSF) showed 0 nucleated cells per microliter (reference range, 0 to 5), and oligoclonal bands were absent. Tests of the CSF and serum for antibodies associated with autoimmune and paraneoplastic encephalitis were negative (Table 1). The patient underwent physical therapy, and her symptoms stabilized.	
Table 1 
Three months before this admission, weakness in the right hand and right arm developed. The patient initially attributed the weakness to fatigue, since it had occurred during a time of increased physical activity associated with moving to a different apartment. However, the weakness did not abate, and 2 months before this admission, she was again evaluated in the neurology clinic of this hospital. She noted difficulty with communicating in sign language and with holding objects in her right hand because of weakness and had started using her left hand to eat. She reported no neck, arm, or leg pain and no sensory loss. Her gait and balance were stable, with no recent falls.
On examination, there was reduced facial expression and reduced muscle bulk and tone throughout. The right shoulder was dropped, with weakness in the right trapezius and reduced active shoulder abduction that was limited to 70 degrees, without pain on shoulder abduction. There was predominantly proximal weakness in the right arm; the muscle strength was 4-/5 on shoulder abduction and external rotation, 4+/5 on elbow flexion, and 4/5 on elbow extension, wrist extension, and abductor digiti minimi and finger extension. The strength in the right leg was normal. There was subtle weakness on the left side that involved wrist and finger extension and great toe extension. Deep-tendon reflexes were 2+ at the right biceps and 1+ at the left biceps and were otherwise areflexic throughout. Sensation was intact in the arms, but there was decreased vibratory sensation and proprioception at the great toes; sensation was otherwise normal. Moderate appendicular dysmetria was present in the arms and legs. The patient's gait, which was assessed while she was using her white cane (the type of cane commonly used by blind or visually impaired persons), was wide-based; she took excessively large steps and reached out once to touch the wall. Neurologic examination was otherwise unchanged from the examination performed 2 years earlier. Additional studies were obtained.
Dr. Pamela W. Schaefer: MRI of the head, performed without the administration of intravenous contrast material, was reported to be normal. MRI of the cervical spine was also performed without the administration of contrast material; T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging showed signal hyperintensity in the suboccipital and paraspinal soft tissues that was consistent with edema. Areas of intrinsic hyperintense signal that were consistent with fatty atrophy were seen on T1-weighted imaging. There were diffuse degenerative changes with mild spinal-canal stenosis at C4-C5, without cord compression.
Dr. Avetisyan: Repeat needle electromyography revealed no recorded motor units in the right deltoid or infraspinatus muscles, with complex repetitive discharges in the right cervical paraspinal and deltoid muscles. Nerve-conduction studies revealed mild reduction in the amplitudes of the bilateral median and right ulnar sensory responses; the sensory responses of the right radial, bilateral antebrachial cutaneous, and bilateral medial antebrachial cutaneous nerves were normal, as were the motor responses of the right median and right ulnar nerves.
During the ensuing 2 months, the weakness in the right arm progressed rapidly, which caused the patient to have difficulty ambulating with her white cane (she was unable to walk with a standard cane), making walking unsafe after frequent falls and rendering her practically bedbound. She had no pain or numbness in her arm. She was ultimately unable to care for herself at home and was admitted to this hospital for further evaluation.
Other medical history included hypercholesterolemia and hypothyroidism. Medications included ascorbic acid, vitamin B complex, coenzyme Q10, vitamin E, calcium carbonate and cholecalciferol, and levothyroxine. There were no known drug allergies. The patient lived alone and worked for a nonprofit agency. She was a lifelong nonsmoker, drank four glasses of wine per week, and did not use illicit drugs. She reported that her father had died from Creutzfeldt-Jakob disease when he was 71 years of age, 7 months after the onset of symptoms. Her mother had Alzheimer's disease, which was diagnosed when she was in her 60s; she was currently living in a nursing home. The patient had four siblings; one had died at 46 years of age from an intracerebral hemorrhage, and her remaining three siblings were well.
On examination, the temperature was 35.7[degrees]C, the blood pressure 116/64 mm Hg, the pulse 61 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 15.8. The patient appeared emaciated but was able to sit up in a chair and hold her head up. Strength in her right arm had decreased to 2/5 on shoulder shrug, shoulder abduction, elbow flexion, and elbow extension, with 3/5 strength on wrist extension and finger flexion and extension. There was new proximal weakness in the right leg, with 4/5 strength on right hip flexion. The strength in the left arm was unchanged. Deep-tendon reflexes were 3+ at the right biceps and 2+ at the brachioradialis and were otherwise absent throughout. She had ataxia as well as occasional jerks that involved the legs (with the left leg affected to a greater extent than the right leg) and were possibly stimulus-induced. The remainder of the neurologic examination was unchanged from the last visit.
Dr. Schaefer: MRI of the head, performed before and after the administration of intravenous contrast material, revealed a new linear signal on susceptibility-weighted imaging but also a marked decrease in subtle restricted diffusion on diffusion-weighted imaging and hyperintensity on FLAIR imaging (identified in retrospect on the previous MRI) in the left frontal and left parietal lobes (Figure 1). MRI of the whole spine, performed before and after the administration of intravenous contrast material, was unchanged from previous imaging.	
Figure 1 
Dr. Avetisyan: The creatine kinase level was normal. Other laboratory test results are shown in Table 1. A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 65-year-old woman was admitted to this hospital because of rapidly progressive weakness in the right arm and recurrent falls.
Twelve years before this admission, the patient noted worsening gait and balance disturbance, which slowly progressed, and falls began to occur 5 years before this admission. Her medical history included measles encephalitis, which had been diagnosed when she was 6 years of age and had resulted in weakness on the left side, severe vision and hearing impairment, and gait and balance disturbance. After rehabilitation therapy, her balance and gait apparently normalized, but she had mild residual weakness on the left side, which resulted in a change from left-hand to right-hand dominance.
Two years before this admission, the patient was evaluated in the neurology clinic of this hospital. She reported difficulties with balance, which worsened with head turning. She reported no disequilibrium, vertigo, back pain, paresthesia, or numbness. On examination, her cognitive function was intact, and although her speech was dysarthric and hypophonic, these abnormalities could have been associated with her hearing loss. The cranial-nerve examination revealed abnormal eye movements, with square-wave jerks, saccadic pursuit, and bilateral horizontal nystagmus. The hearing and vision were severely reduced. The muscle bulk was decreased throughout, and tone was normal. Motor strength was full and symmetric in the arms and legs bilaterally, and contractures were present in the fingers of the left hand. Reflexes were reduced or absent throughout, and plantar reflexes were extensor bilaterally. Vibratory sensation was reduced at the great toes but was otherwise normal. The patient had appendicular dysmetria on both finger-to-nose testing and heel-to-shin testing that was greater on the left side than on the right side. Her gait was wide-based, and she was unable to walk with a tandem gait. The Romberg sign was present.
Needle electromyographic findings and the results of nerve-conduction studies were normal, as were findings on magnetic resonance imaging (MRI) of the head, performed before and after the administration of intravenous contrast material. MRI of the cervical and thoracic spine revealed mild multilevel degenerative disk disease without clinically significant spinal-canal stenosis. A lumbar puncture was performed; analysis of the cerebrospinal fluid (CSF) showed 0 nucleated cells per microliter (reference range, 0 to 5), and oligoclonal bands were absent. Tests of the CSF and serum for antibodies associated with autoimmune and paraneoplastic encephalitis were negative (Table 1). The patient underwent physical therapy, and her symptoms stabilized.	
Table 1 
Three months before this admission, weakness in the right hand and right arm developed. The patient initially attributed the weakness to fatigue, since it had occurred during a time of increased physical activity associated with moving to a different apartment. However, the weakness did not abate, and 2 months before this admission, she was again evaluated in the neurology clinic of this hospital. She noted difficulty with communicating in sign language and with holding objects in her right hand because of weakness and had started using her left hand to eat. She reported no neck, arm, or leg pain and no sensory loss. Her gait and balance were stable, with no recent falls.
On examination, there was reduced facial expression and reduced muscle bulk and tone throughout. The right shoulder was dropped, with weakness in the right trapezius and reduced active shoulder abduction that was limited to 70 degrees, without pain on shoulder abduction. There was predominantly proximal weakness in the right arm; the muscle strength was 4-/5 on shoulder abduction and external rotation, 4+/5 on elbow flexion, and 4/5 on elbow extension, wrist extension, and abductor digiti minimi and finger extension. The strength in the right leg was normal. There was subtle weakness on the left side that involved wrist and finger extension and great toe extension. Deep-tendon reflexes were 2+ at the right biceps and 1+ at the left biceps and were otherwise areflexic throughout. Sensation was intact in the arms, but there was decreased vibratory sensation and proprioception at the great toes; sensation was otherwise normal. Moderate appendicular dysmetria was present in the arms and legs. The patient's gait, which was assessed while she was using her white cane (the type of cane commonly used by blind or visually impaired persons), was wide-based; she took excessively large steps and reached out once to touch the wall. Neurologic examination was otherwise unchanged from the examination performed 2 years earlier. Additional studies were obtained.
Dr. Pamela W. Schaefer: MRI of the head, performed without the administration of intravenous contrast material, was reported to be normal. MRI of the cervical spine was also performed without the administration of contrast material; T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging showed signal hyperintensity in the suboccipital and paraspinal soft tissues that was consistent with edema. Areas of intrinsic hyperintense signal that were consistent with fatty atrophy were seen on T1-weighted imaging. There were diffuse degenerative changes with mild spinal-canal stenosis at C4-C5, without cord compression.
Dr. Avetisyan: Repeat needle electromyography revealed no recorded motor units in the right deltoid or infraspinatus muscles, with complex repetitive discharges in the right cervical paraspinal and deltoid muscles. Nerve-conduction studies revealed mild reduction in the amplitudes of the bilateral median and right ulnar sensory responses; the sensory responses of the right radial, bilateral antebrachial cutaneous, and bilateral medial antebrachial cutaneous nerves were normal, as were the motor responses of the right median and right ulnar nerves.
During the ensuing 2 months, the weakness in the right arm progressed rapidly, which caused the patient to have difficulty ambulating with her white cane (she was unable to walk with a standard cane), making walking unsafe after frequent falls and rendering her practically bedbound. She had no pain or numbness in her arm. She was ultimately unable to care for herself at home and was admitted to this hospital for further evaluation.
Other medical history included hypercholesterolemia and hypothyroidism. Medications included ascorbic acid, vitamin B complex, coenzyme Q10, vitamin E, calcium carbonate and cholecalciferol, and levothyroxine. There were no known drug allergies. The patient lived alone and worked for a nonprofit agency. She was a lifelong nonsmoker, drank four glasses of wine per week, and did not use illicit drugs. She reported that her father had died from Creutzfeldt-Jakob disease when he was 71 years of age, 7 months after the onset of symptoms. Her mother had Alzheimer's disease, which was diagnosed when she was in her 60s; she was currently living in a nursing home. The patient had four siblings; one had died at 46 years of age from an intracerebral hemorrhage, and her remaining three siblings were well.
On examination, the temperature was 35.7[degrees]C, the blood pressure 116/64 mm Hg, the pulse 61 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 15.8. The patient appeared emaciated but was able to sit up in a chair and hold her head up. Strength in her right arm had decreased to 2/5 on shoulder shrug, shoulder abduction, elbow flexion, and elbow extension, with 3/5 strength on wrist extension and finger flexion and extension. There was new proximal weakness in the right leg, with 4/5 strength on right hip flexion. The strength in the left arm was unchanged. Deep-tendon reflexes were 3+ at the right biceps and 2+ at the brachioradialis and were otherwise absent throughout. She had ataxia as well as occasional jerks that involved the legs (with the left leg affected to a greater extent than the right leg) and were possibly stimulus-induced. The remainder of the neurologic examination was unchanged from the last visit.
Dr. Schaefer: MRI of the head, performed before and after the administration of intravenous contrast material, revealed a new linear signal on susceptibility-weighted imaging but also a marked decrease in subtle restricted diffusion on diffusion-weighted imaging and hyperintensity on FLAIR imaging (identified in retrospect on the previous MRI) in the left frontal and left parietal lobes (Figure 1). MRI of the whole spine, performed before and after the administration of intravenous contrast material, was unchanged from previous imaging.	
Figure 1 
Dr. Avetisyan: The creatine kinase level was normal. Other laboratory test results are shown in Table 1. A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of progressive weakness, balance disturbance, and dysarthria, along with her family history of Creutzfeldt-Jakob disease, suggest a prion disease. The MRI findings of hyperintensity in the left frontal and left parietal lobes are consistent with this diagnosis. Prion diseases are a group of rare, fatal brain disorders that affect both humans and animals. In humans, prion diseases impair brain function, causing memory changes, personality changes, a decline in intellectual function (dementia), and problems with movement that worsen over time. The most common form of prion disease that affects humans is Creutzfeldt-Jakob disease.\n\nDiagnosis: Creutzfeldt-Jakob disease.""
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        ""content"": ""The patient's symptoms of progressive weakness, balance disturbance, and dysarthria, along with her abnormal eye movements and appendicular dysmetria, suggest a neurodegenerative disorder. The presence of these symptoms in the absence of sensory loss or pain points towards a motor neuron disease. The patient's family history of Creutzfeldt-Jakob disease, a prion disease, is also significant. However, her symptoms do not align with the typical rapid progression of Creutzfeldt-Jakob disease. The MRI findings of new linear signal on susceptibility-weighted imaging and a decrease in subtle restricted diffusion on diffusion-weighted imaging and hyperintensity on FLAIR imaging in the left frontal and left parietal lobes suggest some form of neurodegeneration or atrophy. Given the patient's symptoms and imaging findings, a motor neuron disease such as amyotrophic lateral sclerosis (ALS) could be considered. However, the patient's long disease course (12 years) is atypical for ALS, which usually progresses over 3-5 years. The patient's symptoms, imaging findings, and disease course are most consistent with a diagnosis of a spinocerebellar ataxia, a group of hereditary ataxias that can vary widely in symptoms and progression.\n\nDiagnosis: Spinocerebellar Ataxia.""
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}",Spinocerebellar Ataxia,N,"{
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        ""content"": ""The patient is a 65-year-old woman with a history of measles encephalitis in childhood, which resulted in residual weakness on the left side. She presents with a 12-year history of worsening gait and balance disturbance, and a recent onset of rapidly progressive weakness in the right arm. The differential diagnosis for this patient includes neurodegenerative diseases such as Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS), as well as cerebrovascular disease or a brain tumor. However, the patient's MRI of the head and spine were normal, making a brain tumor or cerebrovascular disease less likely. The patient's symptoms of balance disturbance, dysarthria, and dysmetria could suggest Parkinson's disease or multiple sclerosis, but the absence of tremor makes Parkinson's disease less likely, and the absence of oligoclonal bands in the CSF makes multiple sclerosis less likely. The patient's rapidly progressive weakness, particularly in the right arm, along with the presence of complex repetitive discharges in the right cervical paraspinal and deltoid muscles on electromyography, are suggestive of ALS. The patient's family history of Creutzfeldt-Jakob disease could suggest a prion disease, but the patient's symptoms are not typical of this condition. \n\nDiagnosis: Amyotrophic lateral sclerosis (ALS) is the most likely diagnosis.""
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}",Amyotrophic lateral sclerosis (ALS) is the most likely diagnosis,N
10.1056/NEJMcpc2107349,Case 4-2022: A 55-Year-Old Man with Bilateral Hearing Loss and Eye Redness,,Neurosyphilis.,Neurosyphilis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 55-year-old man was evaluated in the rheumatology clinic of this hospital because of bilateral hearing loss and eye redness.
The patient had been in his usual state of health until 8 weeks before the current evaluation, when a headache involving the left temple developed. A similar headache had occurred during an episode of shingles 15 years earlier. He received a prescription for a 1-week course of valacyclovir for the treatment of presumed shingles. No skin lesions developed, and the headache resolved.
Four weeks before the current evaluation, hearing loss in the left ear developed during an airplane flight. The hearing loss persisted after the flight, and the patient began to have intermittent tinnitus in the left ear and redness in both eyes. He was evaluated by an otolaryngologist at a clinic affiliated with this hospital. He reported no vertigo, otorrhea, rhinitis, or sore throat. On examination, there was redness in both eyes. The right and left auricles and external auditory canals were normal, as was the right tympanic membrane. The left tympanic membrane was retracted; there was no middle-ear effusion. Results of the Weber test were inconsistent. The Rinne test was positive bilaterally, with air conduction greater than bone conduction. There was no sinus tenderness. Nasopharyngoscopy revealed midseptal deviation to the left; the posterior aspect of the nasopharynx was normal. The remainder of the examination, including a cranial nerve examination, was normal.
An audiogram showed sloping mild-to-severe sensorineural hearing loss in both ears. Results were asymmetric at low frequencies, with more severe hearing loss in the left ear than in the right ear from 125 to 2000 Hz (Figure 1A). Word recognition was 96% with the right ear and 84% with the left ear (reference range, 80 to 100). Results of tympanometry were normal in both ears. The patient received a prescription for a 12-day tapering course of oral prednisone. Magnetic resonance imaging (MRI) of the head, performed with and without the administration of intravenous contrast material, revealed no abnormal findings.	
Figure 1 
Four weeks later, the patient was evaluated by a different otolaryngologist at the clinic affiliated with this hospital. Hearing loss had progressed. Eye redness had initially decreased after prednisone therapy was started but had subsequently recurred after prednisone therapy was stopped. On examination, there was redness in both eyes. There was no spontaneous nystagmus or gait ataxia. Sinusoidal gaze tracking was normal. The head-thrust test to the left was positive, a finding that indicates vestibular hypofunction on the left side. Results of the Romberg test were normal. The Fukuda step test was positive, with the patient rotated to the left, a finding that also indicates vestibular hypofunction on the left side. A repeat audiogram showed worsening of sensorineural hearing loss and reduction of word recognition to 90% with the right ear and 64% with the left ear (Figure 1B). Results of tympanometry were normal. The patient was referred for an urgent rheumatologic evaluation.
Three days later, in the rheumatology clinic at this hospital, the patient reported ongoing hearing loss in both ears and redness in both eyes, as well as the recent onset of imbalance. He also reported that he had had fatigue and intermittent body aches for 2 months and that he had lost 5 kg of weight over a 6-month period. There was no history of oral or genital lesions; 6 weeks earlier, a nonpruritic patchy rash had developed on his torso after he received the influenza vaccine and had rapidly resolved with the use of an oral antihistamine. There was a history of irritable bowel syndrome, diverticulosis, gastritis, allergic rhinitis, and asthma. Medications included intranasal and inhaled fluticasone, vitamin B12, and omeprazole. There were no known drug allergies. The patient lived with his wife in an urban area of New England. For the past 12 years, he had been sexually active with his wife only. He was a retired construction worker. He was a nonsmoker, drank alcohol rarely, and did not use illicit drugs.
On examination, the patient appeared well. The temperature was 36.9[degrees]C, the blood pressure 115/79 mm Hg, the heart rate 95 beats per minute, the respiratory rate 15 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. There was redness in both eyes. The finger-rub test revealed grossly reduced hearing in both ears. The Romberg test was positive when the patient's eyes were open, a finding that indicates vestibular or cerebellar hypofunction. The remainder of the examination, including skin, joint, and neurologic assessments, was normal. Blood levels of electrolytes and glucose were normal, as were results of liver-function and kidney-function tests. The complete blood count with differential count was normal. The erythrocyte sedimentation rate was 55 mm per hour (reference range, 0 to 13), and the C-reactive protein level 12.3 mg per liter (reference value,  .0). The patient was referred for an urgent ophthalmologic evaluation at this hospital, which was to take place on the same day.
On ophthalmologic evaluation, the patient reported no blurred vision, floaters, eye pain, itching, or photophobia. He wore contact lenses, which he changed daily. On examination, visual acuity was normal in both eyes. The right cornea had trace pinpoint epithelial deposits, a peripheral ring of punctate epithelial erosions, and several small confluent areas of punctate epithelial erosions centrally, with no infiltrate. The left cornea had a peripheral ring of punctate epithelial erosions and several confluent areas of punctate epithelial erosions centrally, with no infiltrate. There was evidence of anterior uveitis, with 7 cells per high-power field in the right anterior chamber and 6 to 7 cells per high-power field in the left anterior chamber. There was trace flare in both eyes.
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 55-year-old man was evaluated in the rheumatology clinic of this hospital because of bilateral hearing loss and eye redness.
The patient had been in his usual state of health until 8 weeks before the current evaluation, when a headache involving the left temple developed. A similar headache had occurred during an episode of shingles 15 years earlier. He received a prescription for a 1-week course of valacyclovir for the treatment of presumed shingles. No skin lesions developed, and the headache resolved.
Four weeks before the current evaluation, hearing loss in the left ear developed during an airplane flight. The hearing loss persisted after the flight, and the patient began to have intermittent tinnitus in the left ear and redness in both eyes. He was evaluated by an otolaryngologist at a clinic affiliated with this hospital. He reported no vertigo, otorrhea, rhinitis, or sore throat. On examination, there was redness in both eyes. The right and left auricles and external auditory canals were normal, as was the right tympanic membrane. The left tympanic membrane was retracted; there was no middle-ear effusion. Results of the Weber test were inconsistent. The Rinne test was positive bilaterally, with air conduction greater than bone conduction. There was no sinus tenderness. Nasopharyngoscopy revealed midseptal deviation to the left; the posterior aspect of the nasopharynx was normal. The remainder of the examination, including a cranial nerve examination, was normal.
An audiogram showed sloping mild-to-severe sensorineural hearing loss in both ears. Results were asymmetric at low frequencies, with more severe hearing loss in the left ear than in the right ear from 125 to 2000 Hz (Figure 1A). Word recognition was 96% with the right ear and 84% with the left ear (reference range, 80 to 100). Results of tympanometry were normal in both ears. The patient received a prescription for a 12-day tapering course of oral prednisone. Magnetic resonance imaging (MRI) of the head, performed with and without the administration of intravenous contrast material, revealed no abnormal findings.	
Figure 1 
Four weeks later, the patient was evaluated by a different otolaryngologist at the clinic affiliated with this hospital. Hearing loss had progressed. Eye redness had initially decreased after prednisone therapy was started but had subsequently recurred after prednisone therapy was stopped. On examination, there was redness in both eyes. There was no spontaneous nystagmus or gait ataxia. Sinusoidal gaze tracking was normal. The head-thrust test to the left was positive, a finding that indicates vestibular hypofunction on the left side. Results of the Romberg test were normal. The Fukuda step test was positive, with the patient rotated to the left, a finding that also indicates vestibular hypofunction on the left side. A repeat audiogram showed worsening of sensorineural hearing loss and reduction of word recognition to 90% with the right ear and 64% with the left ear (Figure 1B). Results of tympanometry were normal. The patient was referred for an urgent rheumatologic evaluation.
Three days later, in the rheumatology clinic at this hospital, the patient reported ongoing hearing loss in both ears and redness in both eyes, as well as the recent onset of imbalance. He also reported that he had had fatigue and intermittent body aches for 2 months and that he had lost 5 kg of weight over a 6-month period. There was no history of oral or genital lesions; 6 weeks earlier, a nonpruritic patchy rash had developed on his torso after he received the influenza vaccine and had rapidly resolved with the use of an oral antihistamine. There was a history of irritable bowel syndrome, diverticulosis, gastritis, allergic rhinitis, and asthma. Medications included intranasal and inhaled fluticasone, vitamin B12, and omeprazole. There were no known drug allergies. The patient lived with his wife in an urban area of New England. For the past 12 years, he had been sexually active with his wife only. He was a retired construction worker. He was a nonsmoker, drank alcohol rarely, and did not use illicit drugs.
On examination, the patient appeared well. The temperature was 36.9[degrees]C, the blood pressure 115/79 mm Hg, the heart rate 95 beats per minute, the respiratory rate 15 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. There was redness in both eyes. The finger-rub test revealed grossly reduced hearing in both ears. The Romberg test was positive when the patient's eyes were open, a finding that indicates vestibular or cerebellar hypofunction. The remainder of the examination, including skin, joint, and neurologic assessments, was normal. Blood levels of electrolytes and glucose were normal, as were results of liver-function and kidney-function tests. The complete blood count with differential count was normal. The erythrocyte sedimentation rate was 55 mm per hour (reference range, 0 to 13), and the C-reactive protein level 12.3 mg per liter (reference value,  .0). The patient was referred for an urgent ophthalmologic evaluation at this hospital, which was to take place on the same day.
On ophthalmologic evaluation, the patient reported no blurred vision, floaters, eye pain, itching, or photophobia. He wore contact lenses, which he changed daily. On examination, visual acuity was normal in both eyes. The right cornea had trace pinpoint epithelial deposits, a peripheral ring of punctate epithelial erosions, and several small confluent areas of punctate epithelial erosions centrally, with no infiltrate. The left cornea had a peripheral ring of punctate epithelial erosions and several confluent areas of punctate epithelial erosions centrally, with no infiltrate. There was evidence of anterior uveitis, with 7 cells per high-power field in the right anterior chamber and 6 to 7 cells per high-power field in the left anterior chamber. There was trace flare in both eyes.
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with bilateral hearing loss, eye redness, headaches, and recent onset of imbalance. He also reports fatigue, body aches, and weight loss. The patient's symptoms, along with the findings of anterior uveitis on ophthalmologic evaluation, suggest an autoimmune or inflammatory condition. The patient's history of shingles and the recent use of valacyclovir, a medication used to treat viral infections, may suggest a viral cause, but the lack of skin lesions and the resolution of the headache argue against this. The patient's hearing loss is sensorineural, which is often caused by damage to the inner ear or nerve pathways, and can be associated with autoimmune diseases. The patient's eye redness and anterior uveitis could be associated with several autoimmune conditions, including rheumatoid arthritis, lupus, or sarcoidosis. However, the patient's lack of joint symptoms and normal blood tests argue against these diagnoses. The patient's symptoms, along with the findings of vestibular hypofunction, suggest a diagnosis of Cogan's syndrome, a rare autoimmune disorder characterized by eye inflammation and vestibular symptoms, including hearing loss and vertigo.\n\nDiagnosis: Cogan's syndrome.""
      },
      ""finish_reason"": ""stop""
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}",Cogan's syndrome,N,"{
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        ""content"": ""The patient is a 55-year-old man presenting with bilateral hearing loss, eye redness, headaches, fatigue, body aches, and weight loss. The differential diagnosis for this patient includes autoimmune diseases such as rheumatoid arthritis or lupus, infectious diseases such as Lyme disease or syphilis, and vasculitis conditions such as Wegener's granulomatosis or Cogan's syndrome. The patient's history of shingles and recent airplane travel could suggest an infectious cause, but the lack of other typical symptoms such as fever or rash makes this less likely. The patient's symptoms of hearing loss, eye redness, and headaches could be indicative of an autoimmune disease, but the lack of joint pain or skin rash makes rheumatoid arthritis or lupus less likely. The patient's symptoms of hearing loss, eye redness, and headaches, along with his elevated erythrocyte sedimentation rate and C-reactive protein level, are indicative of a vasculitis condition. The patient's symptoms are most consistent with Cogan's syndrome, which is characterized by eye inflammation and audiovestibular symptoms. \n\nDiagnosis: Cogan's syndrome.""
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}",Cogan's syndrome,N
10.1056/NEJMcpc2115850,"Case 3-2022: A 14-Year-Old Boy with Fever, Joint Pain, and Abdominal Cramping","Hemoglobin (g/dl) 13.0–16.0 12.6
Hematocrit (%) 37.0–49.0 38.9
Platelet count (per μl)   419,000
White-cell count (per μl) 450 ,000 12,950
Differential count (per μl)
Neutrophils 180 100 8530
Lymphocytes 1200–5200 2330
Monocytes 30 00 1640
Eosinophils 0–1000 350
Basophils  0 50
Erythrocyte sedimentation rate (mm/hr)   48
C-reactive protein (mg/liter) 0. .0 207.6
Alanine aminotransferase (U/liter)   9
Aspartate aminotransferase (U/liter)   9
Alkaline phosphatase (U/liter) 55–149 81
Lipase (U/liter) 13–60 82
Albumin (g/dl)   3.1
Sodium (mmol/liter)   138
Potassium (mmol/liter)   3.8
Chloride (mmol/liter)   102
Carbon dioxide (mmol/liter)   26
Urea nitrogen (mg/dl)   8
Creatinine (mg/dl)   0.72",Inflammatory bowel disease (Crohn’s disease),Inflammatory bowel disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 14-year-old boy was admitted to this hospital because of fatigue, fever, joint pain, abdominal cramping, and diarrhea.
The patient had been well until 2 weeks before this admission, when fatigue and fever developed on his final day of summer camp. He was taken to the primary care clinic at another hospital and was told that he had a viral infection.
Nine days before this admission, new mild sore throat developed, and the patient returned to the primary care clinic. A throat culture for group A beta-hemolytic streptococcus was reportedly negative. The patient was told that he had possible sinusitis, and treatment with amoxicillin-clavulanate was started. During the next 3 days, the sore throat abated, but fatigue and fever persisted.
Six days before this admission, new pain in the right shoulder and left knee developed, and the patient again returned to the primary care clinic. The white-cell count and erythrocyte sedimentation rate were reportedly elevated; a blood test for Lyme disease was performed.
On the day of admission, the joint pain progressed to involve the shoulders and knees on both sides, and the temperature increased to 39.4[degrees]C. The patient was given ibuprofen and brought to the emergency department at this hospital. On evaluation, the patient described aching pain in the shoulders and knees, which was worst in his right shoulder and left knee. He rated the pain at 7 on a scale of 0 to 10, with 10 indicating the most severe pain. He had not noticed redness, swelling, or stiffness of the joints. A review of systems was notable for chills, intermittent night sweats, headache, myalgias, and lightheadedness when he stood up from a sitting position. He had no weight loss, rash, vision changes, or respiratory symptoms. He had mild abdominal cramping, decreased appetite, and intermittent nausea. During the past week, there had been a few episodes of nonbloody emesis and watery diarrhea. There had been no hematemesis, hematochezia, or melena.
The patient had autism spectrum disorder, with an early delay in speech development that had resolved after speech therapy. He had met milestones for gross and fine motor skills and growth. He had reportedly received all routine childhood vaccinations. Other history included asthma, seasonal rhinosinusitis, and allergies to peanuts and tree nuts; there were no known drug allergies. He had undergone a tonsillectomy in early childhood. Medications included amoxicillin-clavulanate, inhaled fluticasone, and ibuprofen and inhaled albuterol as needed.
At the time of admission, the patient was on his summer break before entering high school. Earlier in the summer, he had gone on vacation to a coastal area of New England. He had also attended camp in a rural area of New England, where he camped and hiked in wooded areas and swam in fresh water. He had seen a tick on his clothing but did not recall any bites. Two weeks before this admission, the patient had returned to his home in a suburban area of New England, where he lived with his mother (who was a veterinarian), father, sister, and pet dog. His sister had recently had an acute gastrointestinal illness that resolved after several days. The patient was not sexually active and did not use alcohol, drugs, or tobacco. His mother had hypothyroidism, and his maternal uncle had rheumatoid arthritis; there was no other known family history of autoimmune diseases.
On examination, the temperature was 36.1[degrees]C, the blood pressure 128/58 mm Hg, the heart rate 107 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 27.2. The patient appeared to be well developed and well nourished, but he looked tired. The conjunctivae were normal. The mucous membranes were dry, and there was an aphthous ulcer on the right buccal mucosa. The lungs were clear on auscultation. There was tenderness on palpation of the epigastric and periumbilical abdomen. There was no erythema, warmth, swelling, or crepitus of the large and small joints. There was tenderness on palpation, as well as pain with movement, of the right shoulder and knees; range of motion in these joints was not decreased. The patient had no rash or lymphadenopathy.
The white-cell count was 12,950 per microliter (reference range, 4500 to 13,000), the erythrocyte sedimentation rate 48 mm per hour (reference range, 0 to 13), the C-reactive protein level 207.6 mg per liter (reference range, 0.0 to 8.0), and the lipase level 82 U per liter (reference range, 13 to 60). Laboratory test results are shown in Table 1.	
Table 1 
While the patient was in the emergency department, the temperature increased to 39.2[degrees]C. Intravenous fluids were administered, and empirical treatment with doxycycline was started. The patient was admitted to the hospital.
During the next 2 days, the fever resolved, but the joint pain, abdominal cramping, and diarrhea worsened in severity. On the third hospital day, fever recurred. The white-cell count was 15,190 per microliter, the C-reactive protein level 178.3 mg per liter, and the lipase level 145 U per liter. A fecal occult blood test was positive. A plain film of the right shoulder was normal.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 14-year-old boy was admitted to this hospital because of fatigue, fever, joint pain, abdominal cramping, and diarrhea.
The patient had been well until 2 weeks before this admission, when fatigue and fever developed on his final day of summer camp. He was taken to the primary care clinic at another hospital and was told that he had a viral infection.
Nine days before this admission, new mild sore throat developed, and the patient returned to the primary care clinic. A throat culture for group A beta-hemolytic streptococcus was reportedly negative. The patient was told that he had possible sinusitis, and treatment with amoxicillin-clavulanate was started. During the next 3 days, the sore throat abated, but fatigue and fever persisted.
Six days before this admission, new pain in the right shoulder and left knee developed, and the patient again returned to the primary care clinic. The white-cell count and erythrocyte sedimentation rate were reportedly elevated; a blood test for Lyme disease was performed.
On the day of admission, the joint pain progressed to involve the shoulders and knees on both sides, and the temperature increased to 39.4[degrees]C. The patient was given ibuprofen and brought to the emergency department at this hospital. On evaluation, the patient described aching pain in the shoulders and knees, which was worst in his right shoulder and left knee. He rated the pain at 7 on a scale of 0 to 10, with 10 indicating the most severe pain. He had not noticed redness, swelling, or stiffness of the joints. A review of systems was notable for chills, intermittent night sweats, headache, myalgias, and lightheadedness when he stood up from a sitting position. He had no weight loss, rash, vision changes, or respiratory symptoms. He had mild abdominal cramping, decreased appetite, and intermittent nausea. During the past week, there had been a few episodes of nonbloody emesis and watery diarrhea. There had been no hematemesis, hematochezia, or melena.
The patient had autism spectrum disorder, with an early delay in speech development that had resolved after speech therapy. He had met milestones for gross and fine motor skills and growth. He had reportedly received all routine childhood vaccinations. Other history included asthma, seasonal rhinosinusitis, and allergies to peanuts and tree nuts; there were no known drug allergies. He had undergone a tonsillectomy in early childhood. Medications included amoxicillin-clavulanate, inhaled fluticasone, and ibuprofen and inhaled albuterol as needed.
At the time of admission, the patient was on his summer break before entering high school. Earlier in the summer, he had gone on vacation to a coastal area of New England. He had also attended camp in a rural area of New England, where he camped and hiked in wooded areas and swam in fresh water. He had seen a tick on his clothing but did not recall any bites. Two weeks before this admission, the patient had returned to his home in a suburban area of New England, where he lived with his mother (who was a veterinarian), father, sister, and pet dog. His sister had recently had an acute gastrointestinal illness that resolved after several days. The patient was not sexually active and did not use alcohol, drugs, or tobacco. His mother had hypothyroidism, and his maternal uncle had rheumatoid arthritis; there was no other known family history of autoimmune diseases.
On examination, the temperature was 36.1[degrees]C, the blood pressure 128/58 mm Hg, the heart rate 107 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 27.2. The patient appeared to be well developed and well nourished, but he looked tired. The conjunctivae were normal. The mucous membranes were dry, and there was an aphthous ulcer on the right buccal mucosa. The lungs were clear on auscultation. There was tenderness on palpation of the epigastric and periumbilical abdomen. There was no erythema, warmth, swelling, or crepitus of the large and small joints. There was tenderness on palpation, as well as pain with movement, of the right shoulder and knees; range of motion in these joints was not decreased. The patient had no rash or lymphadenopathy.
The white-cell count was 12,950 per microliter (reference range, 4500 to 13,000), the erythrocyte sedimentation rate 48 mm per hour (reference range, 0 to 13), the C-reactive protein level 207.6 mg per liter (reference range, 0.0 to 8.0), and the lipase level 82 U per liter (reference range, 13 to 60). Laboratory test results are shown in Table 1.	
Table 1 
While the patient was in the emergency department, the temperature increased to 39.2[degrees]C. Intravenous fluids were administered, and empirical treatment with doxycycline was started. The patient was admitted to the hospital.
During the next 2 days, the fever resolved, but the joint pain, abdominal cramping, and diarrhea worsened in severity. On the third hospital day, fever recurred. The white-cell count was 15,190 per microliter, the C-reactive protein level 178.3 mg per liter, and the lipase level 145 U per liter. A fecal occult blood test was positive. A plain film of the right shoulder was normal.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fatigue, fever, joint pain, abdominal cramping, and diarrhea, along with the history of camping and hiking in wooded areas, suggest a possible tick-borne illness. The patient's elevated white-cell count and erythrocyte sedimentation rate indicate an ongoing inflammatory response. The patient's negative throat culture for group A beta-hemolytic streptococcus and lack of response to amoxicillin-clavulanate suggest that his symptoms are not due to a bacterial infection of the throat. The patient's joint pain and fever could be due to Lyme disease, but his blood test for Lyme disease was not mentioned as positive. The patient's abdominal cramping and diarrhea, along with a positive fecal occult blood test, suggest a gastrointestinal infection. Given the patient's history of camping and hiking in wooded areas, a tick-borne illness that can cause gastrointestinal symptoms, such as Anaplasmosis or Babesiosis, should be considered. However, the patient's symptoms and lab findings are most consistent with a diagnosis of Campylobacter jejuni infection, which can cause diarrhea, abdominal cramping, fever, and joint pain, and is often associated with camping and exposure to untreated water.\n\nDiagnosis: Campylobacter jejuni infection.""
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        ""content"": ""The patient's symptoms of fatigue, fever, joint pain, abdominal cramping, and diarrhea, along with the elevated white-cell count and erythrocyte sedimentation rate, suggest an inflammatory or infectious process. The patient's recent history of camping and hiking in wooded areas, along with the fact that he had seen a tick on his clothing, raises the possibility of a tick-borne illness such as Lyme disease. However, the patient's blood test for Lyme disease was reportedly negative. The patient's abdominal symptoms, along with the positive fecal occult blood test, suggest a gastrointestinal pathology. The patient's history of autism spectrum disorder and allergies, along with the family history of autoimmune disease (rheumatoid arthritis in a maternal uncle), raise the possibility of an autoimmune condition. The presence of an aphthous ulcer in the mouth can be seen in inflammatory bowel disease (IBD), specifically Crohn's disease, which can present with gastrointestinal symptoms, joint pain, and fever. The elevated C-reactive protein level and erythrocyte sedimentation rate further support a diagnosis of IBD. \n\nDiagnosis: Crohn's disease.""
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        ""content"": ""The patient is a 14-year-old boy presenting with fatigue, fever, joint pain, abdominal cramping, and diarrhea. He also has a history of exposure to wooded areas and a tick sighting, which raises the possibility of a tick-borne illness such as Lyme disease. However, his blood test for Lyme disease was negative. He also has an elevated white cell count and erythrocyte sedimentation rate, indicating an ongoing inflammatory or infectious process. His symptoms of joint pain and fever could also suggest a rheumatologic condition, such as juvenile idiopathic arthritis or lupus, especially given the family history of rheumatoid arthritis. However, he does not have other common symptoms of these conditions, such as a rash or kidney problems. His gastrointestinal symptoms, including abdominal cramping and diarrhea, could suggest a condition like inflammatory bowel disease, but this would not typically cause joint pain or fever. Given his recent exposure to wooded areas and the presence of fever, fatigue, joint pain, and gastrointestinal symptoms, a tick-borne illness is still a strong possibility despite the negative Lyme disease test. There are other tick-borne diseases, such as anaplasmosis or babesiosis, that could cause his symptoms. \n\nDiagnosis: Tick-borne illness, possibly anaplasmosis or babesiosis.""
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10.1056/NEJMcpc2115847,Case 2-2022: A 70-Year-Old Man with a Recurrent Left Pleural Effusion,"Hemoglobin (g/dl)   12.4 11.1
Hematocrit (%)   37.1 33.7
Mean corpuscular volume (fl)   108.5 112.7
White-cell count (per μl)   5700 3030
Differential count (%)
Neutrophils   80.4 49.6
Lymphocytes   7.7 32.3
Monocytes   6.5 12.5
Eosinophils   1.2 2
Basophils   0.7 1
Platelet count (per μl)   165,000 246,000
Erythrocyte sedimentation rate (mm/hr)   55 107
C-reactive protein (mg/liter)   88.7 205.8
Lactate dehydrogenase (U/liter) 11 10 192 —
Total protein (g/dl) 6. .3 7.2 7.4
Pleural fluid
Lactate dehydrogenase (U/liter) — 195 —
Total protein (g/dl) — 4.8 —
Albumin (g/dl) — 3.3 —
Glucose (mg/dl) — 111 —
Red-cell count (per μl) — 55,000 —
Total nucleated cells (per μl) — 2742 —
Differential count (%)
Neutrophils 0 30 —
Lymphocytes 0 51 —
Macrophages 0 11 —
Monocytes 0 2 —
Eosinophils 0 3 —
Basophils 0 1 —
Unclassified cells 0 2 —","VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.","VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old man was evaluated in the rheumatology clinic of this hospital because of a recurrent left pleural effusion.
Five years before this presentation, the patient had pain in the shoulders and proximal muscles of the arms and legs. The pain was worse in the morning and was associated with fatigue. There was no associated stiffness. The erythrocyte sedimentation rate and the C-reactive protein level were elevated. Prednisone was initiated for the treatment of a working diagnosis of polymyalgia rheumatica, and symptoms abated quickly. During the next year, attempts to discontinue prednisone led to recurrent myalgias, as well as elevations in the erythrocyte sedimentation rate and the C-reactive protein level.
Three years before this presentation, swelling, erythema, and pain developed in the cartilaginous portion of the left ear, sparing the earlobe (Figure 1). There was no reduction in these symptoms after empirical antibacterial therapy was initiated for the treatment of presumed cellulitis. The dose of prednisone was increased, and the symptoms involving the ear resolved; however, they recurred when the dose of prednisone was tapered. Biopsy of the left auricle revealed perichondrial inflammation and degenerative changes in the cartilage. The dose of prednisone was increased for a presumed diagnosis of relapsing polychondritis. The symptoms involving the ear resolved, and weekly therapy with methotrexate was initiated.	
Figure 1 
During the next 6 months, attempts to taper the prednisone dose were associated with worsening inflammatory joint and cartilage symptoms, along with elevations in the erythrocyte sedimentation rate and the C-reactive protein level. The erythrocyte sedimentation rate was as high as 89 mm per hour (reference range, 0 to 13) and the C-reactive protein level as high as 73.6 mg per liter (reference value,  .0).
Two years before this presentation, the patient began treatment with tocilizumab for fatigue, markedly elevated C-reactive protein level, and elevated erythrocyte sedimentation rate, all of which persisted despite treatment with prednisone and methotrexate. The administration of tocilizumab allowed for the tapering of prednisone to a lower dose without causing an exacerbation of inflammatory joint and cartilage symptoms. Two weeks after the patient began receiving tocilizumab therapy, and upon tapering of the prednisone dose, pain and swelling developed in the right leg; ultrasound examination revealed a distal deep-vein thrombosis in the right posterior tibial vein. Repeat ultrasonography of the leg performed 2 weeks later did not show propagation of the deep-vein thrombosis, and the pain and swelling resolved with the continued use of a compression stocking and elevation of the right leg. However, 2 months later, when further tapering of the prednisone dose was started, inflammatory joint and cartilage symptoms recurred, and pain and swelling developed in the left leg. Ultrasound examination revealed deep-vein thromboses in the left popliteal and left calf veins and in the right femoral vein; therapy with rivaroxaban was initiated. The development of recurrent deep-vein thromboses was attributed to the underlying inflammatory disease. The dose of prednisone was increased, methotrexate was continued, and tocilizumab was replaced with infliximab therapy.
During the next 6 months, the inflammatory joint and cartilage symptoms worsened when attempts were made to taper the prednisone dose, and these conditions abated only when the dose of prednisone was increased. Blood tests for antineutrophil cytoplasmic antibodies (ANCAs), rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were negative. Fifteen months before this presentation, treatment with rituximab was initiated. However, after an attempt to taper the dose of prednisone, bilateral scleritis developed (Figure 1); the dose of prednisone was increased again, which resulted in resolution of the ocular pain and redness. During the next 3 months, attempts to taper the prednisone dose resulted in recurrent episodes of scleritis and inflammatory joint and cartilage symptoms; additional rituximab treatment was not administered.
One year before the current presentation, treatment with low-dose cyclophosphamide was initiated, but the use of this medication was complicated by severe neutropenia, which did not allow for the dose to be escalated. Nine months before this presentation, treatment with cyclophosphamide was stopped, and intravenous tocilizumab was restarted, given its previous efficacy in this patient. However, the use of tocilizumab also resulted in moderate but transient neutropenia after each infusion.
Seven months before this presentation, pleuritic chest pain on the lower left side developed, along with dyspnea on exertion and a dry cough. Chest radiography revealed a moderate left pleural effusion (Figure 2A and 2B). Thoracentesis was performed, and 1 liter of straw-colored pleural fluid was removed; laboratory test results are shown in Table 1. Gram's staining of the pleural fluid revealed abundant polymorphonuclear cells but no organisms; bacterial, fungal, and mycobacterial cultures were without growth. Cytologic examination of the pleural fluid revealed no malignant cells. Computed tomography (CT) of the chest (performed after the pleural fluid was drained) showed a small left pleural effusion, a trace right pleural effusion, and bibasilar dependent atelectasis without consolidation, nodules, or lymphadenopathy (Figure 2C). The pleural effusions were attributed to ongoing inflammatory disease. The dose of prednisone was increased, and the pleurisy and dyspnea resolved. Five months before this presentation, tocilizumab therapy was stopped, and tofacitinib was initiated. One week before this presentation, the patient had sudden onset of back pain on the left side. Imaging studies were performed.	
Figure 2 	Table 1 
Dr. Vincent V. Dinculescu: CT of the chest and abdomen, performed 6 months after the first CT of the chest, revealed a small left pleural effusion that was larger than it had been on the first chest CT (Figure 2D). A punctate stone in the lower pole of the left kidney was also observed, with no evidence of hydronephrosis.
Dr. Perugino: The patient presented to the rheumatology clinic for further evaluation. He had no dyspnea, cough, or fever. On examination, the temperature was 36.7[degrees]C, the heart rate 64 beats per minute, the blood pressure 145/75 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 29.2. There was no scleral redness or erythema of the helix of the ear. The heart sounds were regular. Breath sounds were decreased at the base of the left lung. There was no leg edema, joint swelling or tenderness, purpura, petechiae, or deficits in motor strength.
The patient had a history of mucinous adenocarcinoma of the cecum, which had been diagnosed 10 years before this presentation and had been treated with laparoscopic colectomy of the right side of the colon and with oxaliplatin therapy, without evidence of recurrence. Other history included peripheral neuropathy (attributed to the oxaliplatin therapy), hypothyroidism, and monoclonal gammopathy of undetermined significance. Macrocytic anemia had been present for 3 years before this presentation, with normal blood levels of cobalamin and folate. The patient also had a history of leukopenia and neutropenia; these conditions had occurred intermittently over the course of the 10 years preceding this presentation but were most pronounced after treatment with cyclophosphamide and tocilizumab. Medications included alendronate, atorvastatin, cholecalciferol, folic acid, levothyroxine, methotrexate, omeprazole, prednisone, rivaroxaban, trimethoprim-sulfamethoxazole, and tofacitinib. The patient drank alcohol occasionally; he did not smoke tobacco or use illicit drugs. He lived in New England and was retired. There was no family history of autoimmune disease.
The blood levels of electrolytes, glucose, and thyrotropin were normal, as were the results of liver-function and kidney-function tests. Testing for antinuclear antibodies was negative. Other laboratory test results are shown in Table 1.
A diagnostic test was performed, and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old man was evaluated in the rheumatology clinic of this hospital because of a recurrent left pleural effusion.
Five years before this presentation, the patient had pain in the shoulders and proximal muscles of the arms and legs. The pain was worse in the morning and was associated with fatigue. There was no associated stiffness. The erythrocyte sedimentation rate and the C-reactive protein level were elevated. Prednisone was initiated for the treatment of a working diagnosis of polymyalgia rheumatica, and symptoms abated quickly. During the next year, attempts to discontinue prednisone led to recurrent myalgias, as well as elevations in the erythrocyte sedimentation rate and the C-reactive protein level.
Three years before this presentation, swelling, erythema, and pain developed in the cartilaginous portion of the left ear, sparing the earlobe (Figure 1). There was no reduction in these symptoms after empirical antibacterial therapy was initiated for the treatment of presumed cellulitis. The dose of prednisone was increased, and the symptoms involving the ear resolved; however, they recurred when the dose of prednisone was tapered. Biopsy of the left auricle revealed perichondrial inflammation and degenerative changes in the cartilage. The dose of prednisone was increased for a presumed diagnosis of relapsing polychondritis. The symptoms involving the ear resolved, and weekly therapy with methotrexate was initiated.	
Figure 1 
During the next 6 months, attempts to taper the prednisone dose were associated with worsening inflammatory joint and cartilage symptoms, along with elevations in the erythrocyte sedimentation rate and the C-reactive protein level. The erythrocyte sedimentation rate was as high as 89 mm per hour (reference range, 0 to 13) and the C-reactive protein level as high as 73.6 mg per liter (reference value,  .0).
Two years before this presentation, the patient began treatment with tocilizumab for fatigue, markedly elevated C-reactive protein level, and elevated erythrocyte sedimentation rate, all of which persisted despite treatment with prednisone and methotrexate. The administration of tocilizumab allowed for the tapering of prednisone to a lower dose without causing an exacerbation of inflammatory joint and cartilage symptoms. Two weeks after the patient began receiving tocilizumab therapy, and upon tapering of the prednisone dose, pain and swelling developed in the right leg; ultrasound examination revealed a distal deep-vein thrombosis in the right posterior tibial vein. Repeat ultrasonography of the leg performed 2 weeks later did not show propagation of the deep-vein thrombosis, and the pain and swelling resolved with the continued use of a compression stocking and elevation of the right leg. However, 2 months later, when further tapering of the prednisone dose was started, inflammatory joint and cartilage symptoms recurred, and pain and swelling developed in the left leg. Ultrasound examination revealed deep-vein thromboses in the left popliteal and left calf veins and in the right femoral vein; therapy with rivaroxaban was initiated. The development of recurrent deep-vein thromboses was attributed to the underlying inflammatory disease. The dose of prednisone was increased, methotrexate was continued, and tocilizumab was replaced with infliximab therapy.
During the next 6 months, the inflammatory joint and cartilage symptoms worsened when attempts were made to taper the prednisone dose, and these conditions abated only when the dose of prednisone was increased. Blood tests for antineutrophil cytoplasmic antibodies (ANCAs), rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were negative. Fifteen months before this presentation, treatment with rituximab was initiated. However, after an attempt to taper the dose of prednisone, bilateral scleritis developed (Figure 1); the dose of prednisone was increased again, which resulted in resolution of the ocular pain and redness. During the next 3 months, attempts to taper the prednisone dose resulted in recurrent episodes of scleritis and inflammatory joint and cartilage symptoms; additional rituximab treatment was not administered.
One year before the current presentation, treatment with low-dose cyclophosphamide was initiated, but the use of this medication was complicated by severe neutropenia, which did not allow for the dose to be escalated. Nine months before this presentation, treatment with cyclophosphamide was stopped, and intravenous tocilizumab was restarted, given its previous efficacy in this patient. However, the use of tocilizumab also resulted in moderate but transient neutropenia after each infusion.
Seven months before this presentation, pleuritic chest pain on the lower left side developed, along with dyspnea on exertion and a dry cough. Chest radiography revealed a moderate left pleural effusion (Figure 2A and 2B). Thoracentesis was performed, and 1 liter of straw-colored pleural fluid was removed; laboratory test results are shown in Table 1. Gram's staining of the pleural fluid revealed abundant polymorphonuclear cells but no organisms; bacterial, fungal, and mycobacterial cultures were without growth. Cytologic examination of the pleural fluid revealed no malignant cells. Computed tomography (CT) of the chest (performed after the pleural fluid was drained) showed a small left pleural effusion, a trace right pleural effusion, and bibasilar dependent atelectasis without consolidation, nodules, or lymphadenopathy (Figure 2C). The pleural effusions were attributed to ongoing inflammatory disease. The dose of prednisone was increased, and the pleurisy and dyspnea resolved. Five months before this presentation, tocilizumab therapy was stopped, and tofacitinib was initiated. One week before this presentation, the patient had sudden onset of back pain on the left side. Imaging studies were performed.	
Figure 2 	Table 1 
Dr. Vincent V. Dinculescu: CT of the chest and abdomen, performed 6 months after the first CT of the chest, revealed a small left pleural effusion that was larger than it had been on the first chest CT (Figure 2D). A punctate stone in the lower pole of the left kidney was also observed, with no evidence of hydronephrosis.
Dr. Perugino: The patient presented to the rheumatology clinic for further evaluation. He had no dyspnea, cough, or fever. On examination, the temperature was 36.7[degrees]C, the heart rate 64 beats per minute, the blood pressure 145/75 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 29.2. There was no scleral redness or erythema of the helix of the ear. The heart sounds were regular. Breath sounds were decreased at the base of the left lung. There was no leg edema, joint swelling or tenderness, purpura, petechiae, or deficits in motor strength.
The patient had a history of mucinous adenocarcinoma of the cecum, which had been diagnosed 10 years before this presentation and had been treated with laparoscopic colectomy of the right side of the colon and with oxaliplatin therapy, without evidence of recurrence. Other history included peripheral neuropathy (attributed to the oxaliplatin therapy), hypothyroidism, and monoclonal gammopathy of undetermined significance. Macrocytic anemia had been present for 3 years before this presentation, with normal blood levels of cobalamin and folate. The patient also had a history of leukopenia and neutropenia; these conditions had occurred intermittently over the course of the 10 years preceding this presentation but were most pronounced after treatment with cyclophosphamide and tocilizumab. Medications included alendronate, atorvastatin, cholecalciferol, folic acid, levothyroxine, methotrexate, omeprazole, prednisone, rivaroxaban, trimethoprim-sulfamethoxazole, and tofacitinib. The patient drank alcohol occasionally; he did not smoke tobacco or use illicit drugs. He lived in New England and was retired. There was no family history of autoimmune disease.
The blood levels of electrolytes, glucose, and thyrotropin were normal, as were the results of liver-function and kidney-function tests. Testing for antinuclear antibodies was negative. Other laboratory test results are shown in Table 1.
A diagnostic test was performed, and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Relapsing Polychondritis. The patient's history of recurrent inflammation of the cartilage in the ear, along with joint pain and inflammation, elevated erythrocyte sedimentation rate and C-reactive protein level, and the response to prednisone treatment, are all indicative of this condition. The recurrent pleural effusion could also be a manifestation of this disease. The negative results for antineutrophil cytoplasmic antibodies, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies help to rule out other autoimmune conditions.""
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        ""content"": ""Relapsing Polychondritis. The patient's history of recurrent inflammation of the cartilage in the ear, along with joint pain and inflammation, elevated erythrocyte sedimentation rate and C-reactive protein level, and response to prednisone treatment, are all consistent with this condition. The recurrent pleural effusion could also be a manifestation of this systemic disease. The negative results for antineutrophil cytoplasmic antibodies (ANCAs), rheumatoid factor, and anti-cyclic citrullinated peptide antibodies help to rule out other autoimmune conditions.""
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        ""content"": ""The patient is a 70-year-old man with a history of polymyalgia rheumatica, relapsing polychondritis, and recurrent deep-vein thromboses. He presents with recurrent left pleural effusion. The differential diagnosis for this patient includes autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and vasculitis; malignancies such as lung cancer and lymphoma; and infections such as tuberculosis and pneumonia. The patient's history of polymyalgia rheumatica and relapsing polychondritis, along with negative tests for antineutrophil cytoplasmic antibodies (ANCAs), rheumatoid factor, and anti-cyclic citrullinated peptide antibodies, make SLE, RA, and vasculitis less likely. The patient's history of mucinous adenocarcinoma of the cecum, which was treated 10 years ago, raises the possibility of a malignancy, but the cytologic examination of the pleural fluid revealed no malignant cells, making lung cancer and lymphoma less likely. The patient's lack of fever and the negative bacterial, fungal, and mycobacterial cultures of the pleural fluid make an infection less likely. The patient's history of recurrent deep-vein thromboses and the presence of a punctate stone in the lower pole of the left kidney on imaging suggest a possible connection between the patient's recurrent left pleural effusion and his history of thromboses and kidney stone. \n\nDiagnosis: Recurrent left pleural effusion secondary to underlying inflammatory disease.""
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}",Recurrent left pleural effusion secondary to underlying inflammatory disease.,N
10.1056/NEJMcpc2115844,Case 1-2022: A 67-Year-Old Man with Motor Neuron Disease and Odd Behaviors during Sleep,,Anti-IgLON5 IgG–associated neurologic disorder.,Anti-IgLON5 disease,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 67-year-old man was evaluated in the sleep clinic at this hospital because of odd behaviors during sleep, daytime sleepiness, and apnea detected on a home sleep study.
Three years before the current evaluation, the patient's wife noticed that the patient had vocalizations, including talking and yelling, while sleeping. He also had thrashing movements while sleeping; he fell out of bed more than once and inadvertently hit his wife during these movements.
Two years before the current evaluation, the patient's wife noticed that the patient had prolonged episodes of daytime sleepiness. During the episodes, he appeared to fall asleep while sitting up and was unresponsive to shaking and loud voices; several hours later, he returned to normal interaction without any intervention. The daytime sleepiness was intermittent and fluctuated in severity.
Four months before the current evaluation, the patient fell asleep while washing dishes. This resulted in a fall and unstable C1 spinal fracture, which required urgent surgical repair. After the surgical repair, melatonin and trazodone were prescribed for insomnia, and abnormal movements during sleep abated. However, vocalizations during sleep - including singing, talking, and expression of fear and anger in the context of upsetting dreams - continued and were most prominent in the early morning hours.
The patient also had a motor neurologic syndrome that had started before the onset of sleep symptoms, approximately 3.5 years before the current evaluation. Symptoms included progressive gait imbalance with falls, hand clumsiness, hoarse voice, and dysphagia. Serial neurologic examinations, performed over a 3-year period by multiple neuromuscular specialists, revealed slow progression of generalized fasciculations and the development of bulbar hyperreflexia, postural instability, and hypophonia, although strength in the arms and legs remained intact. Serial electromyography revealed progressive and widespread involvement of muscles showing chronic reinnervation changes, including eventual involvement of craniobulbar muscles (tongue and masseter muscles).
Dr. Brian Zhao: One year before the current evaluation, magnetic resonance imaging (MRI) of the cervical spine revealed moderate neural foraminal narrowing at the level of C3-C4 bilaterally and no central canal stenosis. Four months before the current evaluation, MRI of the head revealed a punctate subacute infarct in the left posterior centrum semiovale, chronic infarcts in the left middle frontal gyrus and right cerebellum, and nonspecific moderate-to-severe white-matter changes (Figure 1).	
Figure 1
Dr. Babu: Blood tests for paraneoplastic, nutritional, and paraproteinemic causes of the patient's neurologic syndrome were unrevealing. A diagnosis of slowly progressive motor neuron disease was made, and therapy with riluzole was begun. A videofluoroscopic swallowing study revealed severe oropharyngeal dysphagia with laryngeal penetration and silent aspiration; a gastrostomy tube was placed, and tube feeding was initiated.
The patient underwent a home sleep-apnea test, which showed sleep-disordered breathing with an apnea-hypopnea index of 20 events per hour; hypoxemia was present at rest while he was breathing ambient air. Severe oxygen desaturation occurred with frequent respiratory events while he was asleep in the supine position. The patient was then referred to the sleep clinic for an initial evaluation.
On evaluation in the sleep clinic, the patient reported that obstructive sleep apnea had been diagnosed on the basis of a home sleep study performed 1 year earlier. Multiple attempts at treatment with continuous positive airway pressure (CPAP) had been unsuccessful; there had been difficulty in finding a mask that fit comfortably.
In addition to the sleep and motor neurologic syndrome described previously, the patient's symptoms included snoring, difficulty with sleep initiation, forgetfulness, poor judgment regarding his ability to safely complete physical tasks, urinary urgency and frequency, and night sweats. He had a history of type 2 diabetes mellitus, which was well controlled with insulin and had been complicated by mild, stable, length-dependent sensory polyneuropathy; other history included hyperlipidemia, a heterozygous factor V Leiden mutation, depression, orthostatic hypotension, and gastroesophageal reflux disease. Medications included alprazolam, bupropion, fenofibrate, insulin, melatonin, metformin, riluzole, sertraline, and trazodone; there were no known drug allergies. The patient lived in New England with his wife. He was a retired engineer. He drank two alcoholic beverages per day. He did not smoke tobacco or use illicit drugs. His mother had died from an unknown cause at an elderly age; his father had died from trauma. One of his brothers had cerebrovascular disease, and another had schizophrenia.
On examination, the temperature was 36.6[degrees]C, the blood pressure 112/60 mm Hg, the pulse 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.2. The patient was awake, alert, and oriented, although his attention was somewhat diminished. He could recall two words out of three. Naming and repetition were intact. The pupils were equally reactive to light and accommodation. Extraocular movements were intact, and visual fields were full. Facial sensation and strength were normal. Speech was hypophonic and mildly slurred. Elevation of the palate was symmetric, and movement of the tongue was normal. Shoulder shrug was symmetric. Strength was 5/5 in all muscle groups. Deep-tendon reflexes were brisk in the arms, with mild spasticity in the legs. Plantar responses were normal. Vibratory sensation in the legs was mildly diminished. Results of finger-to-nose and heel-to-shin testing were normal. There were mild myoclonic movements in both hands. Alternating movements were mildly clumsy. Tone was slightly increased in the legs. The gait was on a narrow base and was unsteady; the patient was unable to walk with a tandem gait. The Romberg test showed truncal titubation.
A sleep study to determine the appropriate positive airway pressure (PAP) therapy was performed. In CPAP mode, there was good control of respiratory events. Electromyographic signals revealed elevated muscle tone during rapid-eye-movement (REM) sleep, but there were no abnormal behaviors.
Two weeks later, during a follow-up visit in the neuromuscular clinic, the patient became unresponsive to sternal rub; the vital signs and blood glucose level were normal. He was transported to the emergency department, where he returned to a normal level of consciousness without intervention. Electroencephalography (EEG) revealed frequent intermittent diffuse polymorphic delta slowing of the background, often with bifrontal predominance, but showed no epileptiform abnormalities. The patient was fitted with a mask for CPAP, and treatment was initiated. Several weeks after the initiation of treatment, download of CPAP data revealed good effectiveness and adherence.
However, episodes of unresponsiveness increased in frequency and lasted up to 3 hours at a time. During the episodes, the patient's wife was unable to arouse him despite performing a sternal rub. Modafinil was prescribed, but the episodes did not abate. The patient was admitted to the epilepsy monitoring unit for long-term monitoring and EEG. During the admission, two episodes of unresponsiveness occurred, during which the patient had a normal blood pressure, heart rate, and glucose level and EEG revealed findings consistent with sleep.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 67-year-old man was evaluated in the sleep clinic at this hospital because of odd behaviors during sleep, daytime sleepiness, and apnea detected on a home sleep study.
Three years before the current evaluation, the patient's wife noticed that the patient had vocalizations, including talking and yelling, while sleeping. He also had thrashing movements while sleeping; he fell out of bed more than once and inadvertently hit his wife during these movements.
Two years before the current evaluation, the patient's wife noticed that the patient had prolonged episodes of daytime sleepiness. During the episodes, he appeared to fall asleep while sitting up and was unresponsive to shaking and loud voices; several hours later, he returned to normal interaction without any intervention. The daytime sleepiness was intermittent and fluctuated in severity.
Four months before the current evaluation, the patient fell asleep while washing dishes. This resulted in a fall and unstable C1 spinal fracture, which required urgent surgical repair. After the surgical repair, melatonin and trazodone were prescribed for insomnia, and abnormal movements during sleep abated. However, vocalizations during sleep - including singing, talking, and expression of fear and anger in the context of upsetting dreams - continued and were most prominent in the early morning hours.
The patient also had a motor neurologic syndrome that had started before the onset of sleep symptoms, approximately 3.5 years before the current evaluation. Symptoms included progressive gait imbalance with falls, hand clumsiness, hoarse voice, and dysphagia. Serial neurologic examinations, performed over a 3-year period by multiple neuromuscular specialists, revealed slow progression of generalized fasciculations and the development of bulbar hyperreflexia, postural instability, and hypophonia, although strength in the arms and legs remained intact. Serial electromyography revealed progressive and widespread involvement of muscles showing chronic reinnervation changes, including eventual involvement of craniobulbar muscles (tongue and masseter muscles).
Dr. Brian Zhao: One year before the current evaluation, magnetic resonance imaging (MRI) of the cervical spine revealed moderate neural foraminal narrowing at the level of C3-C4 bilaterally and no central canal stenosis. Four months before the current evaluation, MRI of the head revealed a punctate subacute infarct in the left posterior centrum semiovale, chronic infarcts in the left middle frontal gyrus and right cerebellum, and nonspecific moderate-to-severe white-matter changes (Figure 1).	
Figure 1
Dr. Babu: Blood tests for paraneoplastic, nutritional, and paraproteinemic causes of the patient's neurologic syndrome were unrevealing. A diagnosis of slowly progressive motor neuron disease was made, and therapy with riluzole was begun. A videofluoroscopic swallowing study revealed severe oropharyngeal dysphagia with laryngeal penetration and silent aspiration; a gastrostomy tube was placed, and tube feeding was initiated.
The patient underwent a home sleep-apnea test, which showed sleep-disordered breathing with an apnea-hypopnea index of 20 events per hour; hypoxemia was present at rest while he was breathing ambient air. Severe oxygen desaturation occurred with frequent respiratory events while he was asleep in the supine position. The patient was then referred to the sleep clinic for an initial evaluation.
On evaluation in the sleep clinic, the patient reported that obstructive sleep apnea had been diagnosed on the basis of a home sleep study performed 1 year earlier. Multiple attempts at treatment with continuous positive airway pressure (CPAP) had been unsuccessful; there had been difficulty in finding a mask that fit comfortably.
In addition to the sleep and motor neurologic syndrome described previously, the patient's symptoms included snoring, difficulty with sleep initiation, forgetfulness, poor judgment regarding his ability to safely complete physical tasks, urinary urgency and frequency, and night sweats. He had a history of type 2 diabetes mellitus, which was well controlled with insulin and had been complicated by mild, stable, length-dependent sensory polyneuropathy; other history included hyperlipidemia, a heterozygous factor V Leiden mutation, depression, orthostatic hypotension, and gastroesophageal reflux disease. Medications included alprazolam, bupropion, fenofibrate, insulin, melatonin, metformin, riluzole, sertraline, and trazodone; there were no known drug allergies. The patient lived in New England with his wife. He was a retired engineer. He drank two alcoholic beverages per day. He did not smoke tobacco or use illicit drugs. His mother had died from an unknown cause at an elderly age; his father had died from trauma. One of his brothers had cerebrovascular disease, and another had schizophrenia.
On examination, the temperature was 36.6[degrees]C, the blood pressure 112/60 mm Hg, the pulse 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.2. The patient was awake, alert, and oriented, although his attention was somewhat diminished. He could recall two words out of three. Naming and repetition were intact. The pupils were equally reactive to light and accommodation. Extraocular movements were intact, and visual fields were full. Facial sensation and strength were normal. Speech was hypophonic and mildly slurred. Elevation of the palate was symmetric, and movement of the tongue was normal. Shoulder shrug was symmetric. Strength was 5/5 in all muscle groups. Deep-tendon reflexes were brisk in the arms, with mild spasticity in the legs. Plantar responses were normal. Vibratory sensation in the legs was mildly diminished. Results of finger-to-nose and heel-to-shin testing were normal. There were mild myoclonic movements in both hands. Alternating movements were mildly clumsy. Tone was slightly increased in the legs. The gait was on a narrow base and was unsteady; the patient was unable to walk with a tandem gait. The Romberg test showed truncal titubation.
A sleep study to determine the appropriate positive airway pressure (PAP) therapy was performed. In CPAP mode, there was good control of respiratory events. Electromyographic signals revealed elevated muscle tone during rapid-eye-movement (REM) sleep, but there were no abnormal behaviors.
Two weeks later, during a follow-up visit in the neuromuscular clinic, the patient became unresponsive to sternal rub; the vital signs and blood glucose level were normal. He was transported to the emergency department, where he returned to a normal level of consciousness without intervention. Electroencephalography (EEG) revealed frequent intermittent diffuse polymorphic delta slowing of the background, often with bifrontal predominance, but showed no epileptiform abnormalities. The patient was fitted with a mask for CPAP, and treatment was initiated. Several weeks after the initiation of treatment, download of CPAP data revealed good effectiveness and adherence.
However, episodes of unresponsiveness increased in frequency and lasted up to 3 hours at a time. During the episodes, the patient's wife was unable to arouse him despite performing a sternal rub. Modafinil was prescribed, but the episodes did not abate. The patient was admitted to the epilepsy monitoring unit for long-term monitoring and EEG. During the admission, two episodes of unresponsiveness occurred, during which the patient had a normal blood pressure, heart rate, and glucose level and EEG revealed findings consistent with sleep.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms include vocalizations and thrashing movements during sleep, daytime sleepiness, and apnea. These symptoms are consistent with REM sleep behavior disorder (RBD), a condition characterized by the loss of normal voluntary muscle atonia during REM sleep, leading to physical activity associated with dreaming. The patient's motor neurologic syndrome, including progressive gait imbalance, hand clumsiness, hoarse voice, and dysphagia, along with the findings of generalized fasciculations and bulbar hyperreflexia, suggest a neurodegenerative disorder. The patient's episodes of unresponsiveness, during which he appears to fall asleep and is unresponsive to external stimuli, are consistent with narcolepsy, a neurological disorder that affects the control of sleep and wakefulness. However, the patient's neurologic syndrome and the progression of his symptoms suggest a diagnosis of a neurodegenerative disorder, such as amyotrophic lateral sclerosis (ALS), which can present with bulbar symptoms and is associated with RBD. The patient's sleep study results, which showed good control of respiratory events with CPAP, support the diagnosis of sleep apnea, a common comorbidity in patients with neurodegenerative disorders. Therefore, the patient's symptoms and test results suggest a diagnosis of ALS with comorbid RBD and sleep apnea. \n\nDiagnosis: Amyotrophic lateral sclerosis with comorbid REM sleep behavior disorder and sleep apnea.""
      },
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}","{
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    {
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      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient's symptoms include vocalizations, thrashing movements, and falling out of bed during sleep, as well as prolonged episodes of daytime sleepiness during which he appears to fall asleep and is unresponsive. These symptoms suggest a sleep disorder. The patient also has a motor neurologic syndrome that includes progressive gait imbalance, hand clumsiness, hoarse voice, and dysphagia. These symptoms suggest a neurodegenerative disorder. The patient's sleep study showed sleep-disordered breathing with an apnea-hypopnea index of 20 events per hour, indicating sleep apnea. However, the patient's episodes of unresponsiveness, during which he cannot be aroused and EEG findings are consistent with sleep, suggest a diagnosis of narcolepsy. The patient's motor symptoms, including generalized fasciculations, bulbar hyperreflexia, postural instability, and hypophonia, along with the results of electromyography showing progressive and widespread involvement of muscles showing chronic reinnervation changes, suggest a diagnosis of motor neuron disease. \n\nDiagnosis: Motor Neuron Disease with Comorbid Narcolepsy and Sleep Apnea.""
      },
      ""finish_reason"": ""stop""
    }
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  ""usage"": {
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}",Motor Neuron Disease with Comorbid Narcolepsy and Sleep Apnea,N,"{
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  ""object"": ""chat.completion"",
  ""created"": 1690696623,
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    {
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        ""content"": ""The patient is a 67-year-old man presenting with abnormal behaviors during sleep, daytime sleepiness, and apnea. He has a history of vocalizations and thrashing movements during sleep, and has fallen out of bed multiple times. He also has episodes of daytime sleepiness where he appears to fall asleep and is unresponsive for several hours. He has a history of type 2 diabetes mellitus, hyperlipidemia, a heterozygous factor V Leiden mutation, depression, orthostatic hypotension, and gastroesophageal reflux disease. The differential diagnosis for this patient includes sleep apnea, narcolepsy, REM sleep behavior disorder, and neurodegenerative disorders such as Parkinson's disease or dementia with Lewy bodies. The patient has been diagnosed with obstructive sleep apnea based on a home sleep study, but treatment with CPAP has been unsuccessful. His motor neurologic syndrome, including progressive gait imbalance, hand clumsiness, hoarse voice, and dysphagia, along with generalized fasciculations and bulbar hyperreflexia, suggest a neurodegenerative disorder. The patient's episodes of unresponsiveness, during which EEG revealed findings consistent with sleep, suggest narcolepsy. However, the presence of vocalizations and thrashing movements during sleep, which are most prominent in the early morning hours, suggest REM sleep behavior disorder. Given the patient's age, the presence of a motor neurologic syndrome, and the symptoms of REM sleep behavior disorder, the most likely diagnosis is dementia with Lewy bodies.\n\nDiagnosis: Dementia with Lewy bodies.""
      },
      ""finish_reason"": ""stop""
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}",Dementia with Lewy bodies,N
10.1056/NEJMcpc2107358,"Case 40-2021: A 9-Year-Old Boy with Transient Weakness, Facial Droop, and Slurred Speech",,Moyamoya disease,Transient ischemic attack due to moyamoya disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 9-year-old boy was transferred to this hospital because of transient weakness and facial droop on the left side and slurred speech.
The patient had been well until 5 hours before this evaluation, when his parents observed that he had a facial droop on the left side and slurred speech. In addition, the patient noticed that his left arm and leg felt ""limp."" When he moved to get out of his bed, he could not stand on his own or grip using the left hand. There was no confusion, loss of consciousness, shaking in the arms or legs, urinary or fecal incontinence, headache, nausea, vomiting, recent illness, or trauma. The symptoms lasted approximately 2 minutes and then resolved completely. Emergency medical services were called, and the patient was taken to the emergency department of another hospital.
At the other hospital, the physical examination was reportedly normal. The complete blood count, erythrocyte sedimentation rate, prothrombin time, partial-thromboplastin time, and blood levels of electrolytes, glucose, and troponin were normal, as were the results of tests of renal, liver, and thyroid function. The patient was transferred to this hospital for further evaluation.
On arrival at this hospital, additional history was obtained from the patient's parents. Earlier in the day, the patient had become upset while visiting his grandfather, who was dying of esophageal cancer. He then played a game of hockey with a sibling; no falls or head trauma occurred. At the time that his parents observed the new neurologic symptoms, he had been lying in bed and crying profusely and inconsolably for an extended period. His parents noticed that he was gasping for air and hiccupping while crying.
The patient had been born by normal spontaneous vaginal delivery at full term. He had met normal developmental milestones and had received routine childhood vaccinations. He had chronic gastrointestinal upset that had been attributed to anxiety. Two years earlier, he had been evaluated at the neurology clinic of another hospital because of episodes of shaking in the arms and legs, which occurred multiple times a day. The shaking occurred more frequently when the patient was excited or emotional. He was aware of the shaking; he felt an urge before each episode, and the urge was relieved after the shaking occurred. His parents were told that the shaking was stereotypy, and no diagnostic tests were performed.
The patient took no medications and had no known drug allergies. He lived with his parents and two siblings in a suburban area of New England. He attended elementary school and performed well academically, although he received tutoring for mild difficulties with reading and phonology. In addition to the history of esophageal cancer in his paternal grandfather, his father had ulcerative colitis, his mother had received a diagnosis of large-B-cell lymphoma in childhood, his sister had asthma, and his maternal grandfather had died of acute coronary syndrome at 30 years of age.
On evaluation, the patient appeared well developed and mildly anxious. The temperature was 37.2[degrees]C, the blood pressure 116/64 mm Hg, the pulse 91 beats per minute, the respiratory rate 26 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The face was symmetric, with normal forehead wrinkling, blinking, smiling, and cheek puffing. An evaluation of other cranial-nerve functions, sensation, power, bulk, tone, coordination, and gait was normal.
A diagnostic test result was reviewed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 9-year-old boy was transferred to this hospital because of transient weakness and facial droop on the left side and slurred speech.
The patient had been well until 5 hours before this evaluation, when his parents observed that he had a facial droop on the left side and slurred speech. In addition, the patient noticed that his left arm and leg felt ""limp."" When he moved to get out of his bed, he could not stand on his own or grip using the left hand. There was no confusion, loss of consciousness, shaking in the arms or legs, urinary or fecal incontinence, headache, nausea, vomiting, recent illness, or trauma. The symptoms lasted approximately 2 minutes and then resolved completely. Emergency medical services were called, and the patient was taken to the emergency department of another hospital.
At the other hospital, the physical examination was reportedly normal. The complete blood count, erythrocyte sedimentation rate, prothrombin time, partial-thromboplastin time, and blood levels of electrolytes, glucose, and troponin were normal, as were the results of tests of renal, liver, and thyroid function. The patient was transferred to this hospital for further evaluation.
On arrival at this hospital, additional history was obtained from the patient's parents. Earlier in the day, the patient had become upset while visiting his grandfather, who was dying of esophageal cancer. He then played a game of hockey with a sibling; no falls or head trauma occurred. At the time that his parents observed the new neurologic symptoms, he had been lying in bed and crying profusely and inconsolably for an extended period. His parents noticed that he was gasping for air and hiccupping while crying.
The patient had been born by normal spontaneous vaginal delivery at full term. He had met normal developmental milestones and had received routine childhood vaccinations. He had chronic gastrointestinal upset that had been attributed to anxiety. Two years earlier, he had been evaluated at the neurology clinic of another hospital because of episodes of shaking in the arms and legs, which occurred multiple times a day. The shaking occurred more frequently when the patient was excited or emotional. He was aware of the shaking; he felt an urge before each episode, and the urge was relieved after the shaking occurred. His parents were told that the shaking was stereotypy, and no diagnostic tests were performed.
The patient took no medications and had no known drug allergies. He lived with his parents and two siblings in a suburban area of New England. He attended elementary school and performed well academically, although he received tutoring for mild difficulties with reading and phonology. In addition to the history of esophageal cancer in his paternal grandfather, his father had ulcerative colitis, his mother had received a diagnosis of large-B-cell lymphoma in childhood, his sister had asthma, and his maternal grandfather had died of acute coronary syndrome at 30 years of age.
On evaluation, the patient appeared well developed and mildly anxious. The temperature was 37.2[degrees]C, the blood pressure 116/64 mm Hg, the pulse 91 beats per minute, the respiratory rate 26 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The face was symmetric, with normal forehead wrinkling, blinking, smiling, and cheek puffing. An evaluation of other cranial-nerve functions, sensation, power, bulk, tone, coordination, and gait was normal.
A diagnostic test result was reviewed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of transient weakness, facial droop on the left side, and slurred speech are indicative of a transient ischemic attack (TIA) or stroke. However, these symptoms resolved completely within 2 minutes, which is unusually quick for a TIA or stroke. The patient's symptoms occurred during a period of intense emotional distress, during which he was gasping for air and hiccupping. This suggests that the patient may have been hyperventilating, which can cause symptoms similar to those of a TIA or stroke due to reduced blood flow to the brain. The patient's history of episodes of shaking in the arms and legs, which occur more frequently when he is excited or emotional, further supports a diagnosis related to anxiety or emotional distress rather than a neurological condition. Therefore, the most likely diagnosis is hyperventilation syndrome.\n\nDiagnosis: Hyperventilation syndrome.""
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  ""created"": 1690696668,
  ""model"": ""gpt-4-0613"",
  ""choices"": [
    {
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      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient's symptoms of transient weakness and facial droop on the left side, slurred speech, and inability to stand or grip with his left hand are indicative of a transient ischemic attack (TIA) or stroke. However, these are very rare in children and usually associated with specific risk factors such as sickle cell disease, congenital heart disease, or coagulation disorders, none of which are mentioned in the case. The symptoms occurred during a period of intense emotional upset and crying, which can cause hyperventilation. Hyperventilation can lead to respiratory alkalosis, which can cause cerebral vasoconstriction and lead to transient neurologic symptoms similar to those seen in a TIA or stroke. The patient's history of episodes of shaking in the arms and legs, which occur more frequently when he is excited or emotional, could also be related to hyperventilation. \n\nDiagnosis: Hyperventilation syndrome.""
      },
      ""finish_reason"": ""stop""
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  ""usage"": {
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    ""completion_tokens"": 190,
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}",Hyperventilation syndrom,N,"{
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  ""object"": ""chat.completion"",
  ""created"": 1690696706,
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  ""choices"": [
    {
      ""index"": 0,
      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient is a 9-year-old boy who presented with transient weakness and facial droop on the left side and slurred speech. These symptoms are suggestive of a neurological event such as a transient ischemic attack (TIA) or stroke. However, these conditions are extremely rare in children and usually associated with underlying conditions such as sickle cell disease, congenital heart disease, or coagulation disorders, none of which are mentioned in the patient's history. Other possible causes of these symptoms include seizures, migraines, or conversion disorder. The patient's history of stereotypy, which is a repetitive or ritualistic movement, posture, or utterance, suggests a possible neurological or psychiatric condition. The fact that the symptoms occurred during a period of intense emotional distress and resolved completely within minutes makes a psychological cause more likely. The patient's chronic gastrointestinal upset attributed to anxiety also supports this. Therefore, the most likely diagnosis is conversion disorder, also known as functional neurological symptom disorder, where patients present with physical neurological symptoms not explained by a neurological disease or other medical condition.\n\nDiagnosis: Conversion disorder.""
      },
      ""finish_reason"": ""stop""
    }
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  ""usage"": {
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    ""total_tokens"": 2902
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}",Conversion disorder,N
10.1056/NEJMcpc2107355,Case 39-2021: A 26-Year-Old Woman with Respiratory Failure and Altered Mental Status,"Hemoglobin (g/dl) 12. .2 9.1   9.2
Hematocrit (%) 34.1–44.9 26.3   27.6
White-cell count (per μl) 3900–10,800 21,800   17,670
Differential count (%)
Neutrophils 43–74 82   92.7
Lymphocytes 17–44 8.4   4.4
Monocytes 4–13 8.3   1.7
Eosinophils 1–10 0.6   0.0
Platelet count (per μl) 154,00 69,000 201,000   221,000
Albumin (g/dl) 2.5 3.5–4.8   3.1
Lactate (mmol/liter)   4.5   1.6
Procalcitonin (ng/ml) <0.10 3.09 0.00–0.08 1.59
Troponin I (ng/ml) <0.029 0.65 — —
High-sensitivity troponin T (ng/liter) — — <0.03 237
B-type natriuretic peptide (pg/ml) 0–100 395 — —
N-terminal pro–B-type natriuretic peptide (pg/ml) — — <450 1865
Erythrocyte sedimentation rate (mm/hr) — —   63
C-reactive protein (mg/liter) — —   204.8
Triglycerides (mg/dl) — —  0 167
Arterial blood gas
Fraction of inspired oxygen — — — 1.00
pH — —   7.44
Partial pressure of carbon dioxide (mm Hg) — —   39
Partial pressure of oxygen (mm Hg) — —   116",Fat embolism syndrome.,Fat embolism syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 26-year-old woman was transferred to this hospital because of respiratory failure and altered mental status.
The patient had been in her usual state of health until 3 days before the current admission, when she underwent elective abdominoplasty and liposuction at an ambulatory surgery center. During the procedure, anesthetic agents included intravenous propofol, fentanyl, midazolam, and ketamine, as well as local lidocaine injections. During recovery after the procedure, medications included intravenous cefazolin, enoxaparin, and ondansetron; oral oxycodone, tramadol, and gabapentin; and transdermal scopolamine. The patient was lethargic after the procedure but was able to be discharged home after a period of observation.
Later that day, the patient was instructed by telephone to take a lower dose of postoperative oxycodone. The next day, on evaluation at the surgical center, she was found to be somnolent but arousable and able to answer questions with effort; the scopolamine patch was removed. Several hours after the patient returned home, her family noticed that she had increased respiratory effort and minimal responsiveness. She was taken by ambulance to the emergency department of a local hospital.
In the emergency department, the temperature was 37.7[degrees]C, the heart rate 130 beats per minute, the blood pressure 121/77 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 83% while the patient was breathing ambient air. She was lethargic, moaned intermittently, and responded with one-word answers; symmetric movement in the arms and legs was observed. Intravenous naloxone was administered, with minor improvement in her condition. Levels of electrolytes and results of kidney- and liver-function tests were normal; other laboratory test results are shown in Table 1. An electrocardiogram showed sinus tachycardia, rightward axis deviation, and nonspecific ST-T-wave changes.	
Table 1 
Dr. Dexter P. Mendoza: A chest radiograph showed diffuse confluent opacities in both lungs (Figure 1A). Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material as part of a pulmonary-embolism protocol, ruled out pulmonary embolism but revealed diffuse mixed ground-glass and consolidative opacities involving all lobes of the lungs, with relative sparing of the subpleural lung (Figure 1B). CT of the abdomen revealed postoperative changes. CT of the head, performed without the administration of contrast material, revealed mild effacement of the cerebral sulci and cisterns on both sides, a finding suggestive of mild diffuse cerebral edema (Figure 1C and 1D). There was also a small hypodensity in the left globus pallidus, a finding suggestive of infarction.	
Figure 1 
Dr. Shah: Noninvasive bilevel positive airway pressure was initiated, and the patient was admitted to the intensive care unit (ICU) at the other hospital. Intravenous vancomycin, piperacillin-tazobactam, levofloxacin, and oseltamivir were administered empirically, and a triple-lumen central venous catheter was inserted.
The next morning, the findings on a repeat chest radiograph appeared to be unchanged, but the patient had progressive lethargy, so intubation was performed and mechanical ventilation was initiated. Pink frothy secretions were noted. Intravenous methylprednisolone, propofol, and norepinephrine were administered. A nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was negative. The troponin I level increased to 4.31 ng per milliliter (reference range, <0.029). The thyrotropin, carboxyhemoglobin, and lipase levels were normal, and tests for Legionella pneumophila and Streptococcus pneumoniae urinary antigens were negative.
Later that afternoon, the patient was transferred to the ICU at this hospital. A review of systems was unavailable because intubation was performed on arrival. Medical history that was obtained from family members included iron-deficiency anemia, anxiety disorder, insomnia, and two normal spontaneous vaginal deliveries. Regular medications included lorazepam as needed for sleep; postoperative medications included tramadol, gabapentin, and oxycodone as needed for pain. There were no known adverse reactions to medication. The patient had attended college and worked in an office. She lived with her husband and children. She drank alcohol intermittently and did not use tobacco or other substances. There was no family history of cardiopulmonary or neurologic disorders.
The temperature was 36.6[degrees]C, the heart rate 88 beats per minute, and the blood pressure 118/78 mm Hg while the patient was receiving norepinephrine at a rate of 8 [mu]g per minute. The height was 168 cm and the body-mass index (the weight in kilograms divided by the square of the height in meters) 27.8. The oxygen saturation was 99% while the patient was receiving oxygen through a mechanical ventilator in volume-control mode (tidal volume, 320 ml; positive end-expiratory pressure, 12 cm of water; respiratory rate, 18 breaths per minute; fraction of inspired oxygen, 1.0). The pupils were 2 mm and symmetrically reactive. The lung sounds were coarse. The abdominal incision was well approximated and without drainage; abdominal drains were in place on both sides. A neurologic examination with interruption of sedation showed spontaneous eye-opening but an inability to visually track and to follow commands. Brain-stem reflexes were intact. The legs withdrew equally and briskly in response to pain. The remainder of the examination was normal.
A chest radiograph showed diffuse opacities in both lungs. Levels of electrolytes, urea nitrogen, creatinine, calcium, alanine aminotransferase, bilirubin, creatine kinase, lipase, and ammonia were normal; other laboratory test results are shown in Table 1. Urine human chorionic gonadotropin was undetectable. Urine toxicologic screening was negative except for the presence of opiates. Specimens of blood and urine were obtained for microbiologic culture. An electrocardiogram including posterior leads showed sinus rhythm, rightward axis deviation, diminutive Q waves, and minor nonspecific ST-T-wave abnormalities. An abdominal radiograph showed a nonspecific bowel gas pattern, subcutaneous emphysema, and surgical drains over the pelvis. On bedside cardiac ultrasonography, the left ventricle could not be visualized clearly, but right ventricular dilatation did not appear to be present. Intravenous vancomycin, cefepime, and metronidazole were administered.
Dr. Mendoza: CT of the head, performed without the administration of contrast material, revealed hypodensities in the left basal ganglia and right cerebellum that were suggestive of infarcts; the previously described cerebral edema had reduced slightly. A CT angiogram of the head and neck was normal. CT of the chest, performed after the administration of intravenous contrast material, revealed a reduction in ground-glass opacities but an increase in consolidations, particularly in the lower lobes. CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a small anterior abdominal hematoma and diffuse subcutaneous emphysema.
Dr. Shah: A neurology consultation was obtained; aspirin and atorvastatin were administered. On hospital day 2, the findings on neurologic examination worsened, with only sluggish eye-opening and no motor responses to noxious stimuli. Intravenous mannitol at a dose of 1 g per kilogram of body weight was administered.
Dr. Mendoza: Repeat CT of the head, performed without the administration of contrast material, revealed a hypodensity in the left globus pallidus that had not changed from the previous study, as well as a hypodensity in the right cerebellum that was not definitive and was probably an artifact. Magnetic resonance imaging (MRI) of the head showed infarcts within the globi pallidi and smaller punctate infarcts in the cerebral white matter. There were also innumerable diffuse microhemorrhagic foci affecting the cerebral white matter, including the corpus callosum (Figure 2).	
Figure 2 
Dr. Shah: Bronchoscopy revealed bloody mucus in the distal trachea (Figure 3). Serial bronchoalveolar lavage (BAL) performed in the right upper lobe revealed increasingly erythematous effluent.	
Figure 3
Lupus anticoagulant and anticardiolipin antibodies were not detected. Levels of C3 and C4 were normal. Tests for antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative. Tests for legionella, streptococcus, and galactomannan urinary antigens and antitreponemal antibodies were negative, as was a repeat nucleic acid test for SARS-CoV-2.
Dr. Yasmin Aghajan: On hospital day 3, the patient underwent continuous electroencephalographic monitoring. The study was abnormal because of generalized rhythmic delta activity at a frequency of 1 Hz, which occasionally evolved to generalized periodic discharges superimposed on a disorganized background with irregular delta and theta slowing. There were no epileptiform abnormalities. Although generalized rhythmic delta activity and generalized periodic discharges are on the ictal-interictal continuum, there were no features suggestive of seizures. The electroencephalographic findings were consistent with encephalopathy and the effects of propofol.
A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 26-year-old woman was transferred to this hospital because of respiratory failure and altered mental status.
The patient had been in her usual state of health until 3 days before the current admission, when she underwent elective abdominoplasty and liposuction at an ambulatory surgery center. During the procedure, anesthetic agents included intravenous propofol, fentanyl, midazolam, and ketamine, as well as local lidocaine injections. During recovery after the procedure, medications included intravenous cefazolin, enoxaparin, and ondansetron; oral oxycodone, tramadol, and gabapentin; and transdermal scopolamine. The patient was lethargic after the procedure but was able to be discharged home after a period of observation.
Later that day, the patient was instructed by telephone to take a lower dose of postoperative oxycodone. The next day, on evaluation at the surgical center, she was found to be somnolent but arousable and able to answer questions with effort; the scopolamine patch was removed. Several hours after the patient returned home, her family noticed that she had increased respiratory effort and minimal responsiveness. She was taken by ambulance to the emergency department of a local hospital.
In the emergency department, the temperature was 37.7[degrees]C, the heart rate 130 beats per minute, the blood pressure 121/77 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 83% while the patient was breathing ambient air. She was lethargic, moaned intermittently, and responded with one-word answers; symmetric movement in the arms and legs was observed. Intravenous naloxone was administered, with minor improvement in her condition. Levels of electrolytes and results of kidney- and liver-function tests were normal; other laboratory test results are shown in Table 1. An electrocardiogram showed sinus tachycardia, rightward axis deviation, and nonspecific ST-T-wave changes.	
Table 1 
Dr. Dexter P. Mendoza: A chest radiograph showed diffuse confluent opacities in both lungs (Figure 1A). Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material as part of a pulmonary-embolism protocol, ruled out pulmonary embolism but revealed diffuse mixed ground-glass and consolidative opacities involving all lobes of the lungs, with relative sparing of the subpleural lung (Figure 1B). CT of the abdomen revealed postoperative changes. CT of the head, performed without the administration of contrast material, revealed mild effacement of the cerebral sulci and cisterns on both sides, a finding suggestive of mild diffuse cerebral edema (Figure 1C and 1D). There was also a small hypodensity in the left globus pallidus, a finding suggestive of infarction.	
Figure 1 
Dr. Shah: Noninvasive bilevel positive airway pressure was initiated, and the patient was admitted to the intensive care unit (ICU) at the other hospital. Intravenous vancomycin, piperacillin-tazobactam, levofloxacin, and oseltamivir were administered empirically, and a triple-lumen central venous catheter was inserted.
The next morning, the findings on a repeat chest radiograph appeared to be unchanged, but the patient had progressive lethargy, so intubation was performed and mechanical ventilation was initiated. Pink frothy secretions were noted. Intravenous methylprednisolone, propofol, and norepinephrine were administered. A nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was negative. The troponin I level increased to 4.31 ng per milliliter (reference range, <0.029). The thyrotropin, carboxyhemoglobin, and lipase levels were normal, and tests for Legionella pneumophila and Streptococcus pneumoniae urinary antigens were negative.
Later that afternoon, the patient was transferred to the ICU at this hospital. A review of systems was unavailable because intubation was performed on arrival. Medical history that was obtained from family members included iron-deficiency anemia, anxiety disorder, insomnia, and two normal spontaneous vaginal deliveries. Regular medications included lorazepam as needed for sleep; postoperative medications included tramadol, gabapentin, and oxycodone as needed for pain. There were no known adverse reactions to medication. The patient had attended college and worked in an office. She lived with her husband and children. She drank alcohol intermittently and did not use tobacco or other substances. There was no family history of cardiopulmonary or neurologic disorders.
The temperature was 36.6[degrees]C, the heart rate 88 beats per minute, and the blood pressure 118/78 mm Hg while the patient was receiving norepinephrine at a rate of 8 [mu]g per minute. The height was 168 cm and the body-mass index (the weight in kilograms divided by the square of the height in meters) 27.8. The oxygen saturation was 99% while the patient was receiving oxygen through a mechanical ventilator in volume-control mode (tidal volume, 320 ml; positive end-expiratory pressure, 12 cm of water; respiratory rate, 18 breaths per minute; fraction of inspired oxygen, 1.0). The pupils were 2 mm and symmetrically reactive. The lung sounds were coarse. The abdominal incision was well approximated and without drainage; abdominal drains were in place on both sides. A neurologic examination with interruption of sedation showed spontaneous eye-opening but an inability to visually track and to follow commands. Brain-stem reflexes were intact. The legs withdrew equally and briskly in response to pain. The remainder of the examination was normal.
A chest radiograph showed diffuse opacities in both lungs. Levels of electrolytes, urea nitrogen, creatinine, calcium, alanine aminotransferase, bilirubin, creatine kinase, lipase, and ammonia were normal; other laboratory test results are shown in Table 1. Urine human chorionic gonadotropin was undetectable. Urine toxicologic screening was negative except for the presence of opiates. Specimens of blood and urine were obtained for microbiologic culture. An electrocardiogram including posterior leads showed sinus rhythm, rightward axis deviation, diminutive Q waves, and minor nonspecific ST-T-wave abnormalities. An abdominal radiograph showed a nonspecific bowel gas pattern, subcutaneous emphysema, and surgical drains over the pelvis. On bedside cardiac ultrasonography, the left ventricle could not be visualized clearly, but right ventricular dilatation did not appear to be present. Intravenous vancomycin, cefepime, and metronidazole were administered.
Dr. Mendoza: CT of the head, performed without the administration of contrast material, revealed hypodensities in the left basal ganglia and right cerebellum that were suggestive of infarcts; the previously described cerebral edema had reduced slightly. A CT angiogram of the head and neck was normal. CT of the chest, performed after the administration of intravenous contrast material, revealed a reduction in ground-glass opacities but an increase in consolidations, particularly in the lower lobes. CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a small anterior abdominal hematoma and diffuse subcutaneous emphysema.
Dr. Shah: A neurology consultation was obtained; aspirin and atorvastatin were administered. On hospital day 2, the findings on neurologic examination worsened, with only sluggish eye-opening and no motor responses to noxious stimuli. Intravenous mannitol at a dose of 1 g per kilogram of body weight was administered.
Dr. Mendoza: Repeat CT of the head, performed without the administration of contrast material, revealed a hypodensity in the left globus pallidus that had not changed from the previous study, as well as a hypodensity in the right cerebellum that was not definitive and was probably an artifact. Magnetic resonance imaging (MRI) of the head showed infarcts within the globi pallidi and smaller punctate infarcts in the cerebral white matter. There were also innumerable diffuse microhemorrhagic foci affecting the cerebral white matter, including the corpus callosum (Figure 2).	
Figure 2 
Dr. Shah: Bronchoscopy revealed bloody mucus in the distal trachea (Figure 3). Serial bronchoalveolar lavage (BAL) performed in the right upper lobe revealed increasingly erythematous effluent.	
Figure 3
Lupus anticoagulant and anticardiolipin antibodies were not detected. Levels of C3 and C4 were normal. Tests for antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative. Tests for legionella, streptococcus, and galactomannan urinary antigens and antitreponemal antibodies were negative, as was a repeat nucleic acid test for SARS-CoV-2.
Dr. Yasmin Aghajan: On hospital day 3, the patient underwent continuous electroencephalographic monitoring. The study was abnormal because of generalized rhythmic delta activity at a frequency of 1 Hz, which occasionally evolved to generalized periodic discharges superimposed on a disorganized background with irregular delta and theta slowing. There were no epileptiform abnormalities. Although generalized rhythmic delta activity and generalized periodic discharges are on the ictal-interictal continuum, there were no features suggestive of seizures. The electroencephalographic findings were consistent with encephalopathy and the effects of propofol.
A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with respiratory failure and altered mental status following an elective abdominoplasty and liposuction procedure. She was found to be somnolent and had increased respiratory effort and minimal responsiveness. She was administered several anesthetic agents during the procedure and postoperative medications included opioids and other drugs. Her condition did not improve significantly with naloxone, suggesting that opioid overdose was not the primary issue. Imaging revealed diffuse opacities in the lungs and mild diffuse cerebral edema. The patient's condition worsened with progressive lethargy and she was intubated. Pink frothy secretions were noted, which is a common sign of pulmonary edema. The patient's condition did not improve with antibiotics, suggesting that infection was not the primary issue. The patient's symptoms, the timing of their onset following surgery, and the presence of pink frothy secretions suggest a diagnosis of fat embolism syndrome. Fat embolism syndrome is a rare but serious complication that can occur after procedures such as liposuction. It is caused by fat droplets entering the bloodstream and blocking blood vessels in the lungs, brain, and other organs.\n\nDiagnosis: Fat Embolism Syndrome.""
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        ""content"": ""The patient presented with respiratory failure and altered mental status following an elective abdominoplasty and liposuction procedure. She was found to have diffuse confluent opacities in both lungs and mild diffuse cerebral edema. The patient's condition did not improve with naloxone, suggesting that her symptoms were not solely due to opioid toxicity. The presence of bloody mucus in the distal trachea and increasingly erythematous effluent from bronchoalveolar lavage suggests a pulmonary cause for her symptoms. The patient's symptoms began after surgery, during which she received a number of anesthetic agents including propofol, fentanyl, midazolam, and ketamine, as well as local lidocaine injections. The patient's symptoms, particularly the respiratory failure and altered mental status, are consistent with a severe reaction to one or more of these medications. The patient's symptoms, imaging findings, and the timing of their onset following surgery suggest a diagnosis of acute respiratory distress syndrome (ARDS) and cerebral edema due to anesthetic toxicity.\n\nDiagnosis: Acute respiratory distress syndrome and cerebral edema due to anesthetic toxicity.""
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}", Acute respiratory distress syndrome and cerebral edema due to anesthetic toxicit,N,"{
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        ""content"": ""The patient is a 26-year-old woman who presented with respiratory failure and altered mental status following an elective abdominoplasty and liposuction procedure. She was administered a variety of anesthetic agents and postoperative medications. Her symptoms include lethargy, somnolence, increased respiratory effort, and minimal responsiveness. She also had diffuse confluent opacities in both lungs and mild diffuse cerebral edema. The differential diagnosis for this patient includes drug overdose, pulmonary embolism, pneumonia, and fat embolism syndrome. Drug overdose is less likely as the patient's symptoms did not improve significantly with naloxone administration. Pulmonary embolism was ruled out by a CT scan. Pneumonia is also less likely as the patient's symptoms did not improve with antibiotics and her SARS-CoV-2 test was negative. The patient's symptoms, including respiratory distress, neurological symptoms, and petechial rash, along with her recent surgery, are indicative of fat embolism syndrome. This is further supported by the presence of diffuse microhemorrhagic foci affecting the cerebral white matter, including the corpus callosum, seen on MRI. \n\nDiagnosis: Fat Embolism Syndrome.""
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}",Fat Embolism Syndrome,Y
10.1056/NEJMcpc2107354,"Case 38-2021: A 76-Year-Old Woman with Abdominal Pain, Weight Loss, and Memory Impairment","Hemoglobin (g/dl)   9.4   9.1
Hematocrit (%)   28.3  27.0
Mean corpuscular volume (fl)   89   91.2
Reticulocyte count (%) — — 0.7–2.5 5.7
Platelet count (per μl)   226,000   290,000
White-cell count (per μl)   6900   12,030
Differential count (per μl)
Neutrophils — —   8650
Lymphocytes — —   1940
Monocytes — —   1290
Eosinophils — —   10
Basophils — —  00 20
Immature granulocytes — — 0–100 120
Sodium (mmol/liter)   133   131
Potassium (mmol/liter) 3.5–5.5 3.9   4.1
Chloride (mmol/liter) 99–113 102   99
Carbon dioxide (mmol/liter) 2 1 22   17
Lactic acid (mmol/liter) — —   1.3
Creatinine (mg/dl) 0.5–0.8 0.9   0.97
Urea nitrogen (mg/dl) 9–23 46   42
Calcium (mg/dl) 8.7–10.4 8.9   8.9
Phosphorus (mg/dl) 2.4–5.1 3.0   2.6
Magnesium (mg/dl) 1.6–2.6 3.0   2.4
Alkaline phosphatase (U/liter) 46–116 65   81
Alanine aminotransferase (U/liter) 7–40 47   28
Aspartate aminotransferase (U/liter) 13–40 76   28
Bilirubin (mg/dl)
Total 0.3–1.2 2.5 0–1.0 4.8
Direct 0–0.3 0.9   1.8
International normalized ratio — 1.0 — —
Albumin (g/dl) 3.2–4.8 4.0   4.0
Lactate dehydrogenase (U/liter) 12 46 210 11 10 148
Haptoglobin (mg/dl) — — 3 00 129
Ferritin (μg/liter) — — 1 00 1281
Iron (μg/dl) — — 30–160 157
Total iron-binding capacity (μg/dl) — — 23 4 166
Transferrin saturation (%) — — 14–50 95
Vitamin B12 (pg/ml) — — >231 1277
Folate (ng/ml) — — >4.7 15.3
Glycated hemoglobin (%) — — 4.3–6.4 6.2
Urine
Creatinine, random sample (mg/dl) — — — 100
Osmolality (mOsm/kg water) — — 15 50 787
Sodium (mmol/liter) — — — <20
Urinary porphyrins and porphyrin 
precursors, random sample 
(μg/g creatinine)
Uroporphyrin I 3.6–21.1 26.8 — —
Uroporphyrin III ≤5.6 6.6 — —
Pentacarboxylporphyrins ≤4.1 10.3 — —
Coproporphyrin I 6.5–33.2 191.9 — —
Coproporphyrin III 4.8–88.6 3602.0 — —
Total porphyrins 27. 3.6 3837.6 — —",Lead poisoning,Lead poisoning,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old woman was admitted to this hospital because of abdominal pain, anorexia, weight loss, memory impairment, and suicidal ideation.
The patient had been in her usual state of health until 2 months before this admission, when she began having epigastric pain and anorexia associated with new constipation. Findings on upper and lower endoscopy were reportedly normal, as were the results of serologic testing for celiac disease.
Fifteen days before this admission, the abdominal pain worsened. Ten days before this admission, the patient was admitted to another hospital because of diffuse abdominal pain associated with nausea and poor oral intake. On examination, the patient appeared pale. The abdomen was soft and nontender. The patient was alert and oriented to time, place, and person but had difficulty with word finding. Initial laboratory test results were notable for normocytic anemia and an elevated bilirubin level; other laboratory test results are shown in Table 	
Table 1 
Dr. Ryan Chung: On admission to the other hospital, computed tomography (CT) of the abdomen and pelvis (Figure 1A and 1B) was performed after the administration of intravenous contrast material. There was evidence of a previous cholecystectomy, the common bile duct measured 7 mm in diameter (reference range,   mm after cholecystectomy), and there was mild anasarca with diffuse mesenteric edema. On magnetic resonance cholangiopancreatography (Figure 1C and 1D), the common bile duct again measured 7 mm in diameter; findings were otherwise normal.	
Figure 1 
Dr. Bromberg: After admission to the other hospital, 1 unit of packed red cells was transfused, and the hemoglobin level remained stable thereafter. On the third hospital day, the patient could eat small amounts of food. On further questioning, the patient expressed suicidal ideation and reported a history of prolonged domestic abuse; she was evaluated by the psychiatry service. A diagnosis of post-traumatic stress disorder was made, and lorazepam was administered. The suicidal ideation resolved, but she was noted to need substantial assistance with self-care. While plans were being made for the patient's discharge to an assisted-living facility, the constipation worsened, and her oral intake decreased. On the seventh hospital day, vomiting developed, and the laboratory evaluation was notable for hyponatremia, with a blood sodium level of 120 mmol per liter (reference range, 135 to 145). A nasogastric tube was placed, and 3% hypertonic saline was administered intravenously. On the eighth day at the other hospital, additional imaging studies were obtained.
Dr. Chung: Repeat CT of the abdomen and pelvis (Figure 1E and 1F), performed after the administration of intravenous contrast material, revealed multiple dilated, fluid-filled loops of small bowel that measured up to 4 cm in diameter and the presence of air-fluid levels and an abrupt transition point in the right lower quadrant.
Dr. Bromberg: Urine specimens had been sent for measurement of urinary porphyrin levels at the time of admission to the other hospital; the resulting levels were elevated (Table 1), and the patient was transferred to this hospital for further evaluation.
On admission to this hospital, the patient reported persistent abdominal pain, constipation, and anorexia. The vomiting had resolved after insertion of the nasogastric tube. She reported weight loss of 18 kg over the course of the previous 4 months while she was following a limited diet. In an effort to improve the patient's overall health, the patient's daughter had provided her with supplements and recommended a ketogenic diet consisting of protein and cooked vegetables. The patient also reported that she had been having difficulty with memory for 2 months before this admission.
The patient had a history of type 2 diabetes mellitus, hypertension, and glaucoma. Her surgical history included remote cholecystectomy and hysterectomy. Medications included pantoprazole, ondansetron, and calcium carbonate in combination with cholecalciferol. The patient was allergic to ampicillin, penicillin, trimethoprim-sulfamethoxazole, doxycycline, tetracycline, erythromycin, nitrofurantoin, and nortriptyline - all with unknown reactions. She lived with her sister in suburban New England and reported that she was recently separated from her husband owing to long-standing domestic abuse. The patient had two children. She did not have contact with her son, and her daughter lived in India but visited regularly. Her mother had died from breast cancer. Her father and son both had bipolar affective disorder. The patient did not smoke tobacco, drink alcohol, or use illicit drugs
On examination, the temperature was 36.1[degrees]C, the heart rate 95 beats per minute, the blood pressure 125/55 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 18.5. The patient appeared cachectic. There was a nasogastric tube in place. The conjunctivae were pale. The abdomen was soft and diffusely tender, without guarding, rigidity, or rebound tenderness. There was no rash. The patient was alert but inconsistently oriented to time, place, and person. Her speech was tangential, and she was unable to recite days of the week backward. The remainder of the examination was normal.
The hemoglobin level was 9.1 g per deciliter (reference range, 12.0 to 16.0). Additional laboratory test results are shown in Table 1. A peripheral-blood smear showed normochromic red cells with occasional burr cells and no schistocytes. Reticulocytes, basophilic stippling, and rare nucleated red cells were present; there were no blasts, and the white cells were morphologically normal.
Dr. Chung: Ultrasonography of the right upper quadrant revealed mildly increased echogenicity and mild coarsening of the liver parenchyma (Figure 2). The common bile duct measured 5 mm in diameter.	
Figure 2 
Dr. Bromberg: Intravenous fluids and hemin were administered. On the third hospital day, the volume of output from the nasogastric tube remained elevated. The patient underwent surgical exploration for possible small-bowel obstruction. Dilated loops of small bowel with a transition point near the terminal ileum were observed; there was a loop of small bowel tethered underneath an adhesion band around which the cecum had volvulized. The adhesion was lysed, and the loop of small bowel released. There was no mass or stricture.
A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old woman was admitted to this hospital because of abdominal pain, anorexia, weight loss, memory impairment, and suicidal ideation.
The patient had been in her usual state of health until 2 months before this admission, when she began having epigastric pain and anorexia associated with new constipation. Findings on upper and lower endoscopy were reportedly normal, as were the results of serologic testing for celiac disease.
Fifteen days before this admission, the abdominal pain worsened. Ten days before this admission, the patient was admitted to another hospital because of diffuse abdominal pain associated with nausea and poor oral intake. On examination, the patient appeared pale. The abdomen was soft and nontender. The patient was alert and oriented to time, place, and person but had difficulty with word finding. Initial laboratory test results were notable for normocytic anemia and an elevated bilirubin level; other laboratory test results are shown in Table 	
Table 1 
Dr. Ryan Chung: On admission to the other hospital, computed tomography (CT) of the abdomen and pelvis (Figure 1A and 1B) was performed after the administration of intravenous contrast material. There was evidence of a previous cholecystectomy, the common bile duct measured 7 mm in diameter (reference range,   mm after cholecystectomy), and there was mild anasarca with diffuse mesenteric edema. On magnetic resonance cholangiopancreatography (Figure 1C and 1D), the common bile duct again measured 7 mm in diameter; findings were otherwise normal.	
Figure 1 
Dr. Bromberg: After admission to the other hospital, 1 unit of packed red cells was transfused, and the hemoglobin level remained stable thereafter. On the third hospital day, the patient could eat small amounts of food. On further questioning, the patient expressed suicidal ideation and reported a history of prolonged domestic abuse; she was evaluated by the psychiatry service. A diagnosis of post-traumatic stress disorder was made, and lorazepam was administered. The suicidal ideation resolved, but she was noted to need substantial assistance with self-care. While plans were being made for the patient's discharge to an assisted-living facility, the constipation worsened, and her oral intake decreased. On the seventh hospital day, vomiting developed, and the laboratory evaluation was notable for hyponatremia, with a blood sodium level of 120 mmol per liter (reference range, 135 to 145). A nasogastric tube was placed, and 3% hypertonic saline was administered intravenously. On the eighth day at the other hospital, additional imaging studies were obtained.
Dr. Chung: Repeat CT of the abdomen and pelvis (Figure 1E and 1F), performed after the administration of intravenous contrast material, revealed multiple dilated, fluid-filled loops of small bowel that measured up to 4 cm in diameter and the presence of air-fluid levels and an abrupt transition point in the right lower quadrant.
Dr. Bromberg: Urine specimens had been sent for measurement of urinary porphyrin levels at the time of admission to the other hospital; the resulting levels were elevated (Table 1), and the patient was transferred to this hospital for further evaluation.
On admission to this hospital, the patient reported persistent abdominal pain, constipation, and anorexia. The vomiting had resolved after insertion of the nasogastric tube. She reported weight loss of 18 kg over the course of the previous 4 months while she was following a limited diet. In an effort to improve the patient's overall health, the patient's daughter had provided her with supplements and recommended a ketogenic diet consisting of protein and cooked vegetables. The patient also reported that she had been having difficulty with memory for 2 months before this admission.
The patient had a history of type 2 diabetes mellitus, hypertension, and glaucoma. Her surgical history included remote cholecystectomy and hysterectomy. Medications included pantoprazole, ondansetron, and calcium carbonate in combination with cholecalciferol. The patient was allergic to ampicillin, penicillin, trimethoprim-sulfamethoxazole, doxycycline, tetracycline, erythromycin, nitrofurantoin, and nortriptyline - all with unknown reactions. She lived with her sister in suburban New England and reported that she was recently separated from her husband owing to long-standing domestic abuse. The patient had two children. She did not have contact with her son, and her daughter lived in India but visited regularly. Her mother had died from breast cancer. Her father and son both had bipolar affective disorder. The patient did not smoke tobacco, drink alcohol, or use illicit drugs
On examination, the temperature was 36.1[degrees]C, the heart rate 95 beats per minute, the blood pressure 125/55 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 18.5. The patient appeared cachectic. There was a nasogastric tube in place. The conjunctivae were pale. The abdomen was soft and diffusely tender, without guarding, rigidity, or rebound tenderness. There was no rash. The patient was alert but inconsistently oriented to time, place, and person. Her speech was tangential, and she was unable to recite days of the week backward. The remainder of the examination was normal.
The hemoglobin level was 9.1 g per deciliter (reference range, 12.0 to 16.0). Additional laboratory test results are shown in Table 1. A peripheral-blood smear showed normochromic red cells with occasional burr cells and no schistocytes. Reticulocytes, basophilic stippling, and rare nucleated red cells were present; there were no blasts, and the white cells were morphologically normal.
Dr. Chung: Ultrasonography of the right upper quadrant revealed mildly increased echogenicity and mild coarsening of the liver parenchyma (Figure 2). The common bile duct measured 5 mm in diameter.	
Figure 2 
Dr. Bromberg: Intravenous fluids and hemin were administered. On the third hospital day, the volume of output from the nasogastric tube remained elevated. The patient underwent surgical exploration for possible small-bowel obstruction. Dilated loops of small bowel with a transition point near the terminal ileum were observed; there was a loop of small bowel tethered underneath an adhesion band around which the cecum had volvulized. The adhesion was lysed, and the loop of small bowel released. There was no mass or stricture.
A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Acute Intermittent Porphyria\nThe patient's symptoms of abdominal pain, constipation, and mental status changes, along with her hyponatremia and the finding of elevated urinary porphyrin levels, are suggestive of an acute porphyria. Acute intermittent porphyria is the most common form of acute porphyria, and it often presents with neurovisceral symptoms such as abdominal pain, constipation, and neuropsychiatric symptoms. The patient's hyponatremia can be explained by inappropriate secretion of antidiuretic hormone, which is a common finding in acute porphyria. The patient's symptoms improved with administration of hemin, which is the treatment of choice for acute porphyria attacks.""
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        ""content"": ""The patient's symptoms of abdominal pain, anorexia, weight loss, and memory impairment, along with her lab results showing normocytic anemia and elevated bilirubin level, suggest a systemic issue. The elevated urinary porphyrin levels are indicative of a porphyria, a group of rare genetic disorders that affect the nervous system and skin. The patient's symptoms, particularly the abdominal pain, constipation, and mental changes, are consistent with acute intermittent porphyria, one of the types of porphyria that primarily affects the nervous system. The patient's recent change in diet to a ketogenic diet could have triggered an attack, as fasting and dieting are known triggers for acute intermittent porphyria. The patient's response to treatment with hemin, which is used to treat acute attacks of porphyria, further supports this diagnosis.\n\nDiagnosis: Acute intermittent porphyria.""
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        ""content"": ""The patient is a 76-year-old woman presenting with abdominal pain, anorexia, weight loss, memory impairment, and suicidal ideation. She has a history of type 2 diabetes mellitus, hypertension, and glaucoma. Her symptoms began 2 months prior to admission with epigastric pain and anorexia associated with new constipation. She has had worsening abdominal pain, nausea, and poor oral intake. She has also had difficulty with word finding and has expressed suicidal ideation. She has been diagnosed with post-traumatic stress disorder. She has had a significant weight loss of 18 kg over the past 4 months while following a limited diet. She has also reported memory difficulties for the past 2 months. \n\nThe differential diagnosis for this patient includes gastrointestinal obstruction, malignancy, malnutrition, and porphyria. The patient's CT scan showed evidence of a previous cholecystectomy, the common bile duct measured 7 mm in diameter, and there was mild anasarca with diffuse mesenteric edema. This could suggest a gastrointestinal obstruction. However, the patient's worsening abdominal pain, nausea, and poor oral intake could also suggest a malignancy. The patient's significant weight loss and limited diet could suggest malnutrition. Finally, the patient's memory difficulties and suicidal ideation could suggest a neurological or psychiatric condition such as porphyria.\n\nThe patient's laboratory results showed normocytic anemia and an elevated bilirubin level. Her urine specimens showed elevated urinary porphyrin levels. This is suggestive of porphyria. Porphyria is a group of rare genetic disorders that affect the nervous system and skin. Symptoms can include abdominal pain, constipation, and mental health problems. The patient's symptoms and laboratory results are consistent with this diagnosis.\n\nDiagnosis: Porphyria.""
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10.1056/NEJMcpc2107353,"Case 37-2021: A 60-Year-Old Man with Fevers, Fatigue, Arthralgias, a Mouth Ulcer, and a Rash","Hemoglobin (g/dl)   13.0 — 10.5
Hematocrit (%)   39.1 — 32.4
Mean corpuscular volume (fl)   88.3 — 88.7
White-cell count (per μl)   4900 — 6370
Differential count (per μl)
Neutrophils   3850 — 5180
Immature granulocytes 0–100 70 — 100
Lymphocytes   420 — 520
Eosinophils   70 — 0
Basophils  00 10 — 10
Monocytes   480 — 560
Platelet count (per μl)   169,000 — 243,000
Creatinine (mg/dl)   0.69 — 0.54
Urea nitrogen (mg/dl)   16 — 16
Aspartate aminotransferase (U/liter)   165 — 204
Alanine aminotransferase (U/liter)   165 — 112
Alkaline phosphatase (U/liter)   125 — 232
Total bilirubin (mg/dl)  0.5 — 0.4
Albumin (g/dl)   3.3 — 2.6
Globulin (g/dl)   3.1 — 3.1
Ferritin (μg/liter) 2 00 3089 — —
Creatine kinase (U/liter)   505 906 3220
High-sensitivity troponin T (ng/liter)   15 — —
Lactate dehydrogenase (U/liter) 11 10 386 — —
C-reactive protein (mg/liter)  .0 19.5 — —
Erythrocyte sedimentation rate (mm/hr)  0 29 — —
Thyrotropin (μIU/ml) 0.4 0 0.99 — —
IgG (mg/dl)   — 980 —
IgA (mg/dl)   — 220 —
IgM (mg/dl)   — 50 —
Serum protein electrophoresis — — Normal —
C3 (mg/dl) 81–157 — 91 —
C4 (mg/dl) 12–39 — 40 —
HIV type 1 and 2 antibody and antigen Nonreactive — Nonreactive —
Treponemal antibody Nonreactive — Nonreactive —
Brucella IgG and IgM Negative — Negative —
Coxiella burnetii phase I and II IgG and IgM Negative — Negative —
Coccidioides antibody Negative — Negative —
Cytomegalovirus IgG and DNA, PCR assay Negative — Negative —
Epstein–Barr virus DNA, PCR assay Negative — Negative —
Hepatitis B virus
Surface antibody Negative Negative — —
Surface antigen Negative Negative — —
Core antibody Negative Positive — —
DNA Not detected Not detected — —
Hepatitis C virus antibody Negative Negative — —
Parvovirus B19 DNA Negative — Negative —
Tuberculosis antigen, IGRA Negative — Negative —
Blood cultures Negative Negative Negative —
Babesia, thick and thin smear Negative — Negative —
Lyme disease antibody Negative — Negative —
SARS-CoV-2 IgG and IgM Negative — Negative —
Cryoglobulins None present — None present —
Antinuclear antibody
Qualitative Negative — Positive —
Quantitative — — 1:40–1:160 
(speckled pattern)
—
Antineutrophil cytoplasmic antibody Negative — Negative —
Anti–double-stranded DNA antibody Negative — Negative —
Anti-SSA (Ro) antibody
Qualitative Negative — Positive —
Quantitative (OD units) 0.0–19.0 — 104.04 —
Anti-SSB (La) antibody Negative — Negative —
Anti-Smith antibody Negative — Negative —
Anti–U1-ribonucleoprotein antibody Negative — Negative —
Anti–Scl-70 antibody Negative — Negative —
Anti–Jo-1 antibody Negative — Negative —
Throat swab
Neisseria gonorrhoeae DNA Negative — Negative —
Chlamydia trachomatis DNA Negative — Negative —
Herpes simplex virus type 1 DNA Negative — Negative —
Herpes simplex virus type 2 DNA Negative — Negative —
Swab culture Negative — Negative —
Urine
Histoplasma antigen Negative — Negative —
Blastomyces antigen Negative — Negative —
Urine culture Negative ‚Äö√Ñ√Æ Negative ‚Äö√Ñ√Æ",Anti‚Äö√Ñ√¨melanoma differentiation‚Äö√Ñ√¨associated protein 5 (anti‚Äö√Ñ√¨MDA-5) dermatomyositis,Anti–melanoma differentiation–associated protein 5 (anti–MDA-5) dermatomyositis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 60-year-old man presented to this hospital because of fevers, fatigue, arthralgias, a mouth ulcer, and a rash.
The patient had been in his usual state of health until 1 month before the current presentation, when sore throat, fever, and fatigue developed while he was visiting relatives in the Southwest region of the United States. The symptoms persisted despite regular use of acetaminophen. Two weeks before the current presentation, the patient was evaluated in the emergency department of a local hospital in the Southwest, where a test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reportedly negative. Oral amoxicillin-clavulanic acid and doxycycline were prescribed, and the patient was discharged home.
Ten days before the current presentation, a tongue ulcer developed, along with dry scaly nodules on the face and hands and migratory arthralgias in the wrists, fingers, elbows, and shoulders. Because of worsening symptoms, the patient returned home to Boston by airplane. When he landed in Boston, the patient felt too weak to stand, and an ambulance was called to transport him to this hospital.
In the emergency department, the patient reported ongoing fevers, fatigue, arthralgias, and sore throat. He had lost 4.5 kg over a 1-month period. He had no eye redness or pain, genital ulcers, shortness of breath, cough, nausea, vomiting, diarrhea, or headache. There was no notable medical history, and the patient had not been taking any regular medications before this illness. He had completed a course of oral amoxicillin-clavulanic acid and doxycycline the day before presentation, and he had been taking acetaminophen for the past month. There were no known drug allergies.
The patient was born in China and had immigrated to the United States 20 years earlier. He lived with his wife in Boston. He had not traveled internationally for more than 10 years. The patient had previously worked in environmental maintenance but was retired. He had no history of exposure to animals or fresh water and no sick contacts. He had not been sexually active for several years. He was a smoker with a 30-pack-year history, and he drank alcohol socially; there was no injection-drug use. His family history included colon cancer in his father, lung cancer in his mother, pancreatic cancer in his sister, and hepatocellular carcinoma in his brother.
On examination, the temperature was 37.8[degrees]C, the blood pressure 118/69 mm Hg, the heart rate 78 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The weight was 59 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 19.2. The patient appeared unwell. There was no conjunctival injection. Oral mucous membranes were dry. There was a circular shallow ulcer on the lateral aspect of the tongue on the left side, as well as white plaque on the dorsal aspect of the tongue. There was no cervical, axillary, or inguinal lymphadenopathy. The abdomen was soft and nontender, without hepatosplenomegaly. Strength was 4/5 in both shoulders. The remainder of the neurologic examination was normal. There were several small scaly nodules with a rim of patchy erythema on the fingers, an erosion with serosanguineous crust on the left elbow, and two erythematous and mildly violaceous nodules on the forehead (Fig. 1). There were no genital lesions.	
Figure 1 
Testing of a nasopharyngeal specimen for SARS-CoV-2 RNA was negative. The ferritin level was 3089 [mu]g per liter (reference range, 20 to 300) and the creatine kinase level 505 U per liter (reference range, 60 to 400). Urinalysis showed 2+ ketones and 1+ protein. Additional laboratory test results are shown in Table 1.	
Table 1 
Dr. Karen Rodriguez: Chest radiography performed in the emergency department revealed bibasilar patchy opacities. Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, revealed dependent reticular opacities throughout the lower lobes of the lungs (Fig. 2). CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a left adrenal nodule, measuring 1.2 cm in diameter.	
Figure 2 
Dr. Memel: The patient was admitted to the hospital. Intravenous fluid and oral fluconazole were administered. Biopsies of skin lesions on the left elbow and left side of the forehead were performed. During the next 5 days, the fatigue, arthralgias, skin lesions, and mouth pain continued, and daily fevers with temperatures of up to 38.8[degrees]C were recorded. The mouth lesion did not abate with the use of fluconazole, which was being administered for presumptive oral candidiasis, and the agent was discontinued.
Dr. Samantha N. Champion: Histopathological examination of the biopsy specimen of the forehead lesion revealed vacuolar interface dermatitis with hyperkeratosis, dyskeratosis, pigment incontinence, and sparse perivascular chronic inflammation. Similar findings were observed on histopathological examination of the biopsy specimen of the elbow lesion.
Dr. Memel: Cough developed, and pain in the left shoulder increased. On the fifth hospital day, the creatine kinase level was 906 U per liter. Other laboratory test results are shown in Table 1. The next day, imaging studies of the left shoulder were obtained.
Dr. Rodriguez: Magnetic resonance imaging (MRI) of the left shoulder, performed on hospital day 6, revealed patchy mild intramuscular edema that was most pronounced in the trapezius and deltoid, a finding compatible with myositis (Fig. 2). There was no focal or organized fluid collection.
Dr. Memel: On hospital day 10, biopsy of the left deltoid was performed with the patient under general anesthesia. In the 24 hours after the muscle biopsy, hypoxemia developed, and the patient received 3 liters of supplemental oxygen through a nasal cannula to maintain an oxygen saturation of more than 93%. The next day, the patient received 8 liters of supplemental oxygen through a nasal cannula. Additional laboratory test results are shown in Table 1. Imaging studies of the chest were obtained.
Dr. Rodriguez: Repeat chest radiography revealed progressive patchy opacities at the lung bases. Repeat CT of the chest revealed progressive peribronchovascular and peripheral ground-glass and consolidative opacities predominantly involving the lower lobes, a finding consistent with organizing pneumonia (Fig. 2). In addition, new small left and trace right pleural effusions were present.
Dr. Memel: A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 60-year-old man presented to this hospital because of fevers, fatigue, arthralgias, a mouth ulcer, and a rash.
The patient had been in his usual state of health until 1 month before the current presentation, when sore throat, fever, and fatigue developed while he was visiting relatives in the Southwest region of the United States. The symptoms persisted despite regular use of acetaminophen. Two weeks before the current presentation, the patient was evaluated in the emergency department of a local hospital in the Southwest, where a test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reportedly negative. Oral amoxicillin-clavulanic acid and doxycycline were prescribed, and the patient was discharged home.
Ten days before the current presentation, a tongue ulcer developed, along with dry scaly nodules on the face and hands and migratory arthralgias in the wrists, fingers, elbows, and shoulders. Because of worsening symptoms, the patient returned home to Boston by airplane. When he landed in Boston, the patient felt too weak to stand, and an ambulance was called to transport him to this hospital.
In the emergency department, the patient reported ongoing fevers, fatigue, arthralgias, and sore throat. He had lost 4.5 kg over a 1-month period. He had no eye redness or pain, genital ulcers, shortness of breath, cough, nausea, vomiting, diarrhea, or headache. There was no notable medical history, and the patient had not been taking any regular medications before this illness. He had completed a course of oral amoxicillin-clavulanic acid and doxycycline the day before presentation, and he had been taking acetaminophen for the past month. There were no known drug allergies.
The patient was born in China and had immigrated to the United States 20 years earlier. He lived with his wife in Boston. He had not traveled internationally for more than 10 years. The patient had previously worked in environmental maintenance but was retired. He had no history of exposure to animals or fresh water and no sick contacts. He had not been sexually active for several years. He was a smoker with a 30-pack-year history, and he drank alcohol socially; there was no injection-drug use. His family history included colon cancer in his father, lung cancer in his mother, pancreatic cancer in his sister, and hepatocellular carcinoma in his brother.
On examination, the temperature was 37.8[degrees]C, the blood pressure 118/69 mm Hg, the heart rate 78 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The weight was 59 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 19.2. The patient appeared unwell. There was no conjunctival injection. Oral mucous membranes were dry. There was a circular shallow ulcer on the lateral aspect of the tongue on the left side, as well as white plaque on the dorsal aspect of the tongue. There was no cervical, axillary, or inguinal lymphadenopathy. The abdomen was soft and nontender, without hepatosplenomegaly. Strength was 4/5 in both shoulders. The remainder of the neurologic examination was normal. There were several small scaly nodules with a rim of patchy erythema on the fingers, an erosion with serosanguineous crust on the left elbow, and two erythematous and mildly violaceous nodules on the forehead (Fig. 1). There were no genital lesions.	
Figure 1 
Testing of a nasopharyngeal specimen for SARS-CoV-2 RNA was negative. The ferritin level was 3089 [mu]g per liter (reference range, 20 to 300) and the creatine kinase level 505 U per liter (reference range, 60 to 400). Urinalysis showed 2+ ketones and 1+ protein. Additional laboratory test results are shown in Table 1.	
Table 1 
Dr. Karen Rodriguez: Chest radiography performed in the emergency department revealed bibasilar patchy opacities. Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, revealed dependent reticular opacities throughout the lower lobes of the lungs (Fig. 2). CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a left adrenal nodule, measuring 1.2 cm in diameter.	
Figure 2 
Dr. Memel: The patient was admitted to the hospital. Intravenous fluid and oral fluconazole were administered. Biopsies of skin lesions on the left elbow and left side of the forehead were performed. During the next 5 days, the fatigue, arthralgias, skin lesions, and mouth pain continued, and daily fevers with temperatures of up to 38.8[degrees]C were recorded. The mouth lesion did not abate with the use of fluconazole, which was being administered for presumptive oral candidiasis, and the agent was discontinued.
Dr. Samantha N. Champion: Histopathological examination of the biopsy specimen of the forehead lesion revealed vacuolar interface dermatitis with hyperkeratosis, dyskeratosis, pigment incontinence, and sparse perivascular chronic inflammation. Similar findings were observed on histopathological examination of the biopsy specimen of the elbow lesion.
Dr. Memel: Cough developed, and pain in the left shoulder increased. On the fifth hospital day, the creatine kinase level was 906 U per liter. Other laboratory test results are shown in Table 1. The next day, imaging studies of the left shoulder were obtained.
Dr. Rodriguez: Magnetic resonance imaging (MRI) of the left shoulder, performed on hospital day 6, revealed patchy mild intramuscular edema that was most pronounced in the trapezius and deltoid, a finding compatible with myositis (Fig. 2). There was no focal or organized fluid collection.
Dr. Memel: On hospital day 10, biopsy of the left deltoid was performed with the patient under general anesthesia. In the 24 hours after the muscle biopsy, hypoxemia developed, and the patient received 3 liters of supplemental oxygen through a nasal cannula to maintain an oxygen saturation of more than 93%. The next day, the patient received 8 liters of supplemental oxygen through a nasal cannula. Additional laboratory test results are shown in Table 1. Imaging studies of the chest were obtained.
Dr. Rodriguez: Repeat chest radiography revealed progressive patchy opacities at the lung bases. Repeat CT of the chest revealed progressive peribronchovascular and peripheral ground-glass and consolidative opacities predominantly involving the lower lobes, a finding consistent with organizing pneumonia (Fig. 2). In addition, new small left and trace right pleural effusions were present.
Dr. Memel: A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fever, fatigue, arthralgias, mouth ulcer, and rash, along with his recent travel to the Southwest region of the United States, suggest an infectious disease. The negative test for SARS-CoV-2 rules out COVID-19. The patient's symptoms did not improve with antibiotics, suggesting that the cause may not be bacterial. The presence of a tongue ulcer, dry scaly nodules on the face and hands, and migratory arthralgias are consistent with autoimmune or inflammatory conditions. The patient's elevated ferritin level and creatine kinase level suggest inflammation or tissue damage. The findings of vacuolar interface dermatitis with hyperkeratosis, dyskeratosis, pigment incontinence, and sparse perivascular chronic inflammation in the biopsy specimens are consistent with an autoimmune or inflammatory condition. The MRI findings of patchy mild intramuscular edema in the trapezius and deltoid are consistent with myositis, which can be caused by autoimmune conditions. The progressive patchy opacities at the lung bases and peribronchovascular and peripheral ground-glass and consolidative opacities predominantly involving the lower lobes on chest imaging are consistent with organizing pneumonia, which can be caused by autoimmune conditions. Taken together, these findings suggest an autoimmune or inflammatory condition.\n\nDiagnosis: Autoimmune inflammatory syndrome induced by adjuvants (ASIA)""
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        ""content"": ""The patient's symptoms of fever, fatigue, arthralgias, mouth ulcer, and rash, along with his recent travel to the Southwest region of the United States, suggest an infectious disease. The negative test for SARS-CoV-2 rules out COVID-19. The persistence of symptoms despite antibiotic treatment suggests a non-bacterial infection. The presence of skin lesions and arthralgias could suggest an autoimmune disease, but the lack of response to antibiotics and the patient's recent travel history make an infectious cause more likely. The patient's symptoms, along with the findings of vacuolar interface dermatitis on biopsy, are consistent with a diagnosis of Coccidioidomycosis, a fungal infection endemic to the Southwest United States. This diagnosis is further supported by the patient's lack of response to antibiotics, as Coccidioidomycosis requires antifungal treatment.\n\nDiagnosis: Coccidioidomycosis.""
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        ""content"": ""The patient is a 60-year-old man who presents with fevers, fatigue, arthralgias, a mouth ulcer, and a rash. He also has a history of recent travel to the Southwest region of the United States. The differential diagnosis for this patient includes autoimmune diseases, infectious diseases, and malignancies. Given the patient's age, history of smoking, and family history of various cancers, malignancies should be considered. However, the patient's symptoms are not specific to any particular type of cancer and there is no evidence of a mass or lymphadenopathy on examination. Autoimmune diseases such as lupus or rheumatoid arthritis could also present with similar symptoms, but the patient does not have any known history of autoimmune disease and the presentation is somewhat atypical. Infectious diseases are also a possibility, particularly given the patient's recent travel to the Southwest. Conditions such as coccidioidomycosis (Valley Fever) or histoplasmosis could present with similar symptoms. The patient's symptoms have not improved with antibiotics, suggesting that a bacterial infection is less likely. The patient's skin and muscle biopsy results are suggestive of an inflammatory process, which could be consistent with an infectious or autoimmune etiology. The patient's imaging findings of patchy opacities in the lungs could be consistent with an infectious process such as pneumonia, or possibly a malignancy. However, the patient's symptoms and the progression of his illness are most consistent with an infectious process.\n\nDiagnosis: Coccidioidomycosis (Valley Fever)""
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10.1056/NEJMcpc2107357,Case 36-2021: A 22-Year-Old Man with Pain and Erythema of the Left Hand,"Hemoglobin (g/dl)   14.8
Hematocrit (%)   45.5
White-cell count (per μl)   10,520
Differential count (per μl)
Neutrophils   8650
Immature granulocytes 0–100 30
Lymphocytes   990
Eosinophils   30
Basophils  00 30
Monocytes   790
Platelet count (per μl)   254,000
Sodium (mmol/liter)   139
Potassium (mmol/liter)   3.7
Chloride (mmol/liter)   102
Carbon dioxide (mmol/liter)   23
Creatinine (mg/dl)   0.97
Urea nitrogen (mg/dl)   19
Aspartate aminotransferase (U/liter)   8
Alanine aminotransferase (U/liter)   12
Alkaline phosphatase (U/liter)   40
Total bilirubin (mg/dl)  0.5
International normalized ratio   1.2
Prothrombin time (sec)   15.0
Partial-thromboplastin time (sec) 22. 6.0 31.3
C-reactive protein (mg/liter)  .0 4.1
Erythrocyte sedimentation rate (mm/hr)   2
Lactic acid (mmol/liter)   1.2",Erysipelothrix rhusiopathiae infection.,Cutaneous bacterial infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 22-year-old man was admitted to this hospital because of pain and rapidly spreading erythema of the left hand.
The patient had been well until the day of admission, when he awoke with pain and swelling of the left hand that involved the distal interphalangeal joint of the second finger and the proximal interphalangeal joint of the fourth finger. Over a period of several hours, the pain progressed and bullae began to form. He began to have pain with movement of the second and fourth fingers, and the bullae turned dark purple; these changes prompted the patient to present to the emergency department of this hospital.
In the emergency department, the patient reported pain of the left hand that worsened with movement of the second and fourth fingers. There was no lethargy, fatigue, headache, dyspnea, cough, or pain elsewhere. The patient had no notable medical history and had been well before the day of presentation.
On examination, the patient appeared well. The temperature was 38.6[degrees]C, the blood pressure 126/63 mm Hg, the heart rate 101 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. There were two violaceous, tender bullae on the dorsal aspect of the left hand - one on the distal interphalangeal joint of the second finger and one on the proximal interphalangeal joint of the fourth finger, each measuring 7 mm by 3 mm (Figure 1). In addition, there was nontender, streaking erythema spreading across the dorsal aspect of the left hand, the volar aspect of the left forearm, and the medial aspect of the left upper arm into the axilla. There was no axillary lymphadenopathy.	
Figure 1
On further examination of the left arm, the soft-tissue compartments were soft and compressible, without evidence of crepitus. Finger flexion and extension were intact but limited by pain and swelling in the second and fourth fingers. Results of motor and sensory examinations were normal. The hand was warm. The radial pulse was palpable, and the capillary refill was brisk. The remainder of the overall physical examination was unremarkable. A blood specimen was obtained for culture, a complete blood count, and a metabolic panel. Initial laboratory test results are shown in Table 1.	
Table 1 
Dr. Arvin Kheterpal: Computed tomography (CT) of the left hand and arm, performed after the administration of intravenous contrast material, revealed focal soft-tissue swelling overlying the distal interphalangeal joint of the second finger and the proximal interphalangeal joint of the fourth finger on the dorsal aspect of the left hand (Figure 2). There was no evidence of osseous erosion, periosteal reaction, fracture, joint effusion, fluid collection, or subcutaneous air. The left forearm had a normal appearance on imaging.	
Figure 2
Dr. Winkler: While the patient was in the emergency department, additional history was obtained. The patient was not taking any medications and had no known allergies to medications. He had recently graduated from college and was seeking employment. He lived with his parents in a suburban area of New England. There was no history of recent travel or sick contacts. He rarely drank alcohol and did not smoke cigarettes or use illicit drugs. There was no notable family history.
The patient had recently begun practicing taxidermy as a new hobby. Four days before presentation, he received a frozen deer hide from a friend, which he began to prepare for tanning. When he first received the deer hide, he scraped the skin and fur to remove numerous ticks. On the day before presentation, he kneaded the hide with his hands and massaged into it a mixture of deer brain and tap water that had been prepared the day before and left to stand overnight. While the patient was working with the animal hide, he did not wear protective clothing or gloves. His mother had assisted in part of the process but remained well.
Intravenous fluid, ceftriaxone, and vancomycin were administered, and the patient was admitted to the hospital. Consultants from the orthopedic hand service, dermatology, and infectious diseases evaluated the patient. A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 22-year-old man was admitted to this hospital because of pain and rapidly spreading erythema of the left hand.
The patient had been well until the day of admission, when he awoke with pain and swelling of the left hand that involved the distal interphalangeal joint of the second finger and the proximal interphalangeal joint of the fourth finger. Over a period of several hours, the pain progressed and bullae began to form. He began to have pain with movement of the second and fourth fingers, and the bullae turned dark purple; these changes prompted the patient to present to the emergency department of this hospital.
In the emergency department, the patient reported pain of the left hand that worsened with movement of the second and fourth fingers. There was no lethargy, fatigue, headache, dyspnea, cough, or pain elsewhere. The patient had no notable medical history and had been well before the day of presentation.
On examination, the patient appeared well. The temperature was 38.6[degrees]C, the blood pressure 126/63 mm Hg, the heart rate 101 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. There were two violaceous, tender bullae on the dorsal aspect of the left hand - one on the distal interphalangeal joint of the second finger and one on the proximal interphalangeal joint of the fourth finger, each measuring 7 mm by 3 mm (Figure 1). In addition, there was nontender, streaking erythema spreading across the dorsal aspect of the left hand, the volar aspect of the left forearm, and the medial aspect of the left upper arm into the axilla. There was no axillary lymphadenopathy.	
Figure 1
On further examination of the left arm, the soft-tissue compartments were soft and compressible, without evidence of crepitus. Finger flexion and extension were intact but limited by pain and swelling in the second and fourth fingers. Results of motor and sensory examinations were normal. The hand was warm. The radial pulse was palpable, and the capillary refill was brisk. The remainder of the overall physical examination was unremarkable. A blood specimen was obtained for culture, a complete blood count, and a metabolic panel. Initial laboratory test results are shown in Table 1.	
Table 1 
Dr. Arvin Kheterpal: Computed tomography (CT) of the left hand and arm, performed after the administration of intravenous contrast material, revealed focal soft-tissue swelling overlying the distal interphalangeal joint of the second finger and the proximal interphalangeal joint of the fourth finger on the dorsal aspect of the left hand (Figure 2). There was no evidence of osseous erosion, periosteal reaction, fracture, joint effusion, fluid collection, or subcutaneous air. The left forearm had a normal appearance on imaging.	
Figure 2
Dr. Winkler: While the patient was in the emergency department, additional history was obtained. The patient was not taking any medications and had no known allergies to medications. He had recently graduated from college and was seeking employment. He lived with his parents in a suburban area of New England. There was no history of recent travel or sick contacts. He rarely drank alcohol and did not smoke cigarettes or use illicit drugs. There was no notable family history.
The patient had recently begun practicing taxidermy as a new hobby. Four days before presentation, he received a frozen deer hide from a friend, which he began to prepare for tanning. When he first received the deer hide, he scraped the skin and fur to remove numerous ticks. On the day before presentation, he kneaded the hide with his hands and massaged into it a mixture of deer brain and tap water that had been prepared the day before and left to stand overnight. While the patient was working with the animal hide, he did not wear protective clothing or gloves. His mother had assisted in part of the process but remained well.
Intravenous fluid, ceftriaxone, and vancomycin were administered, and the patient was admitted to the hospital. Consultants from the orthopedic hand service, dermatology, and infectious diseases evaluated the patient. A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with pain, swelling, and rapidly spreading erythema of the left hand, along with the formation of bullae. The symptoms began suddenly and progressed rapidly, which is characteristic of an acute infection. The patient's recent exposure to a deer hide and ticks, along with his manipulation of the hide with bare hands, suggests a zoonotic infection. The patient's symptoms and history are consistent with a diagnosis of cutaneous anthrax, which can be contracted through direct contact with infected animals or animal products. \n\nCutaneous Anthrax""
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        ""content"": ""The patient presents with pain, swelling, and rapidly spreading erythema of the left hand, along with the formation of bullae. These symptoms suggest a severe infection. The patient's recent exposure to a deer hide and ticks, combined with the fact that he did not wear protective clothing or gloves, suggests a zoonotic infection. The rapid progression of symptoms is consistent with a severe bacterial infection. The patient's symptoms and history are consistent with a diagnosis of a severe skin and soft tissue infection caused by a zoonotic pathogen, possibly a tick-borne pathogen.\n\nDiagnosis: Severe skin and soft tissue infection due to a zoonotic pathogen.""
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}", Severe skin and soft tissue infection due to a zoonotic pathogen,Y,"{
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        ""content"": ""The patient is a young man who presents with pain, swelling, and rapidly spreading erythema of the left hand, with bullae formation. These symptoms suggest an infectious process, possibly cellulitis or a more severe skin and soft tissue infection such as necrotizing fasciitis. The patient's recent exposure to a deer hide and ticks could suggest a zoonotic infection such as Lyme disease, but the rapid onset and severity of symptoms are not typical for this condition. The patient's recent manipulation of the deer hide with his bare hands, including the application of a mixture of deer brain and tap water, raises the possibility of a more unusual zoonotic infection. The patient's symptoms and history do not suggest an autoimmune or allergic process. Given the patient's exposure to deer brain, a prion disease could be considered, but these conditions typically present with neurological symptoms, which the patient does not have. The patient's symptoms and history are most consistent with a severe skin and soft tissue infection caused by a zoonotic pathogen, possibly introduced through minor skin abrasions while handling the deer hide.\n\nDiagnosis: Zoonotic skin and soft tissue infection.""
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}",Zoonotic skin and soft tissue infection,Y
10.1056/NEJMcpc2107356,Case 35-2021: A 50-Year-Old Woman with Pain in the Left Upper Quadrant and Hypoxemia,"Hematocrit (%)   35.3
Hemoglobin (g/dl)   11.1
White-cell count (per μl)   16,890
Differential count (per μl)
Neutrophils   8280
Lymphocytes   7430
Monocytes   840
Eosinophils   170
Platelet count (per μl)   183,000
Mean corpuscular volume (fl)   90.3
Prothrombin time (sec)   14.8
Prothrombin-time international 
normalized ratio
  1.2
d-dimer (ng/ml)   2897
Lactate dehydrogenase (U/liter) 11 10 338
C-reactive protein (mg/liter)   94.6",Pneumocystis jirovecii pneumonia,Pneumocystis jirovecii pneumonia,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 50-year-old woman was admitted to this hospital because of pain in the left upper quadrant and hypoxemia.
The patient had been in her usual state of health until 1 year before this admission, when fatigue and weight loss developed and she had abnormal results on liver-function tests after undergoing cholecystectomy for presumed acalculous cholecystitis. Computed tomography (CT) of the abdomen, which was performed as part of the evaluation to determine the cause of the abnormal liver-function test results, revealed hepatosplenomegaly (Figure 1A).	
Figure 1 
Seven months before this admission, a submandibular mass and swelling developed; 1 month later, examination of a biopsy specimen of the mass revealed granulomatous sialadenitis. A liver biopsy was performed to investigate the patient's abdominal distention, poor appetite, and persistently abnormal liver-function test results, which were suggestive of cholestasis. The liver-biopsy specimen showed evidence of granulomatous hepatitis; portal and periportal nonnecrotizing granulomatous inflammation that was associated with multinucleated giant cells, lymphocytes, and some plasma cells; and stage 1 to 2 (portal and periportal) fibrosis. Special stains for organisms (acid-fast and Grocott methenamine-silver stains) were negative.
CT of the chest revealed minimal bibasilar atelectasis and a trace left pleural effusion. An interferon-[gamma] release assay for Mycobacterium tuberculosis was negative. Tests for histoplasma species, blastomyces species, cryptococcus species, coccidioides species, the human immunodeficiency virus (HIV), and hepatitis A, B, and C viruses were all negative, as was testing for antinuclear antibodies, antimitochondrial antibodies, and anti-smooth muscle antibodies. A diagnosis of sarcoidosis was made on the basis of the biopsy results of the submandibular gland and liver and the presence of hypercalcemia and an elevated angiotensin-converting-enzyme level.
Four months before this admission, prednisone therapy was initiated at a dose of 40 mg per day; subsequently, there was a marked reduction in the patient's abdominal distention and marked improvement in her appetite. Liver-function test results also improved. Methotrexate therapy was started at a dose of 15 mg per week, with plans to taper the dose of prednisone.
Three months before this admission, the patient stopped prednisone therapy because of irritability and insomnia. One month later, routine monitoring of the patient's liver function revealed worsening liver-function test results in a cholestatic pattern. This finding was attributed to undertreatment of sarcoidosis, but the patient declined to restart prednisone; the dose of methotrexate was increased to 25 mg per week.
During the next month, the patient noted fatigue, slowly progressive dyspnea on exertion, and cough, without fever or chills. She was evaluated by her primary care physician 1 month before this admission, and a chest radiograph showed bilateral, perihilar, diffuse, symmetric ground-glass opacities with scattered patchy opacities at the lung bases (Figure 1B and 1C). Levofloxacin was administered.
Three weeks before this admission, CT of the abdomen and pelvis revealed worsening hepatosplenomegaly. Prednisone therapy was started at a dose of 20 mg per day.
On the morning of admission, the patient was awakened from sleep by severe, sharp pain in the left upper quadrant. The pain was not worse with eating, and she reported no nausea, vomiting, or diarrhea. Because of persistent pain throughout the day, she presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported progressive dyspnea on exertion and being unable to climb stairs in her home. There was no chest pain, edema in the legs, weight gain, or orthopnea. She had a cough that was productive of clear sputum but had no fevers or chills.
The patient had a history of preeclampsia, Helicobacter pylori infection, cholecystectomy, and papillary thyroid cancer for which she had undergone hemithyroidectomy 9 years before this admission. In addition to methotrexate and prednisone, her medications included omeprazole and trazodone. Her father had hypertension and hyperlipidemia, and one son had ulcerative colitis. Both maternal grandparents had had tuberculosis, but the patient had not had contact with them; her mother had latent tuberculosis. The patient had no known drug allergies. She worked as an administrative assistant and lived with her husband and children in a suburb of Boston. She had never smoked tobacco, did not use illicit drugs, and previously drank one glass of wine per week before her diagnosis of sarcoidosis. She had not traveled outside the United States in the past 5 years.
On examination, the temperature was 36.7[degrees]C, the blood pressure 112/56 mm Hg, the pulse 128 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 85% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 21. The patient was awake and alert but appeared fatigued. The first and second heart sounds (S1 and S2) were normal, without murmurs; the jugular venous pressure, which was measured from the approximate midpoint of the right atrium, was 6 cm of water. Crackles were present in the middle and lower lung fields bilaterally. Normal bowel sounds were present, and the abdomen was soft and nondistended, with tenderness in the left upper quadrant. The liver edge was palpable 3 cm below the right costal margin; the spleen tip was also palpable. There was no edema in the legs. Supplemental oxygen was administered through a nasal cannula at a rate of 3 liters per minute, and the oxygen saturation increased to 93%.
The blood levels of electrolytes, glucose, and lactate were normal, as were the results of kidney-function tests. The level of alanine aminotransferase was 38 IU per liter (reference range, 7 to 33), and the levels of aspartate aminotransferase and total bilirubin were normal. The blood level of alkaline phosphatase was 268 IU per liter (reference range, 30 to 100). Streptococcus pneumoniae and Legionella pneumophila antigens were not detected in the urine. The blood level of 1,3-[beta]-d-glucan was less than 31 pg per milliliter (reference value, <60); other laboratory test results are shown in Table 1.	
Table 1 
Dr. Victorine V. Muse: CT of the abdomen and pelvis (Figure 2A and 2B), performed after the administration of intravenous contrast material, revealed hepatosplenomegaly with a hypodense wedge-shaped region in the midpole of the spleen. A portable anteroposterior chest radiograph (Figure 2C) showed progressive coalescing consolidations in the middle and lower lobes with diffuse ground-glass opacities. CT of the chest (Figure 2D), performed after the administration of intravenous contrast material, revealed new mediastinal and hilar lymphadenopathy and confirmed the presence of multifocal confluent areas of airspace consolidation, with a background of diffuse ground-glass opacities. There was no evidence of pulmonary embolism or pleural effusions.	
Figure 2 
Dr. Shakir: The patient was admitted to the hospital. Treatment with prednisone, methotrexate, and omeprazole was stopped, and trazodone was continued. On hospital day 2, the temperature rose to 39.1[degrees]C, the respiratory rate increased to 32 breaths per minute, and the oxygen saturation decreased to 89% while she was receiving supplemental oxygen through a nasal cannula at a rate of 3 liters per minute. Supplemental oxygen was increased to a rate of 5 liters per minute, and the oxygen saturation increased to 93%. Cultures of the blood were obtained.
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 50-year-old woman was admitted to this hospital because of pain in the left upper quadrant and hypoxemia.
The patient had been in her usual state of health until 1 year before this admission, when fatigue and weight loss developed and she had abnormal results on liver-function tests after undergoing cholecystectomy for presumed acalculous cholecystitis. Computed tomography (CT) of the abdomen, which was performed as part of the evaluation to determine the cause of the abnormal liver-function test results, revealed hepatosplenomegaly (Figure 1A).	
Figure 1 
Seven months before this admission, a submandibular mass and swelling developed; 1 month later, examination of a biopsy specimen of the mass revealed granulomatous sialadenitis. A liver biopsy was performed to investigate the patient's abdominal distention, poor appetite, and persistently abnormal liver-function test results, which were suggestive of cholestasis. The liver-biopsy specimen showed evidence of granulomatous hepatitis; portal and periportal nonnecrotizing granulomatous inflammation that was associated with multinucleated giant cells, lymphocytes, and some plasma cells; and stage 1 to 2 (portal and periportal) fibrosis. Special stains for organisms (acid-fast and Grocott methenamine-silver stains) were negative.
CT of the chest revealed minimal bibasilar atelectasis and a trace left pleural effusion. An interferon-[gamma] release assay for Mycobacterium tuberculosis was negative. Tests for histoplasma species, blastomyces species, cryptococcus species, coccidioides species, the human immunodeficiency virus (HIV), and hepatitis A, B, and C viruses were all negative, as was testing for antinuclear antibodies, antimitochondrial antibodies, and anti-smooth muscle antibodies. A diagnosis of sarcoidosis was made on the basis of the biopsy results of the submandibular gland and liver and the presence of hypercalcemia and an elevated angiotensin-converting-enzyme level.
Four months before this admission, prednisone therapy was initiated at a dose of 40 mg per day; subsequently, there was a marked reduction in the patient's abdominal distention and marked improvement in her appetite. Liver-function test results also improved. Methotrexate therapy was started at a dose of 15 mg per week, with plans to taper the dose of prednisone.
Three months before this admission, the patient stopped prednisone therapy because of irritability and insomnia. One month later, routine monitoring of the patient's liver function revealed worsening liver-function test results in a cholestatic pattern. This finding was attributed to undertreatment of sarcoidosis, but the patient declined to restart prednisone; the dose of methotrexate was increased to 25 mg per week.
During the next month, the patient noted fatigue, slowly progressive dyspnea on exertion, and cough, without fever or chills. She was evaluated by her primary care physician 1 month before this admission, and a chest radiograph showed bilateral, perihilar, diffuse, symmetric ground-glass opacities with scattered patchy opacities at the lung bases (Figure 1B and 1C). Levofloxacin was administered.
Three weeks before this admission, CT of the abdomen and pelvis revealed worsening hepatosplenomegaly. Prednisone therapy was started at a dose of 20 mg per day.
On the morning of admission, the patient was awakened from sleep by severe, sharp pain in the left upper quadrant. The pain was not worse with eating, and she reported no nausea, vomiting, or diarrhea. Because of persistent pain throughout the day, she presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported progressive dyspnea on exertion and being unable to climb stairs in her home. There was no chest pain, edema in the legs, weight gain, or orthopnea. She had a cough that was productive of clear sputum but had no fevers or chills.
The patient had a history of preeclampsia, Helicobacter pylori infection, cholecystectomy, and papillary thyroid cancer for which she had undergone hemithyroidectomy 9 years before this admission. In addition to methotrexate and prednisone, her medications included omeprazole and trazodone. Her father had hypertension and hyperlipidemia, and one son had ulcerative colitis. Both maternal grandparents had had tuberculosis, but the patient had not had contact with them; her mother had latent tuberculosis. The patient had no known drug allergies. She worked as an administrative assistant and lived with her husband and children in a suburb of Boston. She had never smoked tobacco, did not use illicit drugs, and previously drank one glass of wine per week before her diagnosis of sarcoidosis. She had not traveled outside the United States in the past 5 years.
On examination, the temperature was 36.7[degrees]C, the blood pressure 112/56 mm Hg, the pulse 128 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 85% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 21. The patient was awake and alert but appeared fatigued. The first and second heart sounds (S1 and S2) were normal, without murmurs; the jugular venous pressure, which was measured from the approximate midpoint of the right atrium, was 6 cm of water. Crackles were present in the middle and lower lung fields bilaterally. Normal bowel sounds were present, and the abdomen was soft and nondistended, with tenderness in the left upper quadrant. The liver edge was palpable 3 cm below the right costal margin; the spleen tip was also palpable. There was no edema in the legs. Supplemental oxygen was administered through a nasal cannula at a rate of 3 liters per minute, and the oxygen saturation increased to 93%.
The blood levels of electrolytes, glucose, and lactate were normal, as were the results of kidney-function tests. The level of alanine aminotransferase was 38 IU per liter (reference range, 7 to 33), and the levels of aspartate aminotransferase and total bilirubin were normal. The blood level of alkaline phosphatase was 268 IU per liter (reference range, 30 to 100). Streptococcus pneumoniae and Legionella pneumophila antigens were not detected in the urine. The blood level of 1,3-[beta]-d-glucan was less than 31 pg per milliliter (reference value, <60); other laboratory test results are shown in Table 1.	
Table 1 
Dr. Victorine V. Muse: CT of the abdomen and pelvis (Figure 2A and 2B), performed after the administration of intravenous contrast material, revealed hepatosplenomegaly with a hypodense wedge-shaped region in the midpole of the spleen. A portable anteroposterior chest radiograph (Figure 2C) showed progressive coalescing consolidations in the middle and lower lobes with diffuse ground-glass opacities. CT of the chest (Figure 2D), performed after the administration of intravenous contrast material, revealed new mediastinal and hilar lymphadenopathy and confirmed the presence of multifocal confluent areas of airspace consolidation, with a background of diffuse ground-glass opacities. There was no evidence of pulmonary embolism or pleural effusions.	
Figure 2 
Dr. Shakir: The patient was admitted to the hospital. Treatment with prednisone, methotrexate, and omeprazole was stopped, and trazodone was continued. On hospital day 2, the temperature rose to 39.1[degrees]C, the respiratory rate increased to 32 breaths per minute, and the oxygen saturation decreased to 89% while she was receiving supplemental oxygen through a nasal cannula at a rate of 3 liters per minute. Supplemental oxygen was increased to a rate of 5 liters per minute, and the oxygen saturation increased to 93%. Cultures of the blood were obtained.
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Pulmonary Alveolar Proteinosis (PAP) secondary to Sarcoidosis. \n\nThe patient's history of sarcoidosis, along with the presence of hepatosplenomegaly, granulomatous sialadenitis, and granulomatous hepatitis, are consistent with this diagnosis. The patient's worsening respiratory symptoms, including dyspnea on exertion and cough, along with the imaging findings of bilateral, perihilar, diffuse, symmetric ground-glass opacities with scattered patchy opacities at the lung bases, are characteristic of PAP. The patient's hypoxemia and the need for supplemental oxygen further support this diagnosis. PAP is a rare lung disease characterized by the accumulation of surfactant within the alveoli, leading to impaired gas exchange and progressive respiratory failure. It can be primary (idiopathic) or secondary to conditions such as sarcoidosis.""
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        ""content"": ""The patient's history of granulomatous sialadenitis and granulomatous hepatitis, along with hepatosplenomegaly, hypercalcemia, and an elevated angiotensin-converting-enzyme level, led to a diagnosis of sarcoidosis. However, the patient's condition worsened despite treatment with prednisone and methotrexate, and she developed severe, sharp pain in the left upper quadrant, progressive dyspnea on exertion, and cough. CT scans revealed hepatosplenomegaly with a hypodense wedge-shaped region in the midpole of the spleen, new mediastinal and hilar lymphadenopathy, and multifocal confluent areas of airspace consolidation, with a background of diffuse ground-glass opacities. These findings suggest that the patient's sarcoidosis has progressed, leading to splenic infarction and pulmonary sarcoidosis. \n\nDiagnosis: Progressed Sarcoidosis with Splenic Infarction and Pulmonary Sarcoidosis.""
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}",Progressed Sarcoidosis with Splenic Infarction and Pulmonary Sarcoidosis,N,"{
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        ""content"": ""This is a 50-year-old woman with a history of sarcoidosis who presents with left upper quadrant pain and hypoxemia. She has a history of granulomatous sialadenitis and granulomatous hepatitis, and her symptoms improved with prednisone therapy. However, she stopped prednisone due to side effects and her liver function worsened. She then developed progressive dyspnea, cough, and fatigue. Her chest radiograph showed bilateral, perihilar, diffuse, symmetric ground-glass opacities with scattered patchy opacities at the lung bases. She was started on prednisone again due to worsening hepatosplenomegaly. On admission, she had severe left upper quadrant pain and was hypoxemic. \n\nThe differential diagnosis for this patient includes sarcoidosis flare, infection (given her immunosuppressed state), pulmonary embolism, and malignancy. Given her history of sarcoidosis and the fact that her symptoms improved with prednisone, a flare of her sarcoidosis is likely. However, her immunosuppressed state makes her susceptible to infections, which could also explain her symptoms. Her dyspnea and hypoxemia could be due to a pulmonary embolism, although her CT scan did not show any evidence of this. Finally, malignancy could also present with her symptoms, although this is less likely given her history and presentation.\n\nGiven her history of sarcoidosis, the improvement of her symptoms with prednisone, and the worsening of her symptoms after stopping prednisone, the most likely diagnosis is a flare of her sarcoidosis. \n\nDiagnosis: Sarcoidosis flare.""
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10.1056/NEJMcpc2107352,Case 33-2021: A 68-Year-Old Man with Painful Mouth Ulcers,"Hemoglobin (g/dl)   14.4 13.6 14.5 13.1
Hematocrit (%)   43.8 39.8 43.0 39.4
Mean corpuscular volume (fl)   95.2 94.8 92.5 93.4
White-cell count (per μl)   8150 8690 15,830 9510
Differential count (per μl)
Neutrophils   4560 4440 10,290 5250
Immature granulocytes 0–100 140 170 790 —
Lymphocytes   1410 1490 1380 1400
Eosinophils   1100 1200 690 1400
Basophils  00 70 70 190 —
Monocytes   870 1320 2490 1470
Platelet count (per μl)   255,000 235,000 301,000 172,000
C-reactive protein (mg/liter)  .0 10.6 21.5 — —
Erythrocyte sedimentation rate (mm/hr)  0 13 16 — —
Ferritin (μg/liter) 2 00 — 338 — —
Vitamin B12 (pg/ml) >231 — >2000 — —
Folate (ng/ml) >4.7 — 14.7 — —
Cytomegalovirus
DNA, PCR assay Not detected — Not detected — —
IgG — — Negative — —
IgM — — Negative — —
Epstein–Barr virus
DNA, PCR assay Not detected — Not detected — —
IgG — — Positive — —
IgM — — Negative — —
Coxsackievirus antibody <1:8 — <1:8 — —
Antinuclear antibody — — Positive (1:320; 
homogeneous 
pattern)
— —
Antineutrophil cytoplasmic antibody Negative — Negative — —
Double-stranded DNA antibody Negative at 1:10 — Negative at 1:10 — —
Anti-SSA (Ro) antibody Negative — Negative — —
Anti-SSB (La) antibody Negative — Negative — —
Anti-Smith antibody Negative — Negative — —
Anti–U1-ribonucleoprotein antibody Negative — Negative — —
Histoplasma antibody, serum Negative — — — Negative
Lyme disease antibody Negative — — — Negative
SARS-CoV-2, PCR assay Negative — — — Negative
Bullous pemphigoid 180 IgG (RU/ml) <20 — — — 57
Bullous pemphigoid 230 IgG (RU/ml) <20 — — — 43
Desmoglein 1 antibody (RU/ml) <20 — — — <2
Desmoglein 3 antibody (RU/ml) <20 — — — 15",Eosinophilic leukemia,"Leukemia, perhaps of eosinophilic lineage.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old man was admitted to this hospital because of painful mouth ulcers and weight loss.
The patient had been well until 6 weeks before the current admission, when painful mouth ulcers and neck pain developed. He was evaluated at an urgent care center. He had reduced range of motion of the neck due to pain with flexion, extension, and rotation, but there was no spinal tenderness. There were small ulcers on the lower lip and gingivae. Cyclobenzaprine and acyclovir were prescribed.
Five weeks before the current admission, the patient was evaluated by his primary care physician in a clinic at this hospital. He reported that neck pain on the right side and oral ulcers had persisted and that several new oral ulcers had developed. He had no rash, eye pain, joint pain or swelling, dysuria or genital lesions, abdominal pain, or diarrhea. The examination was notable for several large ulcers on the lips and tongue (Figure 1A). Treatment with acyclovir was continued. A direct immunofluorescence assay of a swab of an oral ulcer was negative for herpes simplex virus (HSV) types 1 and 2 and for varicella-zoster virus. Blood tests were negative for human immunodeficiency virus (HIV) types 1 and 2 and for syphilis; other laboratory test results are shown in Table 1. The patient was referred to the dermatology clinic for further evaluation of the oral ulcers.	
Figure 1 
Before the patient could be evaluated in the dermatology clinic, his mouth ulcers and pain worsened. Four weeks before the current admission, he presented to the emergency department of this hospital. Erythema and watering of the left eye had developed, as had new skin lesions on the trunk and upper face. The examination revealed multiple ulcers on the lips and tongue (Figure 1B) and two pink crusted papules with hemorrhage on the right temple. There were scattered pustules on the lower back and right flank. An ophthalmologic examination revealed a pinguecula on the nasal side of the right eye with mild surrounding inflammation but was otherwise normal. Blood levels of electrolytes and glucose were normal, as were results of kidney- and liver-function tests. HLA typing was positive for the HLA-B51 allele; other laboratory test results are shown in Table 1.
The patient was evaluated by the rheumatology and dermatology services. The decision was made to pursue a skin biopsy before an oral biopsy. A biopsy of a pustule on the patient's back was performed, and examination of the specimen revealed mild spongiosis, neutrophilic granulomatous inflammation, and a superficial perivascular lymphohistiocytic infiltrate with neutrophils and occasional eosinophils. Colchicine was prescribed, along with oxycodone and lidocaine oral solution, for the treatment of a working diagnosis of Behcet's disease. Outpatient follow-up with the rheumatology service was arranged.
Three days after discharge from the emergency department, the patient reported that the oral ulcers had not abated. Treatment with prednisone was started, and colchicine was continued.
Two weeks before the current admission, the patient was evaluated in the rheumatology clinic of this hospital. Prednisone treatment had led to only transient healing of the oral ulcers. The patient had pain with eating and speaking and had lost 10 kg of body weight in 3 weeks. The neck pain, the eye watering, and several skin lesions had resolved. The examination revealed extensive ulceration of the upper and lower labial mucosa and of the ventrolateral surface of the tongue on both sides, as well as two focal ulcerations, measuring 0.5 cm in diameter, involving the soft palate on the left side (Figure 1C and 1D). There were multiple purple-red, scaly papules involving the skin of the arms and lower legs. There was no evidence of a joint abnormality. Laboratory test results are shown in Table 1. Prednisone was switched to oral methylprednisolone, and treatment with amoxicillin-clavulanate was started for possible bowel-associated dermatosis-arthritis syndrome. Omeprazole, which the patient had taken for many years, was stopped because of peripheral eosinophilia. An evaluation in the oral medicine clinic at an affiliated hospital was arranged, with plans for oral and skin biopsies.
One week before the current admission, a biopsy of lower labial mucosa revealed squamous mucosa and parenchyma of the minor salivary glands, with mild nonspecific chronic inflammation. A skin biopsy was notable for epidermal ulceration with impetiginization and associated folliculitis. Dexamethasone oral rinses were prescribed, as was trimethoprim-sulfamethoxazole for prophylaxis against Pneumocystis jiroveci infection.
During the next 7 days, the ulcers worsened and the patient had ongoing pain that was unresponsive to oxycodone. He was unable to eat and was admitted to this hospital for pain control and further evaluation.
The patient's medical history included gastroesophageal reflux disease. Medications included methylprednisolone, colchicine, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, lorazepam, and oxycodone, as well as dexamethasone oral rinses. The patient was allergic to clarithromycin, which had caused a rash. He had quit smoking 30 years earlier, and he consumed 10 alcoholic drinks per week. There was no illicit drug use. The patient lived with his wife in a suburban area of New England. He had traveled to Western Europe, Mexico, and the Caribbean. He was employed part-time as a contractor. His family history included prostate cancer in his father and type 2 diabetes mellitus in his mother.
On examination, the temperature was 35.8[degrees]C, the blood pressure 134/56 mm Hg, the heart rate 70 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 26.4. The patient looked uncomfortable, with an edematous tongue and multiple oral ulcers. There was no cervical lymphadenopathy or joint abnormality. Skin examination revealed a slightly raised pustule, measuring 2 mm in diameter, on the anterior aspect of the thigh. The remainder of the examination was normal. Laboratory test results are shown in Table 1.
Dr. Markus Y. Wu: Computed tomography (CT) of chest and abdomen, performed after the administration of intravenous contrast material, revealed subtle centrilobular ground-glass opacities in the upper lobes of the lungs, as well as prominent right hilar and left supraclavicular lymph nodes, each measuring 1 cm in diameter (Figure 2).	
Figure 2 
Dr. Cooley: A diagnostic procedure was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old man was admitted to this hospital because of painful mouth ulcers and weight loss.
The patient had been well until 6 weeks before the current admission, when painful mouth ulcers and neck pain developed. He was evaluated at an urgent care center. He had reduced range of motion of the neck due to pain with flexion, extension, and rotation, but there was no spinal tenderness. There were small ulcers on the lower lip and gingivae. Cyclobenzaprine and acyclovir were prescribed.
Five weeks before the current admission, the patient was evaluated by his primary care physician in a clinic at this hospital. He reported that neck pain on the right side and oral ulcers had persisted and that several new oral ulcers had developed. He had no rash, eye pain, joint pain or swelling, dysuria or genital lesions, abdominal pain, or diarrhea. The examination was notable for several large ulcers on the lips and tongue (Figure 1A). Treatment with acyclovir was continued. A direct immunofluorescence assay of a swab of an oral ulcer was negative for herpes simplex virus (HSV) types 1 and 2 and for varicella-zoster virus. Blood tests were negative for human immunodeficiency virus (HIV) types 1 and 2 and for syphilis; other laboratory test results are shown in Table 1. The patient was referred to the dermatology clinic for further evaluation of the oral ulcers.	
Figure 1 
Before the patient could be evaluated in the dermatology clinic, his mouth ulcers and pain worsened. Four weeks before the current admission, he presented to the emergency department of this hospital. Erythema and watering of the left eye had developed, as had new skin lesions on the trunk and upper face. The examination revealed multiple ulcers on the lips and tongue (Figure 1B) and two pink crusted papules with hemorrhage on the right temple. There were scattered pustules on the lower back and right flank. An ophthalmologic examination revealed a pinguecula on the nasal side of the right eye with mild surrounding inflammation but was otherwise normal. Blood levels of electrolytes and glucose were normal, as were results of kidney- and liver-function tests. HLA typing was positive for the HLA-B51 allele; other laboratory test results are shown in Table 1.
The patient was evaluated by the rheumatology and dermatology services. The decision was made to pursue a skin biopsy before an oral biopsy. A biopsy of a pustule on the patient's back was performed, and examination of the specimen revealed mild spongiosis, neutrophilic granulomatous inflammation, and a superficial perivascular lymphohistiocytic infiltrate with neutrophils and occasional eosinophils. Colchicine was prescribed, along with oxycodone and lidocaine oral solution, for the treatment of a working diagnosis of Behcet's disease. Outpatient follow-up with the rheumatology service was arranged.
Three days after discharge from the emergency department, the patient reported that the oral ulcers had not abated. Treatment with prednisone was started, and colchicine was continued.
Two weeks before the current admission, the patient was evaluated in the rheumatology clinic of this hospital. Prednisone treatment had led to only transient healing of the oral ulcers. The patient had pain with eating and speaking and had lost 10 kg of body weight in 3 weeks. The neck pain, the eye watering, and several skin lesions had resolved. The examination revealed extensive ulceration of the upper and lower labial mucosa and of the ventrolateral surface of the tongue on both sides, as well as two focal ulcerations, measuring 0.5 cm in diameter, involving the soft palate on the left side (Figure 1C and 1D). There were multiple purple-red, scaly papules involving the skin of the arms and lower legs. There was no evidence of a joint abnormality. Laboratory test results are shown in Table 1. Prednisone was switched to oral methylprednisolone, and treatment with amoxicillin-clavulanate was started for possible bowel-associated dermatosis-arthritis syndrome. Omeprazole, which the patient had taken for many years, was stopped because of peripheral eosinophilia. An evaluation in the oral medicine clinic at an affiliated hospital was arranged, with plans for oral and skin biopsies.
One week before the current admission, a biopsy of lower labial mucosa revealed squamous mucosa and parenchyma of the minor salivary glands, with mild nonspecific chronic inflammation. A skin biopsy was notable for epidermal ulceration with impetiginization and associated folliculitis. Dexamethasone oral rinses were prescribed, as was trimethoprim-sulfamethoxazole for prophylaxis against Pneumocystis jiroveci infection.
During the next 7 days, the ulcers worsened and the patient had ongoing pain that was unresponsive to oxycodone. He was unable to eat and was admitted to this hospital for pain control and further evaluation.
The patient's medical history included gastroesophageal reflux disease. Medications included methylprednisolone, colchicine, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, lorazepam, and oxycodone, as well as dexamethasone oral rinses. The patient was allergic to clarithromycin, which had caused a rash. He had quit smoking 30 years earlier, and he consumed 10 alcoholic drinks per week. There was no illicit drug use. The patient lived with his wife in a suburban area of New England. He had traveled to Western Europe, Mexico, and the Caribbean. He was employed part-time as a contractor. His family history included prostate cancer in his father and type 2 diabetes mellitus in his mother.
On examination, the temperature was 35.8[degrees]C, the blood pressure 134/56 mm Hg, the heart rate 70 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 26.4. The patient looked uncomfortable, with an edematous tongue and multiple oral ulcers. There was no cervical lymphadenopathy or joint abnormality. Skin examination revealed a slightly raised pustule, measuring 2 mm in diameter, on the anterior aspect of the thigh. The remainder of the examination was normal. Laboratory test results are shown in Table 1.
Dr. Markus Y. Wu: Computed tomography (CT) of chest and abdomen, performed after the administration of intravenous contrast material, revealed subtle centrilobular ground-glass opacities in the upper lobes of the lungs, as well as prominent right hilar and left supraclavicular lymph nodes, each measuring 1 cm in diameter (Figure 2).	
Figure 2 
Dr. Cooley: A diagnostic procedure was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of painful mouth ulcers, neck pain, and weight loss, along with the development of new skin lesions and eye inflammation, initially suggested Behcet's disease. However, the patient's condition did not improve with treatment for Behcet's disease, and a biopsy of the oral ulcers revealed nonspecific chronic inflammation. The presence of centrilobular ground-glass opacities in the upper lobes of the lungs and prominent lymph nodes in the right hilar and left supraclavicular regions, as revealed by a CT scan, suggest a systemic disease. Given the patient's age, the presence of these symptoms, and the lack of improvement with treatment for Behcet's disease, a diagnosis of lymphoma should be considered. \n\nDiagnosis: Lymphoma""
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        ""content"": ""The patient's symptoms include painful mouth ulcers, neck pain, weight loss, and skin lesions. The patient was initially treated for a possible herpes simplex virus infection, but testing for HSV was negative. The patient was also tested for HIV and syphilis, both of which were negative. The patient's symptoms did not improve with acyclovir treatment, suggesting that the cause is not viral. The patient was then treated with colchicine and prednisone for a possible diagnosis of Behcet's disease, but the symptoms did not improve significantly. A biopsy of the patient's skin revealed neutrophilic granulomatous inflammation, which is not typically associated with Behcet's disease. The patient's HLA-B51 allele was positive, which is associated with Behcet's disease, but the lack of improvement with treatment and the biopsy results suggest a different diagnosis. The patient's symptoms and the biopsy results are consistent with a diagnosis of neutrophilic dermatosis, specifically Sweet's syndrome. \n\nDiagnosis: Sweet's Syndrome""
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        ""content"": ""The patient is a 68-year-old man presenting with painful mouth ulcers and weight loss. The differential diagnosis for this patient includes Behcet's disease, herpes simplex virus (HSV) infection, autoimmune blistering diseases (such as pemphigus vulgaris), and malignancy (such as oral squamous cell carcinoma). The patient's negative HSV test and lack of response to acyclovir make HSV infection unlikely. The patient's lack of response to prednisone and colchicine, as well as the absence of genital ulcers, eye inflammation, or joint abnormalities, make Behcet's disease less likely. The patient's skin biopsy did not show the acantholysis typical of pemphigus vulgaris, making this diagnosis less likely. The patient's age, history of smoking, and lack of response to immunosuppressive therapy raise concern for malignancy. The patient's CT scan showed prominent hilar and supraclavicular lymph nodes, which could be indicative of metastatic disease. The patient's oral biopsy showed chronic inflammation, but no malignancy was mentioned. However, given the patient's clinical presentation and lack of response to therapy, a repeat biopsy or a biopsy of a different site may be warranted to rule out malignancy.\n\nDiagnosis: Oral squamous cell carcinoma (pending further biopsy confirmation).""
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10.1056/NEJMcpc2107351,Case 32-2021: A 14-Year-Old Girl with Swelling of the Jaw and Hypercalcemia,,Primary hyperparathyroidism and brown tumor,Primary hyperparathyroidism and brown tumor,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 14-year-old girl was admitted to this hospital because of swelling of the left jaw.
The patient had been well until 6 weeks before this admission, when she noticed a lump in the left lower jaw; there was no pain, tenderness, or discomfort in the jaw. She was evaluated in a primary care clinic of another hospital and was told that a salivary gland may be obstructed. Treatment with sialagogues, increased oral hydration, warm compresses, and massage of the salivary glands were recommended. During the next 3 weeks, the lump in the left jaw increased in size, and swelling of the left side of the face and neck developed. Three weeks before this admission, she returned to the primary care clinic; treatment with cephalexin was started.
Eighteen days before this admission, the patient was evaluated in the otolaryngology clinic of the other hospital. The temperature was 37.2[degrees]C, the blood pressure 132/90 mm Hg, the heart rate 86 beats per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.0. There was swelling in the left mandibular and submandibular areas, with no erythema, fluctuance, or palpable salivary stones.
Dr. Hillary R. Kelly: Computed tomography (CT) of the face and neck was performed after the administration of intravenous contrast material. CT of the face (Figure 1) revealed a 3.7-cm mass in the left mandibular body, with lytic and expansile features and numerous internal wavy septations. Areas of marked thinning and obliteration were noted in the buccal and lingual cortexes of the mandible, and extension of the mass among the roots of the first molar, second molar, and premolar was observed. No fluid-fluid or blood-fluid levels were seen within the lesion. There was no lymphadenopathy. The patient was referred to the otolaryngology clinic at this hospital.	
Figure 1
Dr. Be: Fifteen days before this admission, the patient reported numbness and tingling in the lower lip and chin on the left side. She had had no fatigue, fever, chills, or redness and no pain in her face, jaw, or neck. On examination, she appeared well but had obvious facial asymmetry with swelling of the left mandible (Figure 2). There was a firm, mildly tender mass in the body of the left mandible that extended to the mandibular angle. Orthodontic braces were in place and dentition and jaw occlusion were normal. The remainder of the ear, nose, and throat examination was normal. The overlying skin was normal, and no anterior or posterior submandibular or supraclavicular lymphadenopathy was present. The blood levels of sodium, potassium, and chloride were normal, as were the complete blood count and the results of tests of coagulation and renal function. The calcium level was 11.8 mg per deciliter (3.0 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter [2.1 to 2.6 mmol per liter]), and the albumin level was 4.1 g per deciliter (reference range, 3.3 to 5.0). Radiography of the chest was normal.	
Figure 2 
Dr. Vania Nose: An intraoral biopsy of the left mandibular mass was performed. Pathological examination (Figure 3C) of the biopsy specimen revealed that the lesion was partially surrounded by reactive bone trabeculae, was hemorrhagic, and contained numerous osteoclast-type giant cells around extravasated red cells, findings that were consistent with a central giant-cell lesion or a central giant-cell granuloma.	
Figure 3
Dr. Be: Ten days before this admission, the patient was seen in the oral and maxillofacial surgical clinic of this hospital, and admission for the excision of the left mandibular mass was planned.
On admission to this hospital, additional history was obtained. The patient had normal growth and development and had reportedly received all routine childhood vaccinations. She had finished the prescribed course of cephalexin and had taken no other medications; penicillin had caused fever and hives early in childhood. She lived in a suburban area of New England with her mother, stepfather, and two cats; she frequently stayed in another suburban area of New England with her father. The patient performed well in high school and participated in theater. She did not smoke tobacco, use illicit drugs, or drink alcohol. Her mother had hypothyroidism; her father had obstructive sleep apnea. Her maternal grandmother had a history of hypothyroidism, parathyroid adenoma, breast cancer, and colon cancer; her paternal grandfather had died from colon cancer.
The temperature was 36.6[degrees]C, the blood pressure 128/85 mm Hg, and the heart rate 111 beats per minute. The physical examination was unchanged. The left mandibular mass was excised. Pathological examination of the surgical specimen revealed abundant giant cells.
On the second hospital day, the calcium level was 12.6 mg per deciliter (3.2 mmol per liter) and the parathyroid hormone (PTH) level was 396 pg per milliliter (reference range, 10 to 60).
A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 14-year-old girl was admitted to this hospital because of swelling of the left jaw.
The patient had been well until 6 weeks before this admission, when she noticed a lump in the left lower jaw; there was no pain, tenderness, or discomfort in the jaw. She was evaluated in a primary care clinic of another hospital and was told that a salivary gland may be obstructed. Treatment with sialagogues, increased oral hydration, warm compresses, and massage of the salivary glands were recommended. During the next 3 weeks, the lump in the left jaw increased in size, and swelling of the left side of the face and neck developed. Three weeks before this admission, she returned to the primary care clinic; treatment with cephalexin was started.
Eighteen days before this admission, the patient was evaluated in the otolaryngology clinic of the other hospital. The temperature was 37.2[degrees]C, the blood pressure 132/90 mm Hg, the heart rate 86 beats per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.0. There was swelling in the left mandibular and submandibular areas, with no erythema, fluctuance, or palpable salivary stones.
Dr. Hillary R. Kelly: Computed tomography (CT) of the face and neck was performed after the administration of intravenous contrast material. CT of the face (Figure 1) revealed a 3.7-cm mass in the left mandibular body, with lytic and expansile features and numerous internal wavy septations. Areas of marked thinning and obliteration were noted in the buccal and lingual cortexes of the mandible, and extension of the mass among the roots of the first molar, second molar, and premolar was observed. No fluid-fluid or blood-fluid levels were seen within the lesion. There was no lymphadenopathy. The patient was referred to the otolaryngology clinic at this hospital.	
Figure 1
Dr. Be: Fifteen days before this admission, the patient reported numbness and tingling in the lower lip and chin on the left side. She had had no fatigue, fever, chills, or redness and no pain in her face, jaw, or neck. On examination, she appeared well but had obvious facial asymmetry with swelling of the left mandible (Figure 2). There was a firm, mildly tender mass in the body of the left mandible that extended to the mandibular angle. Orthodontic braces were in place and dentition and jaw occlusion were normal. The remainder of the ear, nose, and throat examination was normal. The overlying skin was normal, and no anterior or posterior submandibular or supraclavicular lymphadenopathy was present. The blood levels of sodium, potassium, and chloride were normal, as were the complete blood count and the results of tests of coagulation and renal function. The calcium level was 11.8 mg per deciliter (3.0 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter [2.1 to 2.6 mmol per liter]), and the albumin level was 4.1 g per deciliter (reference range, 3.3 to 5.0). Radiography of the chest was normal.	
Figure 2 
Dr. Vania Nose: An intraoral biopsy of the left mandibular mass was performed. Pathological examination (Figure 3C) of the biopsy specimen revealed that the lesion was partially surrounded by reactive bone trabeculae, was hemorrhagic, and contained numerous osteoclast-type giant cells around extravasated red cells, findings that were consistent with a central giant-cell lesion or a central giant-cell granuloma.	
Figure 3
Dr. Be: Ten days before this admission, the patient was seen in the oral and maxillofacial surgical clinic of this hospital, and admission for the excision of the left mandibular mass was planned.
On admission to this hospital, additional history was obtained. The patient had normal growth and development and had reportedly received all routine childhood vaccinations. She had finished the prescribed course of cephalexin and had taken no other medications; penicillin had caused fever and hives early in childhood. She lived in a suburban area of New England with her mother, stepfather, and two cats; she frequently stayed in another suburban area of New England with her father. The patient performed well in high school and participated in theater. She did not smoke tobacco, use illicit drugs, or drink alcohol. Her mother had hypothyroidism; her father had obstructive sleep apnea. Her maternal grandmother had a history of hypothyroidism, parathyroid adenoma, breast cancer, and colon cancer; her paternal grandfather had died from colon cancer.
The temperature was 36.6[degrees]C, the blood pressure 128/85 mm Hg, and the heart rate 111 beats per minute. The physical examination was unchanged. The left mandibular mass was excised. Pathological examination of the surgical specimen revealed abundant giant cells.
On the second hospital day, the calcium level was 12.6 mg per deciliter (3.2 mmol per liter) and the parathyroid hormone (PTH) level was 396 pg per milliliter (reference range, 10 to 60).
A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with a mass in the left mandibular body, with lytic and expansile features and numerous internal wavy septations. The mass is associated with numbness and tingling in the lower lip and chin on the left side. Pathological examination of the biopsy specimen revealed that the lesion was partially surrounded by reactive bone trabeculae, was hemorrhagic, and contained numerous osteoclast-type giant cells around extravasated red cells, findings that were consistent with a central giant-cell lesion or a central giant-cell granuloma. However, the elevated calcium and parathyroid hormone (PTH) levels suggest a parathyroid-related issue. Given the patient's age and the location of the mass, the most likely diagnosis is a parathyroid adenoma or hyperplasia, which can cause hypercalcemia and bone changes. \n\nDiagnosis: Parathyroid adenoma or hyperplasia.""
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        ""content"": ""The patient is a 14-year-old girl presenting with a swelling of the left jaw, which was initially thought to be an obstructed salivary gland. However, the swelling increased in size and the patient reported numbness and tingling in the lower lip and chin on the left side. A CT scan revealed a 3.7-cm mass in the left mandibular body with lytic and expansile features and numerous internal wavy septations. The patient's calcium level was elevated, and a biopsy of the mass revealed numerous osteoclast-type giant cells, consistent with a central giant-cell lesion or a central giant-cell granuloma. The patient's parathyroid hormone (PTH) level was also significantly elevated. \n\nThe differential diagnosis for this patient includes central giant cell granuloma, brown tumor of hyperparathyroidism, and other benign or malignant tumors of the jaw. Central giant cell granuloma is a benign condition that typically presents in young patients and can cause bone expansion and facial asymmetry, but it would not explain the elevated calcium and PTH levels. Brown tumor of hyperparathyroidism is a rare manifestation of hyperparathyroidism that can present with similar symptoms and histological findings, and it would explain the elevated calcium and PTH levels. Other benign or malignant tumors of the jaw are less likely given the patient's age, the specific histological findings, and the elevated calcium and PTH levels.\n\nGiven the patient's presentation, the histological findings, and the elevated calcium and PTH levels, the most likely diagnosis is a brown tumor of hyperparathyroidism. \n\nDiagnosis: Brown tumor of hyperparathyroidism.""
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10.1056/NEJMcpc2027096,"Case 31-2021: A 21-Year-Old Man with Sore Throat, Epistaxis, and Oropharyngeal Petechiae","Hemoglobin (g/dl)   9.8   10.0 8.4
Hematocrit (%)   29.4   30.5 23.8
Mean corpuscular volume (fl)   71.9   72.3 69.6
Platelet count (per μl)   1000   22,000 7000
White-cell count (per μl) 400 ,000 670   990 800
Differential count (per μl)
Neutrophils 1800–7000 50   50 10
Lymphocytes   590   930 790
Monocytes   30   0 10
Plasma cells — — 0 10 0
Eosinophils 5 50 0 5 50 0 0
Basophils  00 0  00 0 0
Reticulocytes (%) — — 0.5–2.5 <0.5 <0.5
Sodium (mmol/liter)   139   141 135
Potassium (mmol/liter) 3.6–5.1 4.3   4.4 4.8
Calcium (mg/dl) — —   9.7 9.4
Phosphorus (mg/dl) — —   3.1 3.7
Urea nitrogen (mg/dl) 6–20 14   15 13
Creatinine (mg/dl) 0.6–1.3 1.00   0.83 0.81
Alanine aminotransferase (U/liter) 10–50 83   77 44
Aspartate aminotransferase (U/liter) 15–41 49   42 21
Alkaline phosphatase (U/liter) 32–100 118   121 99
Total bilirubin (mg/dl) 0–1.2 0.4 0–1.0 0.6 0.5
Albumin (g/dl) 3.5–5.2 4.5   4.9 4.1
Globulin (g/dl)   3.1   3.2 3.6
Lactate dehydrogenase (U/liter) 98–192 282 11 10 270 163
Uric acid (mg/dl) — — 3.6–8.5 3.5 2.5
Prothrombin time (sec) 12.1–14.7 13.3   13.4 14.0
International normalized ratio   1.0   1.0 1.1
Partial-thromboplastin time (sec) — — 22. 6.0 28.1 28.9
d-dimer (ng/ml) — —   571 —
Fibrinogen (mg/dl) 200–470 355 15 0 474 —
Ferritin (μg/liter) — — 2 00 439 528
Iron (μg/dl) — — 45–160 170 —
Iron saturation (%) — — 14–50 51 —
Total iron-binding capacity (μg/dl) — — 23 4 335 —
Folate (ng/ml) — — >4.7 10.5 —
Vitamin B12 (pg/ml) — — >231 505 —
IgG (mg/dl) — —   1179 —
IgA (mg/dl) — —   237 —
IgM (mg/dl) — —   116 —
Serum protein electrophoresis — — Normal pattern Normal pattern —
Free kappa light chain (mg/liter) — —   16.0 —
Free lambda light chain (mg/liter) — —   10.7 —
Free kappa:lambda ratio — — 0.30–1.70 1.50 —
Hemoglobin electrophoresis (%)
Hemoglobin A — — 95.8–98.0 68.1 —
Hemoglobin A2 — — 2. .3 3.8 —
Hemoglobin F — — 0–0.9 0 —
Hemoglobin S — — 0 28.1 —",Severe acquired aplastic anemia after infection with severe acute respiratory syndrome coronavirus 2,Severe aplastic anemia in the presence of infection with severe acute respiratory syndrome coronavirus 2.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 21-year-old man presented to this hospital with a sore throat, epistaxis, and petechiae of the oropharynx.
One week before the current presentation, blood-filled blisters developed inside the patient's mouth, on the buccal mucosa. He had occasional bleeding from the mouth that resolved spontaneously. He consulted with his dentist, who was concerned about the possibility of impacted wisdom teeth. Two days before the current presentation, a sore throat developed. There was no difficulty with swallowing. On the day of the current presentation, epistaxis developed and did not resolve over a period of 2 hours.
The patient presented to another hospital for evaluation. On examination, the temperature was 37.1[degrees]C, the blood pressure 142/76 mm Hg, the pulse 98 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. He had blood in the nares and petechiae on the soft palate. There was a large ecchymosis on the left forearm that the patient attributed to carrying heavy boxes several days earlier. The remainder of the examination was normal. Laboratory testing revealed a hemoglobin level of 9.8 g per deciliter (reference range, 13.5 to 17.5), a platelet count of 1000 per microliter (reference range, 150,000 to 450,000), and a white-cell count of 670 per microliter (reference range, 4000 to 11,000). The absolute neutrophil count was 50 per microliter (reference range, 1800 to 7000). Blood levels of electrolytes and glucose were normal, as were results of tests for coagulation, renal function, and liver function. Other laboratory test results are shown in Table 1. The nose was packed to control the bleeding, and 1 unit of platelets was transfused. The patient was transferred to this hospital for additional evaluation and treatment.	
Table 1 
In the emergency department of this hospital, the patient reported a mild sore throat but no other symptoms; epistaxis had resolved with nasal packing. There was no fever, weight loss, rash, nausea, vomiting, or diarrhea. The patient had a history of sickle cell trait. He took no medications and had no known allergies. He had been living with his parents and younger brother since he had left his college campus at the start of the coronavirus disease 2019 (Covid-19) pandemic. He worked in a grocery store, and his only known sick contact was his mother, who had been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 2 months earlier. She had been isolated in a room in their home during her illness. The patient did not have any symptoms associated with Covid-19 and had never been tested for SARS-CoV-2 infection. His father and brother had been well. The family lived adjacent to a wooded region, and the patient had been hiking in northern New England 2 months before the current presentation. He had not noticed any tick bites. He had no animal contacts. The patient was born in Central America and had moved to a suburban region of New England at 3 years of age. He had previously traveled to Mexico and Canada. He was sexually active with female partners only. He did not smoke tobacco, drink alcohol, or use illicit drugs. His father had hypertension and hyperlipidemia, and paternal family members had sickle cell disease.
On examination, the patient appeared well. There were petechiae on the soft palate (Figure 1). There was no scleral icterus, lymphadenopathy, or hepatosplenomegaly. A large ecchymosis was present on the left forearm. The remainder of the examination was normal. Blood levels of folate and cobalamin were normal, as were results of serum protein electrophoresis and the ratio of free kappa to lambda light chains. Other laboratory test results are shown in Table 1. A radiograph of the chest and an ultrasound image of the upper abdomen were normal, without splenomegaly. Testing of a specimen obtained from the nasopharynx was positive for SARS-CoV-2 RNA; the patient was admitted to the hospital and placed in enhanced isolation. Examination of thick and thin peripheral-blood smears for babesia was negative.	
Figure 1
A second unit of platelets was transfused, and a diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 21-year-old man presented to this hospital with a sore throat, epistaxis, and petechiae of the oropharynx.
One week before the current presentation, blood-filled blisters developed inside the patient's mouth, on the buccal mucosa. He had occasional bleeding from the mouth that resolved spontaneously. He consulted with his dentist, who was concerned about the possibility of impacted wisdom teeth. Two days before the current presentation, a sore throat developed. There was no difficulty with swallowing. On the day of the current presentation, epistaxis developed and did not resolve over a period of 2 hours.
The patient presented to another hospital for evaluation. On examination, the temperature was 37.1[degrees]C, the blood pressure 142/76 mm Hg, the pulse 98 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. He had blood in the nares and petechiae on the soft palate. There was a large ecchymosis on the left forearm that the patient attributed to carrying heavy boxes several days earlier. The remainder of the examination was normal. Laboratory testing revealed a hemoglobin level of 9.8 g per deciliter (reference range, 13.5 to 17.5), a platelet count of 1000 per microliter (reference range, 150,000 to 450,000), and a white-cell count of 670 per microliter (reference range, 4000 to 11,000). The absolute neutrophil count was 50 per microliter (reference range, 1800 to 7000). Blood levels of electrolytes and glucose were normal, as were results of tests for coagulation, renal function, and liver function. Other laboratory test results are shown in Table 1. The nose was packed to control the bleeding, and 1 unit of platelets was transfused. The patient was transferred to this hospital for additional evaluation and treatment.	
Table 1 
In the emergency department of this hospital, the patient reported a mild sore throat but no other symptoms; epistaxis had resolved with nasal packing. There was no fever, weight loss, rash, nausea, vomiting, or diarrhea. The patient had a history of sickle cell trait. He took no medications and had no known allergies. He had been living with his parents and younger brother since he had left his college campus at the start of the coronavirus disease 2019 (Covid-19) pandemic. He worked in a grocery store, and his only known sick contact was his mother, who had been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 2 months earlier. She had been isolated in a room in their home during her illness. The patient did not have any symptoms associated with Covid-19 and had never been tested for SARS-CoV-2 infection. His father and brother had been well. The family lived adjacent to a wooded region, and the patient had been hiking in northern New England 2 months before the current presentation. He had not noticed any tick bites. He had no animal contacts. The patient was born in Central America and had moved to a suburban region of New England at 3 years of age. He had previously traveled to Mexico and Canada. He was sexually active with female partners only. He did not smoke tobacco, drink alcohol, or use illicit drugs. His father had hypertension and hyperlipidemia, and paternal family members had sickle cell disease.
On examination, the patient appeared well. There were petechiae on the soft palate (Figure 1). There was no scleral icterus, lymphadenopathy, or hepatosplenomegaly. A large ecchymosis was present on the left forearm. The remainder of the examination was normal. Blood levels of folate and cobalamin were normal, as were results of serum protein electrophoresis and the ratio of free kappa to lambda light chains. Other laboratory test results are shown in Table 1. A radiograph of the chest and an ultrasound image of the upper abdomen were normal, without splenomegaly. Testing of a specimen obtained from the nasopharynx was positive for SARS-CoV-2 RNA; the patient was admitted to the hospital and placed in enhanced isolation. Examination of thick and thin peripheral-blood smears for babesia was negative.	
Figure 1
A second unit of platelets was transfused, and a diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with a sore throat, epistaxis, and petechiae of the oropharynx, which are all signs of bleeding. Laboratory testing reveals a low hemoglobin level, a very low platelet count, and a low white-cell count, indicating anemia, thrombocytopenia, and leukopenia respectively. These findings suggest a problem with the bone marrow, as it is responsible for the production of these cells. The patient's history of sickle cell trait is not likely to be related, as sickle cell trait does not typically cause these symptoms. The patient's recent exposure to SARS-CoV-2 could potentially be related, as severe cases of COVID-19 have been associated with hematologic abnormalities, but the patient does not have any other symptoms of COVID-19. The patient's history of hiking in northern New England raises the possibility of a tick-borne disease, but the negative test for babesia makes this less likely. The patient's Central American origin and travel history could potentially be relevant if he was exposed to a disease endemic to those regions that could cause bone marrow suppression, but no specific disease is mentioned. Given these findings, the most likely diagnosis is aplastic anemia, a condition in which the bone marrow fails to produce sufficient new cells to replenish blood cells.\n\nDiagnosis: Aplastic anemia.""
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        ""content"": ""The patient is a young man presenting with a sore throat, epistaxis, petechiae of the oropharynx, and a large ecchymosis on the left forearm. He also has a significantly low platelet count and white blood cell count. The differential diagnosis for this patient includes aplastic anemia, leukemia, idiopathic thrombocytopenic purpura (ITP), and thrombotic thrombocytopenic purpura (TTP). The patient does not have any neurological symptoms or kidney damage, which makes TTP less likely. The patient also does not have any signs of infection or fever, which makes leukemia less likely. The patient's history of sickle cell trait could suggest a hematological disorder, but sickle cell trait does not typically cause low platelet or white blood cell counts. The patient's recent exposure to a family member with COVID-19 and positive test for SARS-CoV-2 RNA could suggest a viral-induced bone marrow suppression, but this is less likely given the severity of the patient's cytopenias and the lack of other typical symptoms of COVID-19. The patient's significant cytopenias, lack of splenomegaly, and absence of other specific symptoms or signs are most consistent with aplastic anemia, a condition characterized by pancytopenia and hypocellular bone marrow.\n\nDiagnosis: Aplastic anemia.""
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10.1056/NEJMcpc2107347,Case 30-2021: A 47-Year-Old Man with Recurrent Unilateral Head and Neck Pain,"Hemoglobin (g/dl)   13.7
Hematocrit (%)   38.4
White-cell count (per μl)   6800
Platelet count (per μl)   197,000
Erythrocyte sedimentation rate (mm/hr)   19
Anticardiolipin IgG (IgG phospholipid units)   3.8
Anticardiolipin IgM (IgM phospholipid units)   19.5
Cholesterol (mg/dl)
Total <200 196
Low-density lipoprotein <130 129
High-density lipoprotein   36
Triglycerides (mg/dl)   155
Urine toxicology screen Negative for amphetamines, 
barbiturates, benzodiazepines, 
cannabinoids, cocaine, opiates, 
and phencyclidine
Positive for acetaminophen 
and cannabinoids",Vascular Ehlers–Danlos syndrome.,Vascular Ehlers–Danlos syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 47-year-old right-handed man was evaluated at this hospital because of pain on the left side of the head and neck.
Six years before the current evaluation, the patient was admitted to this hospital with 1 week of headache, pain on the left side of the neck, numbness on the left side of the face, and dizziness. The pain was not relieved with the use of ibuprofen and had previously been evaluated and treated by a chiropractor. A neurologic examination revealed a slight decrease in taste and in sensation to touch and temperature on the left side of the face; a gait evaluation revealed a subtle leftward sway. Imaging studies were obtained.
Dr. Byung C. Yoon: Computed tomography (CT) of the head, performed after the administration of intravenous contrast material, revealed subtle foci of hypodensity in the left cerebellum, a finding suggestive of infarction. There was no evidence of arterial dissection, aneurysm, stenosis, or thrombotic occlusion. Magnetic resonance imaging (MRI) of the head, performed before and after the administration of intravenous contrast material, confirmed the presence of a left medial cerebellar infarct and a small left lateral medullary infarct (Figure 1A, 1B, and 1C).	
Figure 1
Dr. Dudzinski: The patient had normal results on cerebrospinal fluid (CSF) analysis, echocardiography, and a hypercoagulability panel, except for a mildly elevated level of anticardiolipin IgM (18.9 IgM phospholipid units; reference range, 0 to 15). During the hospital admission, lesions with a vesicular appearance developed on the left side of the lips and oral cavity, and the patient was treated with famciclovir. He was discharged home while receiving aspirin, with a follow-up visit scheduled in the neurology clinic.
One month later in the neurology clinic, the patient reported partial resolution of headache, persistent neck pain and ear pain with balance difficulty, and perioral paresthesia. There was diminished sensation on the left side of the face (similar to that observed during the previous examination). No oropharyngeal lesions were visible. An evaluation of gait and balance was normal.
Dr. Yoon: Magnetic resonance angiography of the head and neck, performed before and after the administration of intravenous contrast material, revealed expected evolution of the left cerebellar infarct and no new infarction. The left posterior inferior cerebellar artery was not visualized, possibly because of occlusion or slow blood flow.
Dr. Dudzinski: Repeat CSF analysis showed normal protein and glucose levels and 14 white cells per microliter (reference range, 0 to 5), of which 94% were lymphocytes. Gram's staining showed no organisms. CSF tests for borrelia and varicella DNA and for cytomegalovirus and herpes simplex virus antibodies were negative. Two days later, cerebral angiography revealed mild narrowing of the origin of the left vertebral artery. Tests for antinuclear antibodies, antineutrophil cytoplasmic antibodies, and anti-La and anti-Ro antibodies were negative, as was a rapid plasma reagin test.
The patient received follow-up care at another hospital until the current evaluation, when he presented to the emergency department of this hospital with 3 days of severe pain on exertion that affected the left side of the neck and left temporo-occipital region. The symptoms were similar to those he had reported in the past and were not relieved with the use of ibuprofen or marijuana. The head pain was described as pulsating and pounding, and it worsened when he was in the supine position.
The patient reported right flank pain; the onset of this pain had occurred with lifting of a heavy object and had just preceded the onset of headache. He also reported a tendency to bruise. The review of systems was otherwise normal. His medical history was notable for dyslipidemia. He had undergone repair of meniscus tears in both knees and repair of a traumatic dislocation of the right shoulder. Medications included rosuvastatin and gemfibrozil, as well as acetaminophen as needed. There were no known adverse reactions to medications. The patient was a self-employed laborer and lived with his wife and children in a suburb of Boston. He smoked cigars and marijuana occasionally, and he drank up to eight beers per day on weekends. His family history was notable for hypertension and dyslipidemia in both of his parents, as well as early-onset dementia in his father.
The temperature was 36.7[degrees]C, the blood pressure 176/119 mm Hg in both arms, the heart rate 72 beats per minute, and the oxygen saturation 98% while the patient was breathing ambient air. A neurologic examination revealed a mild decrease in coordination in the left hand but was otherwise normal. Blood levels of electrolytes, troponin T, C-reactive protein, lipoprotein(a), and glycated hemoglobin were normal, as were the prothrombin time, partial-thromboplastin time, and results of renal function tests. Urinalysis was also normal; other laboratory test results are shown in Table 1.	
Table 1 
Dr. Yoon: CT angiography of the head and neck, performed after the administration of intravenous contrast material, revealed dissection of the left vertebral artery, extending from the origin of the artery to the proximal V3 (upper cervical) segment, with a 2-mm pseudoaneurysm at the C2-C3 level (Figure 1D and 1E). There was no evidence of acute ischemia. MRI of the head, performed before and after the administration of intravenous contrast material, did not reveal any evidence of infarction or a perfusion abnormality. However, a T1-weighted image showed a focus of intrinsic hyperintensity along the left vertebral artery, a finding consistent with hemorrhage within the vessel wall from the dissection (Figure 1F).
Dr. Dudzinski: The patient was admitted to the neurology service. Control of the blood pressure required multiple medications. Echocardiography showed no cardiac, valvular, or aortic structural abnormality. Right flank pain recurred. Urinalysis showed 5 to 10 red cells per high-power field but was otherwise normal.
Dr. Yoon: CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed dissection of the right renal artery, extending from the origin of the artery to subsegmental renal arteries. Perinephric fat stranding was present on the right side, and there were areas of diminished enhancement in the right kidney. These findings were suggestive of infarction (Figure 2).	
Figure 2
Additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 47-year-old right-handed man was evaluated at this hospital because of pain on the left side of the head and neck.
Six years before the current evaluation, the patient was admitted to this hospital with 1 week of headache, pain on the left side of the neck, numbness on the left side of the face, and dizziness. The pain was not relieved with the use of ibuprofen and had previously been evaluated and treated by a chiropractor. A neurologic examination revealed a slight decrease in taste and in sensation to touch and temperature on the left side of the face; a gait evaluation revealed a subtle leftward sway. Imaging studies were obtained.
Dr. Byung C. Yoon: Computed tomography (CT) of the head, performed after the administration of intravenous contrast material, revealed subtle foci of hypodensity in the left cerebellum, a finding suggestive of infarction. There was no evidence of arterial dissection, aneurysm, stenosis, or thrombotic occlusion. Magnetic resonance imaging (MRI) of the head, performed before and after the administration of intravenous contrast material, confirmed the presence of a left medial cerebellar infarct and a small left lateral medullary infarct (Figure 1A, 1B, and 1C).	
Figure 1
Dr. Dudzinski: The patient had normal results on cerebrospinal fluid (CSF) analysis, echocardiography, and a hypercoagulability panel, except for a mildly elevated level of anticardiolipin IgM (18.9 IgM phospholipid units; reference range, 0 to 15). During the hospital admission, lesions with a vesicular appearance developed on the left side of the lips and oral cavity, and the patient was treated with famciclovir. He was discharged home while receiving aspirin, with a follow-up visit scheduled in the neurology clinic.
One month later in the neurology clinic, the patient reported partial resolution of headache, persistent neck pain and ear pain with balance difficulty, and perioral paresthesia. There was diminished sensation on the left side of the face (similar to that observed during the previous examination). No oropharyngeal lesions were visible. An evaluation of gait and balance was normal.
Dr. Yoon: Magnetic resonance angiography of the head and neck, performed before and after the administration of intravenous contrast material, revealed expected evolution of the left cerebellar infarct and no new infarction. The left posterior inferior cerebellar artery was not visualized, possibly because of occlusion or slow blood flow.
Dr. Dudzinski: Repeat CSF analysis showed normal protein and glucose levels and 14 white cells per microliter (reference range, 0 to 5), of which 94% were lymphocytes. Gram's staining showed no organisms. CSF tests for borrelia and varicella DNA and for cytomegalovirus and herpes simplex virus antibodies were negative. Two days later, cerebral angiography revealed mild narrowing of the origin of the left vertebral artery. Tests for antinuclear antibodies, antineutrophil cytoplasmic antibodies, and anti-La and anti-Ro antibodies were negative, as was a rapid plasma reagin test.
The patient received follow-up care at another hospital until the current evaluation, when he presented to the emergency department of this hospital with 3 days of severe pain on exertion that affected the left side of the neck and left temporo-occipital region. The symptoms were similar to those he had reported in the past and were not relieved with the use of ibuprofen or marijuana. The head pain was described as pulsating and pounding, and it worsened when he was in the supine position.
The patient reported right flank pain; the onset of this pain had occurred with lifting of a heavy object and had just preceded the onset of headache. He also reported a tendency to bruise. The review of systems was otherwise normal. His medical history was notable for dyslipidemia. He had undergone repair of meniscus tears in both knees and repair of a traumatic dislocation of the right shoulder. Medications included rosuvastatin and gemfibrozil, as well as acetaminophen as needed. There were no known adverse reactions to medications. The patient was a self-employed laborer and lived with his wife and children in a suburb of Boston. He smoked cigars and marijuana occasionally, and he drank up to eight beers per day on weekends. His family history was notable for hypertension and dyslipidemia in both of his parents, as well as early-onset dementia in his father.
The temperature was 36.7[degrees]C, the blood pressure 176/119 mm Hg in both arms, the heart rate 72 beats per minute, and the oxygen saturation 98% while the patient was breathing ambient air. A neurologic examination revealed a mild decrease in coordination in the left hand but was otherwise normal. Blood levels of electrolytes, troponin T, C-reactive protein, lipoprotein(a), and glycated hemoglobin were normal, as were the prothrombin time, partial-thromboplastin time, and results of renal function tests. Urinalysis was also normal; other laboratory test results are shown in Table 1.	
Table 1 
Dr. Yoon: CT angiography of the head and neck, performed after the administration of intravenous contrast material, revealed dissection of the left vertebral artery, extending from the origin of the artery to the proximal V3 (upper cervical) segment, with a 2-mm pseudoaneurysm at the C2-C3 level (Figure 1D and 1E). There was no evidence of acute ischemia. MRI of the head, performed before and after the administration of intravenous contrast material, did not reveal any evidence of infarction or a perfusion abnormality. However, a T1-weighted image showed a focus of intrinsic hyperintensity along the left vertebral artery, a finding consistent with hemorrhage within the vessel wall from the dissection (Figure 1F).
Dr. Dudzinski: The patient was admitted to the neurology service. Control of the blood pressure required multiple medications. Echocardiography showed no cardiac, valvular, or aortic structural abnormality. Right flank pain recurred. Urinalysis showed 5 to 10 red cells per high-power field but was otherwise normal.
Dr. Yoon: CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed dissection of the right renal artery, extending from the origin of the artery to subsegmental renal arteries. Perinephric fat stranding was present on the right side, and there were areas of diminished enhancement in the right kidney. These findings were suggestive of infarction (Figure 2).	
Figure 2
Additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of pain on the left side of the head and neck, along with the imaging findings of dissection of the left vertebral artery and right renal artery, suggest a diagnosis of fibromuscular dysplasia. This is a non-atherosclerotic, non-inflammatory disease of the blood vessels that results in abnormal growth within the wall of an artery. The disease most commonly affects the renal and carotid arteries, and can lead to arterial stenosis, aneurysm, or dissection. The patient's history of dyslipidemia and hypertension, as well as his lifestyle habits of occasional cigar and marijuana smoking and weekend alcohol consumption, may have contributed to the development of this condition.""
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        ""content"": ""The patient's symptoms of headache, neck pain, and numbness on the left side of the face, along with the imaging findings of left cerebellar infarct and left lateral medullary infarct, suggest a neurological issue. The subsequent development of lesions with a vesicular appearance on the left side of the lips and oral cavity indicate a possible viral infection, such as herpes simplex. However, the patient's symptoms persisted despite antiviral treatment. The patient's later presentation with severe pain on the left side of the neck and left temporo-occipital region, along with right flank pain, suggest a vascular issue. The imaging findings of dissection of the left vertebral artery and right renal artery confirm this. The patient's history of dyslipidemia and smoking, along with his family history of hypertension and dyslipidemia, increase his risk for vascular disease. Therefore, the patient's symptoms and imaging findings suggest a diagnosis of vascular dissection, likely due to underlying vascular disease.\n\nDiagnosis: Vascular dissection due to underlying vascular disease.""
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        ""content"": ""The patient is a 47-year-old man presenting with pain on the left side of the head and neck, as well as right flank pain. He has a history of similar symptoms six years prior, which were associated with a left medial cerebellar infarct and a small left lateral medullary infarct. His current symptoms are not relieved with ibuprofen or marijuana. His medical history is notable for dyslipidemia and he has a family history of hypertension and dyslipidemia. He smokes cigars and marijuana occasionally, and drinks up to eight beers per day on weekends. His current examination reveals a mild decrease in coordination in the left hand but is otherwise normal. CT angiography of the head and neck reveals dissection of the left vertebral artery, extending from the origin of the artery to the proximal V3 (upper cervical) segment, with a 2-mm pseudoaneurysm at the C2-C3 level. MRI of the head shows a focus of intrinsic hyperintensity along the left vertebral artery, consistent with hemorrhage within the vessel wall from the dissection. CT of the abdomen and pelvis reveals dissection of the right renal artery, extending from the origin of the artery to subsegmental renal arteries, suggestive of infarction. \n\nThe differential diagnosis for this patient includes fibromuscular dysplasia, vasculitis, and connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome. Given the patient's history of arterial dissections and infarctions, fibromuscular dysplasia is a strong possibility. However, this condition is more common in women and typically presents with hypertension, which this patient does not have. Vasculitis could also cause the patient's symptoms, but he does not have other systemic symptoms such as fever, weight loss, or malaise. Connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome could also cause arterial dissections, but these conditions typically present with other systemic features such as joint hypermobility, skin hyperextensibility, or ocular abnormalities, which this patient does not have. \n\nGiven the patient's history of multiple arterial dissections and infarctions, the most likely diagnosis is a genetic disorder of connective tissue that predisposes to arterial dissections. The most common of these is vascular Ehlers-Danlos syndrome (vEDS), which is caused by a mutation in the COL3A1 gene. This condition is characterized by arterial, intestinal, and/or uterine fragility. Patients with vEDS are at risk of spontaneous rupture of these organs, as well as arterial dissection and aneurysm. \n\nDiagnosis: Vascular Ehlers-Danlos syndrome (vEDS)""
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}",Vascular Ehlers-Danlos syndrome (vEDS),Y
10.1056/NEJMcpc2107346,Case 29-2021: A 12-Month-Old Boy with Fever and Developmental Regression,"White-cell count (per μl) 6000–17,500 8180 26,820
Differential count (per μl)
Neutrophils 150 600 3590 20,060
Lymphocytes 36 ,700 3980 4910
Monocytes 100–1900 530 460
Eosinophils  00 20 1150
Basophils   30 0
Platelet count (per μl)   388,000 682,000
Hemoglobin (g/dl) 10. .5 10.4 10.3
Hematocrit (%) 33. 9.0 34.4 33.8
Prothrombin time (sec)   13.1 13.8
Prothrombin-time international normalized 
ratio
  1.0 1.1
d-dimer (ng/ml)   3218 2389
Fibrinogen (mg/dl) 15 0 290 469
Ferritin (μg/liter) 3 00 3826 689
Erythrocyte sedimentation rate (mm/hr)   40 75
C-reactive protein (mg/liter)  .0 32.4 114.7
Procalcitonin (ng/ml) 0.00–0.08 — 0.59
Creatinine (mg/dl)† 0.30–1.00 0.22 0.21
Alanine aminotransferase (U/liter)   131 40
Aspartate aminotransferase (U/liter) 9–80 250 50
Alkaline phosphatase (U/liter) 142–335 163 176
Lactate dehydrogenase (U/liter) 13–60 498 490",Systemic juvenile idiopathic arthritis.,Systemic juvenile idiopathic arthritis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 12-month-old boy with Hirschsprung's disease was admitted to this hospital because of fever.
Fifteen days before the current admission, the patient had a temperature of 39.7[degrees]C. His parents noticed that he was fussy and less active than usual and that he had a decreased appetite along with several episodes of ""spitting up""; there was no vomiting or diarrhea. During the next 5 days, fever occurred daily and abated with the administration of acetaminophen or ibuprofen. Ten days before the current admission, a bowel movement with watery, nonbloody, foul-smelling, mustard-yellow stool occurred. The patient was brought to the emergency department of this hospital.
On examination, the patient was irritable. The abdomen was soft and nontender. There were well-circumscribed, erythematous, edematous plaques on the abdomen, legs, feet, and forearms. The alanine aminotransferase level was 131 U per liter (reference range, 10 to 55), the aspartate aminotransferase level 250 U per liter (reference range, 9 to 80), the ferritin level 3826 [mu]g per liter (reference range, 30 to 300), and the D-dimer level 3218 ng per milliliter (reference range,  ). The erythrocyte sedimentation rate was 40 mm per hour (reference range, 0 to 15); the white-cell count was normal. Other laboratory test results are shown in Table 1. A radiograph of the abdomen showed gas-filled loops of bowel. The rectum was irrigated, and intravenous piperacillin-tazobactam was administered. On the third hospital day, the patient was afebrile and able to take formula, and the diarrhea abated. He was discharged home with a prescription for a course of metronidazole.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
During the next 2 days, the patient had no fever or diarrhea. However, 4 days before the current admission, a day-care worker observed that the patient appeared tired. During the subsequent 3 days at home, fever again developed, with chills and a decreased appetite. The day before the current admission, the patient cried through the night. He was brought to the emergency department of this hospital for evaluation.
The parents reported that the patient was fussy and had poor sleep and generalized weakness; there was no diarrhea or new rash. The parents did not think that the patient was in pain. Additional history was obtained from the parents. The patient had met developmental milestones until 1 month earlier, when he had stopped crawling. He had previously been able to pull his body into a standing position, but he no longer attempted this maneuver. If he was placed in a standing position, he collapsed; if he was placed in a sitting position, he was able to stay upright. He had previously passed objects from hand to hand, but he had a new preference of holding objects with the left hand. Two days before this evaluation, the parents had noticed that the patient no longer walked with support; he seemed to dislike having his hands held.
The patient had cornea plana and a history of Hirschsprung's disease, for which he had undergone laparoscopic sigmoid colectomy and an anal pull-through procedure at 2 months of age. Four months before the current evaluation, an intermittent diffuse rash on the trunk, arms, and legs had developed. The rash was characterized by purplish and pinkish plaques that appeared and varied in intensity of color throughout the day; it did not seem to be itchy or painful and usually resolved within 24 hours without treatment.
Immunizations were up to date. Medications included metronidazole, acetaminophen, ibuprofen, and cetirizine, as well as carboxymethylcellulose eye drops; there were no known allergies to medications. The patient lived with his mother, father, and pet dog in a small town in New England, and he attended day care 5 days per week. His mother was healthy, and his father had irritable bowel syndrome and Poland syndrome (congenital aplasia of unilateral chest-wall muscles). His paternal grandmother had hypothyroidism, his maternal great-grandfather had had pancreatic cancer, his paternal great-grandfather had had breast cancer, a maternal second cousin had autism, and multiple maternal family members had Raynaud's phenomenon.
On examination, the temperature was 38.3[degrees]C, the blood pressure 113/52 mm Hg, the heart rate 166 beats per minute (normal range for age, 80 to 160), and the respiratory rate 30 breaths per minute (normal range for age, 30 to 60). The patient was diaphoretic and irritable, and he cried during the examination. He had rhinorrhea. The abdomen was not distended or tender. There was limited extension of the wrists and knees, as well as limited inversion and eversion of the feet. The ankles were mildly stiff, and the feet were mildly swollen. There were erythematous plaques on the abdomen, back, arms, and legs (Figure 1).	
Figure 1 Figure 1Opens a popup window	Opens a popup window	Opens a popup window
The ferritin and D-dimer levels remained elevated, and the aspartate aminotransferase and alanine aminotransferase levels were normal. The erythrocyte sedimentation rate was 75 mm per hour, the white-cell count 26,820 per microliter (reference range, 6000 to 17,500), and the platelet count 682,000 per microliter (reference range, 150,000 to 400,000). Blood cultures and urinalysis were normal. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative. Other laboratory test results are shown in Table 1.
Dr. Randheer Shailam: A radiograph of the chest and abdomen was normal. Ultrasonography of the abdomen revealed cholelithiasis and prominent lymph nodes in the right lower quadrant. Ultrasonography of the legs revealed a small amount of joint fluid in the hips and knees (Figure 2); the amount of fluid appeared to be within the normal range. Computed tomography (CT) of the abdomen, performed after the administration of intravenous contrast material, revealed a gallstone in the neck of the gallbladder, without gallbladder distention. There were a few prominent lymph nodes in the paraaortic, iliac, and inguinal regions (Figure 2). Transthoracic echocardiography showed normal coronary arteries.	
Figure 2 Figure 2Opens a popup window	Opens a popup window	Opens a popup window
Dr. Materne: The empirical administration of intravenous vancomycin, cefepime, and metronidazole was begun. During the next 3 days, the fever continued and the white-cell count remained elevated. On the seventh hospital day, the fever, leukocytosis, and elevation in levels of inflammatory markers persisted. The administration of antibiotic agents was stopped.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 12-month-old boy with Hirschsprung's disease was admitted to this hospital because of fever.
Fifteen days before the current admission, the patient had a temperature of 39.7[degrees]C. His parents noticed that he was fussy and less active than usual and that he had a decreased appetite along with several episodes of ""spitting up""; there was no vomiting or diarrhea. During the next 5 days, fever occurred daily and abated with the administration of acetaminophen or ibuprofen. Ten days before the current admission, a bowel movement with watery, nonbloody, foul-smelling, mustard-yellow stool occurred. The patient was brought to the emergency department of this hospital.
On examination, the patient was irritable. The abdomen was soft and nontender. There were well-circumscribed, erythematous, edematous plaques on the abdomen, legs, feet, and forearms. The alanine aminotransferase level was 131 U per liter (reference range, 10 to 55), the aspartate aminotransferase level 250 U per liter (reference range, 9 to 80), the ferritin level 3826 [mu]g per liter (reference range, 30 to 300), and the D-dimer level 3218 ng per milliliter (reference range,  ). The erythrocyte sedimentation rate was 40 mm per hour (reference range, 0 to 15); the white-cell count was normal. Other laboratory test results are shown in Table 1. A radiograph of the abdomen showed gas-filled loops of bowel. The rectum was irrigated, and intravenous piperacillin-tazobactam was administered. On the third hospital day, the patient was afebrile and able to take formula, and the diarrhea abated. He was discharged home with a prescription for a course of metronidazole.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
During the next 2 days, the patient had no fever or diarrhea. However, 4 days before the current admission, a day-care worker observed that the patient appeared tired. During the subsequent 3 days at home, fever again developed, with chills and a decreased appetite. The day before the current admission, the patient cried through the night. He was brought to the emergency department of this hospital for evaluation.
The parents reported that the patient was fussy and had poor sleep and generalized weakness; there was no diarrhea or new rash. The parents did not think that the patient was in pain. Additional history was obtained from the parents. The patient had met developmental milestones until 1 month earlier, when he had stopped crawling. He had previously been able to pull his body into a standing position, but he no longer attempted this maneuver. If he was placed in a standing position, he collapsed; if he was placed in a sitting position, he was able to stay upright. He had previously passed objects from hand to hand, but he had a new preference of holding objects with the left hand. Two days before this evaluation, the parents had noticed that the patient no longer walked with support; he seemed to dislike having his hands held.
The patient had cornea plana and a history of Hirschsprung's disease, for which he had undergone laparoscopic sigmoid colectomy and an anal pull-through procedure at 2 months of age. Four months before the current evaluation, an intermittent diffuse rash on the trunk, arms, and legs had developed. The rash was characterized by purplish and pinkish plaques that appeared and varied in intensity of color throughout the day; it did not seem to be itchy or painful and usually resolved within 24 hours without treatment.
Immunizations were up to date. Medications included metronidazole, acetaminophen, ibuprofen, and cetirizine, as well as carboxymethylcellulose eye drops; there were no known allergies to medications. The patient lived with his mother, father, and pet dog in a small town in New England, and he attended day care 5 days per week. His mother was healthy, and his father had irritable bowel syndrome and Poland syndrome (congenital aplasia of unilateral chest-wall muscles). His paternal grandmother had hypothyroidism, his maternal great-grandfather had had pancreatic cancer, his paternal great-grandfather had had breast cancer, a maternal second cousin had autism, and multiple maternal family members had Raynaud's phenomenon.
On examination, the temperature was 38.3[degrees]C, the blood pressure 113/52 mm Hg, the heart rate 166 beats per minute (normal range for age, 80 to 160), and the respiratory rate 30 breaths per minute (normal range for age, 30 to 60). The patient was diaphoretic and irritable, and he cried during the examination. He had rhinorrhea. The abdomen was not distended or tender. There was limited extension of the wrists and knees, as well as limited inversion and eversion of the feet. The ankles were mildly stiff, and the feet were mildly swollen. There were erythematous plaques on the abdomen, back, arms, and legs (Figure 1).	
Figure 1 Figure 1Opens a popup window	Opens a popup window	Opens a popup window
The ferritin and D-dimer levels remained elevated, and the aspartate aminotransferase and alanine aminotransferase levels were normal. The erythrocyte sedimentation rate was 75 mm per hour, the white-cell count 26,820 per microliter (reference range, 6000 to 17,500), and the platelet count 682,000 per microliter (reference range, 150,000 to 400,000). Blood cultures and urinalysis were normal. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative. Other laboratory test results are shown in Table 1.
Dr. Randheer Shailam: A radiograph of the chest and abdomen was normal. Ultrasonography of the abdomen revealed cholelithiasis and prominent lymph nodes in the right lower quadrant. Ultrasonography of the legs revealed a small amount of joint fluid in the hips and knees (Figure 2); the amount of fluid appeared to be within the normal range. Computed tomography (CT) of the abdomen, performed after the administration of intravenous contrast material, revealed a gallstone in the neck of the gallbladder, without gallbladder distention. There were a few prominent lymph nodes in the paraaortic, iliac, and inguinal regions (Figure 2). Transthoracic echocardiography showed normal coronary arteries.	
Figure 2 Figure 2Opens a popup window	Opens a popup window	Opens a popup window
Dr. Materne: The empirical administration of intravenous vancomycin, cefepime, and metronidazole was begun. During the next 3 days, the fever continued and the white-cell count remained elevated. On the seventh hospital day, the fever, leukocytosis, and elevation in levels of inflammatory markers persisted. The administration of antibiotic agents was stopped.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Juvenile Idiopathic Arthritis (Systemic Onset)\n\nThe patient's symptoms of fever, rash, and joint pain are consistent with systemic juvenile idiopathic arthritis (sJIA). The elevated ferritin level, leukocytosis, and elevated erythrocyte sedimentation rate are also indicative of sJIA. The negative infectious workup and lack of response to antibiotics further support this diagnosis. The patient's age and the chronic nature of his symptoms are also consistent with sJIA.""
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        ""content"": ""The patient's symptoms include fever, irritability, decreased activity, decreased appetite, and a rash. He also has a history of Hirschsprung's disease. The patient's lab results show elevated ferritin and D-dimer levels, as well as elevated erythrocyte sedimentation rate, white-cell count, and platelet count. These findings suggest a systemic inflammatory response. The patient's symptoms and lab results are consistent with Kawasaki disease, a condition that causes inflammation in the walls of medium-sized arteries throughout the body. However, the patient's age and the presence of gastrointestinal symptoms suggest a different diagnosis. The patient's symptoms, lab results, and history are consistent with multisystem inflammatory syndrome in children (MIS-C), a condition associated with SARS-CoV-2 infection that causes inflammation in multiple organs. The patient's negative SARS-CoV-2 RNA test does not rule out this diagnosis, as MIS-C can occur weeks after a SARS-CoV-2 infection, and the patient may no longer test positive for the virus.\n\nDiagnosis: Multisystem Inflammatory Syndrome in Children (MIS-C)""
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        ""content"": ""The patient is a 12-month-old boy with a history of Hirschsprung's disease who presents with fever, irritability, decreased activity, decreased appetite, and a rash. He also has elevated liver enzymes, ferritin, D-dimer, and erythrocyte sedimentation rate. The differential diagnosis for this patient includes sepsis, autoimmune disease, malignancy, and Kawasaki disease. The patient's blood cultures and urinalysis are normal, making sepsis less likely. The patient's symptoms of fever, rash, and elevated inflammatory markers could be consistent with an autoimmune disease, but the patient does not have any other symptoms such as joint pain or organ-specific symptoms that would suggest a specific autoimmune disease. Malignancy could present with fever and elevated inflammatory markers, but the patient does not have any symptoms such as weight loss, night sweats, or lymphadenopathy that would suggest malignancy. Kawasaki disease could present with fever and rash, but the patient does not have the other classic symptoms of Kawasaki disease such as conjunctivitis, changes in the lips or oral cavity, changes in the extremities, or cervical lymphadenopathy. The patient's symptoms of fever, rash, and elevated inflammatory markers, along with his history of Hirschsprung's disease, suggest the possibility of an autoinflammatory disease. The patient's symptoms and laboratory findings are consistent with the diagnosis of neonatal onset multisystem inflammatory disease (NOMID), a severe form of cryopyrin-associated periodic syndrome (CAPS). NOMID is characterized by fever, rash, and elevated inflammatory markers, and can also cause joint symptoms, as seen in this patient. The patient's history of Hirschsprung's disease could also be related to his underlying autoinflammatory disease, as some studies have suggested a possible association between Hirschsprung's disease and autoinflammatory diseases.\n\nDiagnosis: Neonatal onset multisystem inflammatory disease (NOMID).""
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}",Neonatal onset multisystem inflammatory disease (NOMID),N
10.1056/NEJMcpc2107350,Case 28-2021: A 37-Year-Old Woman with Covid-19 and Suicidal Ideation,"Hemoglobin (g/dl)   13.2
Hematocrit (%)   38.2
Platelet count (per μl)   174,000
White-cell count (per μl)   6660
Differential count (per μl)
Neutrophils   5030
Lymphocytes   1570
Monocytes   60
Urea nitrogen (mg/dl)   3
Creatinine (mg/dl)   0.55
Alanine aminotransferase (U/liter)   28
Aspartate aminotransferase (U/liter)   34
Lactate dehydrogenase (U/liter) 11 10 318
Creatine kinase (U/liter)   154
High-sensitivity troponin T (ng/liter) 0–9 <6
Ferritin (μg/liter) 1 00 267
d-dimer (ng/ml)   551
C-reactive protein (mg/liter)  .0 51.1
Serum toxicology tests
Acetaminophen (μg/ml) 0. 5.0 8.7
Ethanol (mg/dl) 0 0
Salicylates (mg/dl) 0. 0.0 <0.3
Tricyclic antidepressants Negative Negative
Urine toxicology tests
Amphetamines Negative Negative
Barbiturates Negative Negative
Benzodiazepines Negative Negative
Cannabinoids Negative Negative
Cocaine metabolites Negative Negative
Opiates Negative Negative","Fear associated with coronavirus disease 2019 (Covid-19), causing suicidal ideation.",Understandable psychosocial distress in the context of serious illness during the Covid-19 pandemic,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 37-year-old woman was admitted to this hospital because of fever, shortness of breath, and suicidal ideation in March 2020, during the pandemic of coronavirus disease 2019 (Covid-19).
Ten days before this admission, fever, fatigue, sore throat, cough, and myalgias developed. The symptoms did not abate after the patient took aspirin and acetaminophen. Five days before this admission, she sought evaluation at the urgent care clinic of this hospital because Covid-19 had been diagnosed in two coworkers. A test for Covid-19 was not performed because of limited test availability; tests for influenza A and B viruses and respiratory syncytial virus were not performed because of a statewide shortage of nasopharyngeal swabs. The patient was instructed to quarantine at home.
During the next 5 days, the patient quarantined in a room in her apartment. Her husband periodically brought food to the door of the room. The fever, fatigue, sore throat, cough, and myalgias persisted; new shortness of breath and anosmia developed. She had decreased appetite, and she consumed minimal food and drink.
One day before this admission, nausea, vomiting, and diarrhea developed, and the patient sought evaluation at the emergency department of another hospital. Intravenous fluid, ondansetron, and ketorolac were administered, and she was discharged home with instructions to continue to quarantine.
On the day of admission, the patient had dizziness while standing, as well as shortness of breath, and she returned to the urgent care clinic of this hospital. The temperature was 38.7[degrees]C, the heart rate 127 beats per minute, the respiratory rate 38 breaths per minute, and the oxygen saturation 97% while she was breathing ambient air. The patient was anxious and tearful. The lungs were clear on auscultation. Intravenous fluid, ondansetron, and oral acetaminophen were administered. The dizziness resolved, and the fever, shortness of breath, and anxiety decreased. The patient was advised to return home to quarantine; however, she disclosed that if she were sent home, she planned to overdose on medications to die by suicide because of her anxiety and feelings of sadness and loneliness. Owing to concern about the patient's risk of harming herself, an order authorizing temporary involuntary hospitalization was implemented. Emergency medical services were called, and the patient was brought to the emergency department.
On evaluation in the emergency department, the patient reported anxiety, palpitations, and shortness of breath and noted that her anxiety and feelings of isolation and loneliness had developed during quarantine. She also reported poor sleep, decreased energy, and anhedonia. The patient described that she felt like a burden to her husband and was terrified that she would transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to her children, including her 4-year-old son, who had been born prematurely and had a congenital pulmonary condition.
In addition, the patient reported a 1-week history of new, recurring nightmares in which she would see herself playing with her own severed body parts; these nightmares occurred more frequently during periods of high fever. She intermittently had the sensation that someone was in the room with her while she was awake, even though she was aware that she was alone. She disclosed that, on the previous day, she had had new suicidal ideation associated with fear of transmitting SARS-CoV-2 to her family and that she had taken five aspirin-paracetamol-caffeine pills at once. There had been no history of suicidal ideation or attempt, self-harm, or homicidal ideation.
The patient had a history of depression and panic attacks when she was a teenager and had been treated for less than 1 year with a medication that she could not recall; the symptoms had resolved by 19 years of age, and there had been no mental health follow-up. She also had a history of migraines, which occurred four times per week. She took aspirin, acetaminophen, and aspirin-paracetamol-caffeine as needed; there were no known drug allergies. The patient was born in Central America and had been living in the United States for 19 years. She lived with her husband, four children, and mother-in-law in an urban area of New England in a community that was predominantly Latinx and that had a high rate of Covid-19-related infections and deaths. The patient did not complete high school while she was living in Central America and was currently employed full time in a food-production factory. She reported that she enjoyed her job but that she had been reluctant to work during the Covid-19 pandemic because of concern about becoming ill; however, she described that she felt obligated to work to support her family. The patient did not smoke cigarettes, drink alcohol, or use illicit drugs. Her mother had died from cancer.
On examination, the temperature was 38.2[degrees]C, the blood pressure 148/84 mm Hg, the heart rate 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. She appeared well-groomed and fatigued, and she was tearful with a depressed and dysphoric mood. Her behavior was described as ""sullen,"" and there was limited eye contact and reduced psychomotor activity. Her speech, in Spanish, was fluent but was slow and mumbling, with reduced prosody. She had no derailment of thought, delusions, or obsessions, but she ruminated on her nightmares. She stated that she had no current suicidal ideation but that she might attempt suicide if she had to return to her children and expose them to SARS-CoV-2 again.
Nucleic acid testing of a nasopharyngeal swab for SARS-CoV-2 RNA was positive. Additional laboratory test results are shown in Table 1. Radiography of the chest revealed ground-glass opacities in the right middle and lower lobes and in the left lower lobe. Intravenous ceftriaxone, oral azithromycin, atorvastatin, and hydroxychloroquine were administered, and the patient was admitted to the hospital.	
Table 1
Management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 37-year-old woman was admitted to this hospital because of fever, shortness of breath, and suicidal ideation in March 2020, during the pandemic of coronavirus disease 2019 (Covid-19).
Ten days before this admission, fever, fatigue, sore throat, cough, and myalgias developed. The symptoms did not abate after the patient took aspirin and acetaminophen. Five days before this admission, she sought evaluation at the urgent care clinic of this hospital because Covid-19 had been diagnosed in two coworkers. A test for Covid-19 was not performed because of limited test availability; tests for influenza A and B viruses and respiratory syncytial virus were not performed because of a statewide shortage of nasopharyngeal swabs. The patient was instructed to quarantine at home.
During the next 5 days, the patient quarantined in a room in her apartment. Her husband periodically brought food to the door of the room. The fever, fatigue, sore throat, cough, and myalgias persisted; new shortness of breath and anosmia developed. She had decreased appetite, and she consumed minimal food and drink.
One day before this admission, nausea, vomiting, and diarrhea developed, and the patient sought evaluation at the emergency department of another hospital. Intravenous fluid, ondansetron, and ketorolac were administered, and she was discharged home with instructions to continue to quarantine.
On the day of admission, the patient had dizziness while standing, as well as shortness of breath, and she returned to the urgent care clinic of this hospital. The temperature was 38.7[degrees]C, the heart rate 127 beats per minute, the respiratory rate 38 breaths per minute, and the oxygen saturation 97% while she was breathing ambient air. The patient was anxious and tearful. The lungs were clear on auscultation. Intravenous fluid, ondansetron, and oral acetaminophen were administered. The dizziness resolved, and the fever, shortness of breath, and anxiety decreased. The patient was advised to return home to quarantine; however, she disclosed that if she were sent home, she planned to overdose on medications to die by suicide because of her anxiety and feelings of sadness and loneliness. Owing to concern about the patient's risk of harming herself, an order authorizing temporary involuntary hospitalization was implemented. Emergency medical services were called, and the patient was brought to the emergency department.
On evaluation in the emergency department, the patient reported anxiety, palpitations, and shortness of breath and noted that her anxiety and feelings of isolation and loneliness had developed during quarantine. She also reported poor sleep, decreased energy, and anhedonia. The patient described that she felt like a burden to her husband and was terrified that she would transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to her children, including her 4-year-old son, who had been born prematurely and had a congenital pulmonary condition.
In addition, the patient reported a 1-week history of new, recurring nightmares in which she would see herself playing with her own severed body parts; these nightmares occurred more frequently during periods of high fever. She intermittently had the sensation that someone was in the room with her while she was awake, even though she was aware that she was alone. She disclosed that, on the previous day, she had had new suicidal ideation associated with fear of transmitting SARS-CoV-2 to her family and that she had taken five aspirin-paracetamol-caffeine pills at once. There had been no history of suicidal ideation or attempt, self-harm, or homicidal ideation.
The patient had a history of depression and panic attacks when she was a teenager and had been treated for less than 1 year with a medication that she could not recall; the symptoms had resolved by 19 years of age, and there had been no mental health follow-up. She also had a history of migraines, which occurred four times per week. She took aspirin, acetaminophen, and aspirin-paracetamol-caffeine as needed; there were no known drug allergies. The patient was born in Central America and had been living in the United States for 19 years. She lived with her husband, four children, and mother-in-law in an urban area of New England in a community that was predominantly Latinx and that had a high rate of Covid-19-related infections and deaths. The patient did not complete high school while she was living in Central America and was currently employed full time in a food-production factory. She reported that she enjoyed her job but that she had been reluctant to work during the Covid-19 pandemic because of concern about becoming ill; however, she described that she felt obligated to work to support her family. The patient did not smoke cigarettes, drink alcohol, or use illicit drugs. Her mother had died from cancer.
On examination, the temperature was 38.2[degrees]C, the blood pressure 148/84 mm Hg, the heart rate 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. She appeared well-groomed and fatigued, and she was tearful with a depressed and dysphoric mood. Her behavior was described as ""sullen,"" and there was limited eye contact and reduced psychomotor activity. Her speech, in Spanish, was fluent but was slow and mumbling, with reduced prosody. She had no derailment of thought, delusions, or obsessions, but she ruminated on her nightmares. She stated that she had no current suicidal ideation but that she might attempt suicide if she had to return to her children and expose them to SARS-CoV-2 again.
Nucleic acid testing of a nasopharyngeal swab for SARS-CoV-2 RNA was positive. Additional laboratory test results are shown in Table 1. Radiography of the chest revealed ground-glass opacities in the right middle and lower lobes and in the left lower lobe. Intravenous ceftriaxone, oral azithromycin, atorvastatin, and hydroxychloroquine were administered, and the patient was admitted to the hospital.	
Table 1
Management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 37-year-old woman presenting with fever, shortness of breath, and suicidal ideation. She has a history of depression and panic attacks, and her symptoms have developed during the Covid-19 pandemic. She has tested positive for SARS-CoV-2 and has been experiencing symptoms consistent with Covid-19, including fever, fatigue, sore throat, cough, myalgias, shortness of breath, and anosmia. She also has new gastrointestinal symptoms of nausea, vomiting, and diarrhea. Her chest radiography reveals ground-glass opacities in the right middle and lower lobes and in the left lower lobe, which is consistent with Covid-19 pneumonia. The patient's suicidal ideation and feelings of isolation and loneliness have developed during her quarantine period. She has a fear of transmitting the virus to her family, particularly her 4-year-old son who has a congenital pulmonary condition. She has also been experiencing new, recurring nightmares and has had the sensation that someone is in the room with her while she is awake. Given her positive test for SARS-CoV-2, her symptoms, and her mental health history, the most likely diagnosis is Covid-19 with associated acute stress reaction and exacerbation of underlying mental health conditions.\n\nDiagnosis: Covid-19 with associated acute stress reaction and exacerbation of underlying mental health conditions.""
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10.1056/NEJMcpc2103458,Case 26-2021: A 49-Year-Old Man with Relapsed Acute Myeloid Leukemia,"Hemoglobin (g/dl)   14.6
Hematocrit (%)   43.2
White-cell count (per μl)   5830
Differential count (%)
Neutrophils   12.6
Lymphocytes   39.7
Reactive lymphocytes 0 2.7
Eosinophils   0.9
Basophils   0.9
Monocytes   1.8
Blasts 0 39.6
Platelet count (per μl)   44,000
Creatinine (mg/dl)   1.00
Urea nitrogen (mg/dl)   11
Aspartate aminotransferase (U/liter)   25
Alanine aminotransferase (U/liter)   21
Alkaline phosphatase (U/liter)   97
Total bilirubin (mg/dl)  0.1
Albumin (g/dl)   4.0
Globulin (g/dl)   2.9
Lactate dehydrogenase (U/liter) 11 10 459
Uric acid (mg/dl) 3.6–8.5 5.5
Glycated hemoglobin (%) 4.3–6.4 6.0","Relapsed acute myeloid leukemia (with wild-type 
NPM1 and newly identified internal tandem duplication mutation in FLT3)",Relapsed acute myeloid leukemia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 49-year-old man was evaluated at this hospital because of relapsed acute myeloid leukemia (AML).
Fourteen months before the current presentation, the patient was evaluated at another hospital because of pain in the right upper quadrant that had begun 4 days earlier and was associated with nausea and vomiting. Abdominal imaging revealed evidence of acute cholecystitis. Initial laboratory test results showed peripheral blasts that were suggestive of acute leukemia. The patient was transferred to a second hospital for additional evaluation. At the second hospital, abdominal imaging confirmed acute cholecystitis, and a calculus was found lodged in the neck of the gallbladder. The white-cell count was 4200 per microliter (reference range, 4200 to 9900), of which 40% were blasts. A peripheral-blood smear was notable for circulating blasts with Auer rods. The hemoglobin level was 11.7 g per deciliter (reference range, 13.0 to 17.4), and the platelet count was 22,000 per microliter (reference range, 140,000 to 440,000). A bone marrow biopsy was performed, followed by laparoscopic cholecystectomy.
Dr. Andrew M. Crabbe: The bone marrow biopsy performed at the second hospital was inadequate owing to the small size of the specimen; however, intact bone marrow particles showed a cellularity of 95 to 100%. A 300-cell differential count on combined touch-imprint and aspirate smears showed 39% blasts, 3% promyelocytes, 19% neutrophils and precursors, 5% erythroid precursors, 30% lymphocytes, 3% monocytes, 1% eosinophils, and less than 1% basophils. The blasts were medium in size, with irregular nuclear contours, moderately clumped chromatin, occasional prominent small nucleoli, and scant granular cytoplasm. Auer rods were identified. Flow cytometry of the peripheral blood identified myeloid blasts that were negative for CD34 and HLA-DR and positive for CD117, CD33, CD13, and myeloperoxidase. Cytogenetic analysis of the peripheral blood with the use of fluorescence in situ hybridization (FISH) revealed a normal karyotype (46,XY) and no evidence of a t(15;17) chromosomal translocation. Molecular testing of the peripheral blood by means of dedicated polymerase-chain-reaction (PCR) testing and next-generation sequencing identified mutations in NPM1, DNMT3A, and NRAS and did not identify mutations in FLT3, IDH1, or IDH2. The overall findings of this testing were consistent with the World Health Organization classification of AML with mutated NPM1.
Dr. Newcomb: Induction chemotherapy with 7 days of cytarabine and 3 days of daunorubicin was administered. On day 34 after the initiation of chemotherapy, the absolute neutrophil count was 2.2 per microliter (reference range, 1.5 to 7.5), and the platelet count was 536,000 per microliter. A bone marrow biopsy performed on day 37 after initiation of chemotherapy revealed hypercellular marrow with maturing trilineage hematopoiesis. There was no morphologic or phenotypic evidence of persistent or relapsed AML. A 300-cell sample of the bone marrow aspirate contained less than 1% blasts. Consolidation chemotherapy with four cycles of high-dose cytarabine was completed 8 months before the current presentation.
Dr. Crabbe: A bone marrow biopsy performed after the final cycle of chemotherapy revealed normocellular marrow with trilineage hematopoiesis; there was no morphologic or phenotypic evidence of AML. Next-generation sequencing of the bone marrow biopsy specimen revealed no pathogenic mutations.
Dr. Newcomb: The patient remained well for 7 months. One month before the current presentation, mild leukopenia developed, and more frequent laboratory monitoring was instituted. One week before the current presentation, the white-cell count was 2600 per microliter (reference range, 4000 to 10,000), of which 13% were peripheral blasts. The patient was referred to this hospital for evaluation.
On presentation to this hospital, the patient reported a 3-week history of progressive fatigue, dyspnea on exertion, exercise intolerance, widespread muscle aches, and night sweats. He noted that similar symptoms had preceded his initial diagnosis.
Medical history included obesity and hypertension. The patient was not taking medications on a regular basis. He was allergic to chlorhexidine, which caused rash. He lived in rural New England with his wife and four children. He worked as a software engineer. He did not smoke, and he drank alcohol rarely. His mother had coronary artery disease, and a sister had had a stroke. He had three other siblings who were healthy. There was no family history of leukemia or other hematologic disorders.
On examination, the patient appeared well. The temperature was 35.7[degrees]C. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 43. No lymphadenopathy, rashes, or skin lesions were present. The remainder of the examination was normal. The white-cell count was 5830 per microliter (reference range, 4500 to 11,000), of which 39.6% were blasts. Additional laboratory test results are shown in Table 1. A bone marrow biopsy was performed, and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 49-year-old man was evaluated at this hospital because of relapsed acute myeloid leukemia (AML).
Fourteen months before the current presentation, the patient was evaluated at another hospital because of pain in the right upper quadrant that had begun 4 days earlier and was associated with nausea and vomiting. Abdominal imaging revealed evidence of acute cholecystitis. Initial laboratory test results showed peripheral blasts that were suggestive of acute leukemia. The patient was transferred to a second hospital for additional evaluation. At the second hospital, abdominal imaging confirmed acute cholecystitis, and a calculus was found lodged in the neck of the gallbladder. The white-cell count was 4200 per microliter (reference range, 4200 to 9900), of which 40% were blasts. A peripheral-blood smear was notable for circulating blasts with Auer rods. The hemoglobin level was 11.7 g per deciliter (reference range, 13.0 to 17.4), and the platelet count was 22,000 per microliter (reference range, 140,000 to 440,000). A bone marrow biopsy was performed, followed by laparoscopic cholecystectomy.
Dr. Andrew M. Crabbe: The bone marrow biopsy performed at the second hospital was inadequate owing to the small size of the specimen; however, intact bone marrow particles showed a cellularity of 95 to 100%. A 300-cell differential count on combined touch-imprint and aspirate smears showed 39% blasts, 3% promyelocytes, 19% neutrophils and precursors, 5% erythroid precursors, 30% lymphocytes, 3% monocytes, 1% eosinophils, and less than 1% basophils. The blasts were medium in size, with irregular nuclear contours, moderately clumped chromatin, occasional prominent small nucleoli, and scant granular cytoplasm. Auer rods were identified. Flow cytometry of the peripheral blood identified myeloid blasts that were negative for CD34 and HLA-DR and positive for CD117, CD33, CD13, and myeloperoxidase. Cytogenetic analysis of the peripheral blood with the use of fluorescence in situ hybridization (FISH) revealed a normal karyotype (46,XY) and no evidence of a t(15;17) chromosomal translocation. Molecular testing of the peripheral blood by means of dedicated polymerase-chain-reaction (PCR) testing and next-generation sequencing identified mutations in NPM1, DNMT3A, and NRAS and did not identify mutations in FLT3, IDH1, or IDH2. The overall findings of this testing were consistent with the World Health Organization classification of AML with mutated NPM1.
Dr. Newcomb: Induction chemotherapy with 7 days of cytarabine and 3 days of daunorubicin was administered. On day 34 after the initiation of chemotherapy, the absolute neutrophil count was 2.2 per microliter (reference range, 1.5 to 7.5), and the platelet count was 536,000 per microliter. A bone marrow biopsy performed on day 37 after initiation of chemotherapy revealed hypercellular marrow with maturing trilineage hematopoiesis. There was no morphologic or phenotypic evidence of persistent or relapsed AML. A 300-cell sample of the bone marrow aspirate contained less than 1% blasts. Consolidation chemotherapy with four cycles of high-dose cytarabine was completed 8 months before the current presentation.
Dr. Crabbe: A bone marrow biopsy performed after the final cycle of chemotherapy revealed normocellular marrow with trilineage hematopoiesis; there was no morphologic or phenotypic evidence of AML. Next-generation sequencing of the bone marrow biopsy specimen revealed no pathogenic mutations.
Dr. Newcomb: The patient remained well for 7 months. One month before the current presentation, mild leukopenia developed, and more frequent laboratory monitoring was instituted. One week before the current presentation, the white-cell count was 2600 per microliter (reference range, 4000 to 10,000), of which 13% were peripheral blasts. The patient was referred to this hospital for evaluation.
On presentation to this hospital, the patient reported a 3-week history of progressive fatigue, dyspnea on exertion, exercise intolerance, widespread muscle aches, and night sweats. He noted that similar symptoms had preceded his initial diagnosis.
Medical history included obesity and hypertension. The patient was not taking medications on a regular basis. He was allergic to chlorhexidine, which caused rash. He lived in rural New England with his wife and four children. He worked as a software engineer. He did not smoke, and he drank alcohol rarely. His mother had coronary artery disease, and a sister had had a stroke. He had three other siblings who were healthy. There was no family history of leukemia or other hematologic disorders.
On examination, the patient appeared well. The temperature was 35.7[degrees]C. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 43. No lymphadenopathy, rashes, or skin lesions were present. The remainder of the examination was normal. The white-cell count was 5830 per microliter (reference range, 4500 to 11,000), of which 39.6% were blasts. Additional laboratory test results are shown in Table 1. A bone marrow biopsy was performed, and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Relapsed Acute Myeloid Leukemia (AML)\n\nThe patient was previously diagnosed with AML, as indicated by the presence of peripheral blasts with Auer rods, and mutations in NPM1, DNMT3A, and NRAS. After undergoing induction and consolidation chemotherapy, the patient was in remission with no morphologic or phenotypic evidence of AML. However, the patient's recent symptoms of fatigue, dyspnea, exercise intolerance, muscle aches, and night sweats, which were similar to those preceding his initial diagnosis, suggest a relapse. This is confirmed by the presence of 39.6% blasts in his white blood cell count.""
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        ""content"": ""Relapsed Acute Myeloid Leukemia (AML)\n\nThe patient's history of AML, along with the presence of peripheral blasts and symptoms such as fatigue, dyspnea, exercise intolerance, muscle aches, and night sweats, strongly suggest a relapse of his AML. The absence of lymphadenopathy, rashes, or skin lesions makes lymphoma or skin cancer less likely. The patient's obesity and hypertension do not directly contribute to the differential diagnosis in this case. The patient's family history is also not indicative of a genetic disorder that could explain his symptoms. Therefore, given the patient's history and presentation, the most likely diagnosis is a relapse of his AML.""
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10.1056/NEJMcpc2100282,Case 25-2021: A 48-Year-Old Man with Fatigue and Leg Swelling,"Hemoglobin (g/dl)   15.8
Hematocrit (%)   45.7
White-cell count (per μl)   3610
Platelet count (per μl)   82,000
Mean corpuscular volume (fl)   103.9
Glycated hemoglobin (%) 4.3–6.4 11.6
Sodium (mmol/liter)   130
Potassium (mmol/liter)   4.8
Chloride (mmol/liter)   89
Carbon dioxide (mmol/liter)   26
Anion gap (mmol/liter)   15
Glucose (mg/dl)   402
Creatinine (mg/dl)   0.70
Urea nitrogen (mg/dl)   9
Aspartate aminotransferase (U/liter)   92
Alanine aminotransferase (U/liter)   37
Alkaline phosphatase (U/liter)   172
Total bilirubin (mg/dl)  1.8
Albumin (g/dl)   3.9
Total protein (g/dl) 6. .3 8.1
Peritoneal fluid
Color NA Yellow
Red-cell count (per μl) NA <3000
White-cell count (per μl) NA 492
Differential count (per μl)
Neutrophils NA 0
Lymphocytes NA 260
Reactive lymphocytes NA 0
Monocytes NA 63
Eosinophils NA 0
Basophils NA 9
Macrophages or lining cells NA 157
Albumin (g/dl) NA 1.0
Total protein (g/dl) NA 1.8
Urine
Ketones Negative 2+
Glucose Negative 3+
Bilirubin Negative 1+
Blood Negative Negative
pH   6.5
Nitrites Negative Negative
Leukocyte esterase Negative Negative
Specific gravity   1.038",Hereditary hemochromatosis.,Systemic iron-overload syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old man was admitted to this hospital because of fatigue and swelling in both legs.
The patient had been well until 8 months before the current admission, when fatigue and lethargy developed. He thought the fatigue was associated with alcohol consumption and reduced his intake to 12 beers weekly; before this, he had consumed 24 beers weekly for 15 years. Three months before the current admission, the patient's weight had decreased by 9.1 kg. However, 3 weeks before this admission, the weight had increased by 9.6 kg and swelling developed in both legs. He thought the weight gain was related to diet changes, including consumption of pizza, pasta, and soup, during the coronavirus disease 2019 pandemic.
One week before the current admission, the patient was evaluated by his primary care physician. He was instructed to elevate his legs, wear compression stockings, and decrease dietary sodium to 2 g daily. On the day of the current admission, the leg swelling had not abated and new abdominal distention occurred. He called the primary care clinic and was instructed to seek evaluation at the emergency department of this hospital.
On evaluation, a review of systems was notable for fatigue, lethargy, decreased appetite, abdominal bloating, constipation, penile swelling, decreased libido, intolerance of cold temperatures, and ankle and knee pain in both legs that was worse when the patient was climbing stairs. There was no fever, shortness of breath, chest pain, or hematochezia.
Sixteen months before the current evaluation, the patient had been admitted to this hospital with pneumonia involving the right upper and middle lobes that was due to Mycoplasma pneumoniae. During that admission, he received diagnoses of diabetes and normocytic anemia. After discharge from the hospital, laboratory evaluation revealed a glycated hemoglobin level of 6.1% (reference range, 4.3 to 6.4). Metformin was prescribed, and follow-up evaluation was recommended; however, the patient had not returned to the primary care clinic before the current illness.
The patient had not started taking metformin until 3 weeks before the current evaluation; he took no other medications and had no known drug allergies. He lived with his wife and two children in an urban area of New England. He did not smoke tobacco or use illicit drugs. His mother had Parkinson's disease and dementia; he did not know the health of his father or paternal half-siblings.
On examination, the temperature was 36.6[degrees]C, the blood pressure 98/54 mm Hg, the heart rate 64 beats per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 27.3. The patient did not have jaundice, scleral icterus, or spider angiomas. He had jugular venous distention and an S3 gallop; there were no rales. The abdomen was distended, with dullness on percussion of the flanks; there was no hepatosplenomegaly. There was 2+ symmetric pitting edema in the lower legs up to the knees. Mild palmar erythema was present; there was no asterixis.
The blood glucose level was 402 mg per deciliter (22.3 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]); the glycated hemoglobin level was 11.6%. The platelet count was 82,000 per microliter (reference range, 150,000 to 400,000). Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Reece J. Goiffon: Radiography of the chest revealed new elevation of the right hemidiaphragm and atelectasis in the lower lobes. Ultrasonography with Doppler analysis of the abdomen revealed mild thickening of the gallbladder wall, coarsened liver echotexture, moderate ascites, and mild splenomegaly; the portal veins were patent. Duplex ultrasonography revealed nonocclusive deep-vein thrombosis of the right popliteal vein.
Dr. Wing: Paracentesis was performed with ultrasonographic guidance, and 50 ml of peritoneal fluid was drained. Results of peritoneal fluid analysis are shown in Table 1; cytologic examination of the fluid revealed no malignant cells. Electrocardiography revealed normal sinus rhythm with occasional premature atrial complexes, left axis deviation, and T-wave inversions in leads I and aVL. Insulin and enoxaparin were administered subcutaneously, and the patient was admitted to the hospital. A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old man was admitted to this hospital because of fatigue and swelling in both legs.
The patient had been well until 8 months before the current admission, when fatigue and lethargy developed. He thought the fatigue was associated with alcohol consumption and reduced his intake to 12 beers weekly; before this, he had consumed 24 beers weekly for 15 years. Three months before the current admission, the patient's weight had decreased by 9.1 kg. However, 3 weeks before this admission, the weight had increased by 9.6 kg and swelling developed in both legs. He thought the weight gain was related to diet changes, including consumption of pizza, pasta, and soup, during the coronavirus disease 2019 pandemic.
One week before the current admission, the patient was evaluated by his primary care physician. He was instructed to elevate his legs, wear compression stockings, and decrease dietary sodium to 2 g daily. On the day of the current admission, the leg swelling had not abated and new abdominal distention occurred. He called the primary care clinic and was instructed to seek evaluation at the emergency department of this hospital.
On evaluation, a review of systems was notable for fatigue, lethargy, decreased appetite, abdominal bloating, constipation, penile swelling, decreased libido, intolerance of cold temperatures, and ankle and knee pain in both legs that was worse when the patient was climbing stairs. There was no fever, shortness of breath, chest pain, or hematochezia.
Sixteen months before the current evaluation, the patient had been admitted to this hospital with pneumonia involving the right upper and middle lobes that was due to Mycoplasma pneumoniae. During that admission, he received diagnoses of diabetes and normocytic anemia. After discharge from the hospital, laboratory evaluation revealed a glycated hemoglobin level of 6.1% (reference range, 4.3 to 6.4). Metformin was prescribed, and follow-up evaluation was recommended; however, the patient had not returned to the primary care clinic before the current illness.
The patient had not started taking metformin until 3 weeks before the current evaluation; he took no other medications and had no known drug allergies. He lived with his wife and two children in an urban area of New England. He did not smoke tobacco or use illicit drugs. His mother had Parkinson's disease and dementia; he did not know the health of his father or paternal half-siblings.
On examination, the temperature was 36.6[degrees]C, the blood pressure 98/54 mm Hg, the heart rate 64 beats per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 27.3. The patient did not have jaundice, scleral icterus, or spider angiomas. He had jugular venous distention and an S3 gallop; there were no rales. The abdomen was distended, with dullness on percussion of the flanks; there was no hepatosplenomegaly. There was 2+ symmetric pitting edema in the lower legs up to the knees. Mild palmar erythema was present; there was no asterixis.
The blood glucose level was 402 mg per deciliter (22.3 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]); the glycated hemoglobin level was 11.6%. The platelet count was 82,000 per microliter (reference range, 150,000 to 400,000). Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Reece J. Goiffon: Radiography of the chest revealed new elevation of the right hemidiaphragm and atelectasis in the lower lobes. Ultrasonography with Doppler analysis of the abdomen revealed mild thickening of the gallbladder wall, coarsened liver echotexture, moderate ascites, and mild splenomegaly; the portal veins were patent. Duplex ultrasonography revealed nonocclusive deep-vein thrombosis of the right popliteal vein.
Dr. Wing: Paracentesis was performed with ultrasonographic guidance, and 50 ml of peritoneal fluid was drained. Results of peritoneal fluid analysis are shown in Table 1; cytologic examination of the fluid revealed no malignant cells. Electrocardiography revealed normal sinus rhythm with occasional premature atrial complexes, left axis deviation, and T-wave inversions in leads I and aVL. Insulin and enoxaparin were administered subcutaneously, and the patient was admitted to the hospital. A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with fatigue, lethargy, decreased appetite, abdominal bloating, constipation, penile swelling, decreased libido, intolerance of cold temperatures, and ankle and knee pain in both legs. He also has a history of heavy alcohol consumption. His physical examination reveals jugular venous distention, an S3 gallop, distended abdomen with dullness on percussion of the flanks, and 2+ symmetric pitting edema in the lower legs up to the knees. These symptoms and signs are suggestive of congestive heart failure. His lab results show a high blood glucose level and a high glycated hemoglobin level, indicating poorly controlled diabetes. The patient also has thrombocytopenia, which can be caused by liver disease. The ultrasound findings of coarsened liver echotexture, moderate ascites, and mild splenomegaly are consistent with cirrhosis, likely due to his history of heavy alcohol consumption. The presence of nonocclusive deep-vein thrombosis of the right popliteal vein could be a result of the liver disease, as the liver plays a crucial role in the production of clotting factors. The paracentesis results further support the diagnosis of cirrhosis with ascites.\n\nDiagnosis: Alcoholic cirrhosis with congestive heart failure.""
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        ""content"": ""The patient presents with fatigue, lethargy, decreased appetite, abdominal bloating, constipation, penile swelling, decreased libido, intolerance of cold temperatures, and ankle and knee pain in both legs. He also has a history of diabetes and normocytic anemia. His physical examination reveals jugular venous distention, an S3 gallop, distended abdomen with dullness on percussion of the flanks, and 2+ symmetric pitting edema in the lower legs up to the knees. These symptoms suggest fluid overload, possibly due to heart failure. However, his lab results show a high blood glucose level and a glycated hemoglobin level of 11.6%, indicating poorly controlled diabetes. His platelet count is also low. The ultrasound reveals coarsened liver echotexture, moderate ascites, and mild splenomegaly, which are signs of liver disease. The presence of nonocclusive deep-vein thrombosis of the right popliteal vein also suggests a hypercoagulable state, which can be associated with liver disease. The paracentesis results show a high serum-ascites albumin gradient (SAAG), which is indicative of portal hypertension, commonly seen in cirrhosis. Therefore, the patient's symptoms, along with the lab and imaging results, suggest cirrhosis, possibly due to alcoholic liver disease given his history of heavy alcohol consumption.\n\nDiagnosis: Alcoholic Cirrhosis.""
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        ""content"": ""The patient is a 48-year-old man presenting with fatigue, lethargy, weight loss followed by weight gain, bilateral leg swelling, abdominal distention, penile swelling, decreased libido, intolerance of cold temperatures, and joint pain. He has a history of heavy alcohol consumption, diabetes, and normocytic anemia. On examination, he has jugular venous distention, an S3 gallop, abdominal distention with dullness on percussion of the flanks, and 2+ symmetric pitting edema in the lower legs up to the knees. His blood glucose level is elevated, and he has thrombocytopenia. Imaging reveals new elevation of the right hemidiaphragm, atelectasis in the lower lobes, coarsened liver echotexture, moderate ascites, mild splenomegaly, and nonocclusive deep-vein thrombosis of the right popliteal vein. \n\nThe differential diagnosis for this patient includes alcoholic liver disease, congestive heart failure, nephrotic syndrome, and hypothyroidism. The patient's history of heavy alcohol consumption, coarsened liver echotexture, moderate ascites, and mild splenomegaly on imaging, and low platelet count are suggestive of alcoholic liver disease. The presence of an S3 gallop and jugular venous distention could suggest congestive heart failure, but the patient does not have shortness of breath or chest pain. Nephrotic syndrome could cause edema and weight gain, but the patient does not have proteinuria. Hypothyroidism could explain the patient's fatigue, lethargy, weight gain, and cold intolerance, but the patient does not have other symptoms such as dry skin or hair loss.\n\nGiven the patient's history of heavy alcohol consumption, the presence of ascites and splenomegaly on imaging, and the low platelet count, the most likely diagnosis is alcoholic liver disease.\n\nDiagnosis: Alcoholic liver disease.""
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10.1056/NEJMcpc2107345,"Case 24-2021: A 63-Year-Old Woman with Fever, Sore Throat, and Confusion","Hemoglobin (g/dl)   14.2
Hematocrit (%)   42.2
White-cell count (per μl)   3700
Differential count (per μl)
Neutrophils   2290
Lymphocytes   1320
Monocytes   60
Platelet count (per μl)   230,000
Sodium (mmol/liter)   131
Potassium (mmol/liter)   4.8
Chloride (mmol/liter)   93
Glucose (mg/dl)   127
Creatinine (mg/dl)   0.92
Urea nitrogen (mg/dl)   8
Aspartate aminotransferase (U/liter)   280
Alanine aminotransferase (U/liter)   235
Alkaline phosphatase (U/liter)   205
Total bilirubin (mg/dl)  0.3
Direct bilirubin (mg/dl) 0.  <0.2
Albumin (g/dl)   4.5
Globulin (g/dl)   3.0
Lactate dehydrogenase (U/liter) 11 10 466                                                                    HIV-1 and HIV-2 antigen and antibody assay Reactive
HIV-1 and HIV-2 lateral flow immunochromatographic assay Negative for HIV-1 antibodies;
indeterminate for HIV-2 antibodies
Quantitative HIV-1 nucleic acid assay (RNA copies/ml) 8,420,000
Total lymphocyte count (no. per μl) 3745
CD4+ T-cell count
Absolute (no. per μl) 446
Relative (% of total lymphocyte count) 11.9",Acute human immunodeficiency virus type 1 infection,Acute human immunodeficiency virus type 1 infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 63-year-old woman was admitted to this hospital because of fever, headache, sore throat, and confusion.
The patient had been well until 2 weeks before this admission, when fever, chills, myalgias, and headache developed. She also had sore throat, odynophagia, and the feeling of a ""lump"" in the neck. The patient was concerned that she had coronavirus disease 2019 (Covid-19) and sought evaluation at an urgent care clinic of another hospital. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative, and she was instructed to quarantine at home.
Five days before this admission, the patient returned to the clinic of the other hospital because of persistent symptoms, including daily fevers. The temperature was 37.2[degrees]C, and the remainder of the physical examination was reportedly normal. Testing of another nasopharyngeal swab for SARS-CoV-2 RNA was negative, as was testing of an oropharyngeal swab for the rapid detection of streptococcal antigen.
On the day of admission, the patient's sister visited the patient and noticed that she had difficulty with word finding and performing basic tasks at home. Emergency medical services were called, and the patient was transported to the emergency department of this hospital.
On evaluation, the patient reported fevers, chills, myalgias, fatigue, generalized weakness, headaches, sore throat, and odynophagia. She acknowledged that she had mild confusion and ""mental slowness"" of 2 weeks' duration. A review of systems was notable for a lump in the neck, poor appetite, unintentional weight loss of 3 kg in the past 2 weeks, and anosmia for the past year, with onset before the beginning of the Covid-19 pandemic. There was no neck stiffness, photophobia, cough, dyspnea, abdominal pain, diarrhea, or dysuria.
The patient had hypertension for which she took amlodipine and lisinopril; there were no known drug allergies. She was born in South America and had immigrated to the United States two decades earlier. She lived in an urban area of New England with her mother and son. Her son had a brain injury and was seen by visiting nurses daily; one nurse had had a positive SARS-CoV-2 test 4 days before this evaluation. There were no other sick contacts. The patient worked in management and enjoyed gardening as a hobby. She had no recent insect bites or travel. Although she had not been sexually active for several years, she had had an episode of unprotected sexual intercourse with a new male partner 3 weeks before this evaluation. She smoked four cigarettes daily and had done so for 40 years. She did not drink alcohol or use illicit drugs. Her mother had Alzheimer's disease.
The temperature was 38.9[degrees]C, the blood pressure 160/80 mm Hg, the pulse 96 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 29.9. The patient appeared fatigued and was alert and oriented. She was unable to perform simple calculations, to list the days of the week in reverse order, or to follow two-step commands. The mucous membranes were dry, and a small nontender lymph node was palpable in the posterior neck on the left side. The white-cell count was 3700 per microliter (reference range, 4500 to 11,000); the aspartate aminotransferase level was 280 U per liter (reference range, 9 to 32) and the alanine aminotransferase level 235 U per liter (reference range, 7 to 33). Additional laboratory test results are shown in Table 1. Urinalysis revealed the presence of ketones, nitrites, and protein; there were fewer than 10 white cells per high-power field (reference range,  ). Testing of a third nasopharyngeal swab for SARS-CoV-2 RNA was negative, and blood specimens were obtained for culture.	
Table 1 
Dr. William A. Mehan: A radiograph of the chest was normal. Ultrasonography of the abdomen showed gallbladder sludge. Computed tomography (CT) of the abdomen, performed after the intravenous administration of contrast material, showed prominent gastrohepatic, periportal, periaortic, and inguinal lymph nodes, the largest measuring 1.4 cm in diameter.
CT of the head, performed without the intravenous administration of contrast material, showed mild scattered hypodensities in the periventricular and subcortical white matter of the cerebral hemispheres. Magnetic resonance imaging (MRI) of the head, performed before and after the intravenous administration of contrast material, was notable for multifocal patchy hyperintensities throughout the juxtacortical and deep white matter of the cerebral hemispheres on fluid-attenuated inversion recovery images, without corresponding restricted diffusion or abnormal enhancement (Figure 1). The findings were unchanged from MRI findings obtained 3 months before presentation.	
Figure 1
Dr. Ni: Empirical treatment with intravenous ceftriaxone and acyclovir was started, and the patient was admitted to the hospital.
A lumbar puncture was performed. The opening pressure was 24 cm of water; the cerebrospinal fluid (CSF) was clear and colorless. On CSF analysis, the total protein level was 201 mg per deciliter (reference range, 5 to 55) and the glucose level 43 mg per deciliter (2.4 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]). There were 73 white cells per microliter (reference range, 0 to 5), of which 65% were lymphocytes, 29% plasma cells, and 6% monocytes. Gram's staining showed abundant mononuclear cells and no organisms. The intravenous administration of ceftriaxone and acyclovir was stopped.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 63-year-old woman was admitted to this hospital because of fever, headache, sore throat, and confusion.
The patient had been well until 2 weeks before this admission, when fever, chills, myalgias, and headache developed. She also had sore throat, odynophagia, and the feeling of a ""lump"" in the neck. The patient was concerned that she had coronavirus disease 2019 (Covid-19) and sought evaluation at an urgent care clinic of another hospital. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative, and she was instructed to quarantine at home.
Five days before this admission, the patient returned to the clinic of the other hospital because of persistent symptoms, including daily fevers. The temperature was 37.2[degrees]C, and the remainder of the physical examination was reportedly normal. Testing of another nasopharyngeal swab for SARS-CoV-2 RNA was negative, as was testing of an oropharyngeal swab for the rapid detection of streptococcal antigen.
On the day of admission, the patient's sister visited the patient and noticed that she had difficulty with word finding and performing basic tasks at home. Emergency medical services were called, and the patient was transported to the emergency department of this hospital.
On evaluation, the patient reported fevers, chills, myalgias, fatigue, generalized weakness, headaches, sore throat, and odynophagia. She acknowledged that she had mild confusion and ""mental slowness"" of 2 weeks' duration. A review of systems was notable for a lump in the neck, poor appetite, unintentional weight loss of 3 kg in the past 2 weeks, and anosmia for the past year, with onset before the beginning of the Covid-19 pandemic. There was no neck stiffness, photophobia, cough, dyspnea, abdominal pain, diarrhea, or dysuria.
The patient had hypertension for which she took amlodipine and lisinopril; there were no known drug allergies. She was born in South America and had immigrated to the United States two decades earlier. She lived in an urban area of New England with her mother and son. Her son had a brain injury and was seen by visiting nurses daily; one nurse had had a positive SARS-CoV-2 test 4 days before this evaluation. There were no other sick contacts. The patient worked in management and enjoyed gardening as a hobby. She had no recent insect bites or travel. Although she had not been sexually active for several years, she had had an episode of unprotected sexual intercourse with a new male partner 3 weeks before this evaluation. She smoked four cigarettes daily and had done so for 40 years. She did not drink alcohol or use illicit drugs. Her mother had Alzheimer's disease.
The temperature was 38.9[degrees]C, the blood pressure 160/80 mm Hg, the pulse 96 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 29.9. The patient appeared fatigued and was alert and oriented. She was unable to perform simple calculations, to list the days of the week in reverse order, or to follow two-step commands. The mucous membranes were dry, and a small nontender lymph node was palpable in the posterior neck on the left side. The white-cell count was 3700 per microliter (reference range, 4500 to 11,000); the aspartate aminotransferase level was 280 U per liter (reference range, 9 to 32) and the alanine aminotransferase level 235 U per liter (reference range, 7 to 33). Additional laboratory test results are shown in Table 1. Urinalysis revealed the presence of ketones, nitrites, and protein; there were fewer than 10 white cells per high-power field (reference range,  ). Testing of a third nasopharyngeal swab for SARS-CoV-2 RNA was negative, and blood specimens were obtained for culture.	
Table 1 
Dr. William A. Mehan: A radiograph of the chest was normal. Ultrasonography of the abdomen showed gallbladder sludge. Computed tomography (CT) of the abdomen, performed after the intravenous administration of contrast material, showed prominent gastrohepatic, periportal, periaortic, and inguinal lymph nodes, the largest measuring 1.4 cm in diameter.
CT of the head, performed without the intravenous administration of contrast material, showed mild scattered hypodensities in the periventricular and subcortical white matter of the cerebral hemispheres. Magnetic resonance imaging (MRI) of the head, performed before and after the intravenous administration of contrast material, was notable for multifocal patchy hyperintensities throughout the juxtacortical and deep white matter of the cerebral hemispheres on fluid-attenuated inversion recovery images, without corresponding restricted diffusion or abnormal enhancement (Figure 1). The findings were unchanged from MRI findings obtained 3 months before presentation.	
Figure 1
Dr. Ni: Empirical treatment with intravenous ceftriaxone and acyclovir was started, and the patient was admitted to the hospital.
A lumbar puncture was performed. The opening pressure was 24 cm of water; the cerebrospinal fluid (CSF) was clear and colorless. On CSF analysis, the total protein level was 201 mg per deciliter (reference range, 5 to 55) and the glucose level 43 mg per deciliter (2.4 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]). There were 73 white cells per microliter (reference range, 0 to 5), of which 65% were lymphocytes, 29% plasma cells, and 6% monocytes. Gram's staining showed abundant mononuclear cells and no organisms. The intravenous administration of ceftriaxone and acyclovir was stopped.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Neurosyphilis. The patient's symptoms of fever, headache, sore throat, and confusion, along with her history of unprotected sexual intercourse, suggest a sexually transmitted infection. The presence of lymphadenopathy and abnormal liver function tests further support this. The patient's cognitive impairment and the findings on her cerebrospinal fluid analysis, including lymphocytic pleocytosis and elevated protein, are consistent with neurosyphilis. The negative tests for SARS-CoV-2 rule out COVID-19.""
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        ""content"": ""The patient's symptoms of fever, headache, sore throat, and confusion, along with the presence of lymphadenopathy, suggest an infectious process. The patient's history of recent unprotected sexual intercourse and the presence of lymphadenopathy also raise the possibility of a sexually transmitted infection. The patient's elevated liver enzymes and the presence of mononuclear cells in the cerebrospinal fluid further support an infectious process. The negative tests for SARS-CoV-2 and streptococcal antigen, along with the lack of response to ceftriaxone and acyclovir, suggest that the cause of the patient's symptoms is not a common respiratory or bacterial infection. The presence of plasma cells in the cerebrospinal fluid is unusual and suggests a chronic or atypical infection. Given these findings, a diagnosis of neurosyphilis is likely.\n\nDiagnosis: Neurosyphilis.""
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        ""content"": ""The patient is a 63-year-old woman presenting with fever, headache, sore throat, and confusion. She also reports a lump in the neck, unintentional weight loss, and anosmia. The differential diagnosis for this patient includes bacterial or viral meningitis, encephalitis, brain abscess, neurosyphilis, and lymphoma. The patient's CSF analysis shows elevated protein and white cells, which is suggestive of an infection or inflammation in the central nervous system. However, Gram's staining showed no organisms, making bacterial meningitis less likely. The patient's MRI findings of multifocal patchy hyperintensities in the white matter are not typical for a brain abscess, making this diagnosis less likely. The patient's history of unprotected sexual intercourse raises the possibility of neurosyphilis, but this is less likely given the absence of other typical symptoms such as vision changes or motor deficits. The patient's lymphadenopathy and unintentional weight loss raise the possibility of lymphoma, but this is less likely given the absence of other typical symptoms such as night sweats. The patient's symptoms, CSF findings, and MRI findings are most consistent with encephalitis, which can be caused by a variety of viral infections. Given the patient's recent exposure to a nurse with a positive SARS-CoV-2 test, it is possible that she has encephalitis due to SARS-CoV-2, despite her negative nasopharyngeal swabs. \n\nDiagnosis: Encephalitis, possibly due to SARS-CoV-2.""
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10.1056/NEJMcpc2103461,Case 23-2021: A 41-Year-Old Woman with Bloody Stools and Thrombocytopenia,"Platelet count (per μl)   129,000 0
White-cell count (per μl)   7500 8490
Differential count (per μl)
Neutrophils   6428 6920
Lymphocytes   255 1120
Monocytes 20–120 803 300
Eosinophils   8 0
Basophils  00 8 80
Hemoglobin (g/dl)   11.0 6.0
Hematocrit (%)  32.9 19.6
Mean corpuscular volume (fl)   — 74.5
Mean corpuscular hemoglobin (pg) 26. 4.0 — 22.8
Red-cell distribution width (%)   — 14.8
Reticulocytes (%) 0.7–2.5 — 1.3
Alanine aminotransferase (U/liter) 0–41 — 80
Aspartate aminotransferase (U/liter) 10–50 — 104
Albumin (g/dl) 3.5–5.2 — 2.5
Total bilirubin (mg/dl)  — 0.5
Lactate dehydrogenase (U/liter) 11 10 — 465
Haptoglobin (mg/dl) 3 00 — 38
Prothrombin time (sec)   — 13.9
International normalized ratio   — 1.1
Activated partial-thromboplastin time (sec) 22. 6.0 — 33.2
Fibrinogen (mg/dl) 15 0 — 288
d-Dimer (ng/ml)   — 1650
Creatinine (mg/dl)   0.86 0.85
Urea nitrogen (mg/dl)   11 12
Potassium (mmol/liter)   3.7 4.2
Sodium (mmol/liter)   135 132
Glucose (mg/dl)   196 234
Urine
Bilirubin Negative — Negative
Urobilinogen Negative — Negative
Blood Negative — 2+
Glucose Negative — 1+
Ketones Negative — 1+
Leukocyte esterase Negative — Negative
Nitrites Negative — Negative",Cytomegalovirus-induced immune thrombocytopenia.,"Primary cytomegalovirus infection associated with proctocolitis in the context of belatacept immunosuppression, complicated by gastrointestinal bleeding due to secondary immune thrombocytopenia.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 41-year-old woman who had undergone renal transplantation was admitted to this hospital because of bloody stools and thrombocytopenia.
The patient had been in her usual state of health until 3 weeks before this admission, when mild rectal discomfort and nonbloody diarrhea developed. The episodes of diarrhea occurred several times a day and were not associated with fever, chills, abdominal pain, nausea, or vomiting.
Two weeks before this admission, the patient sought evaluation at this hospital. The abdominal and rectal examinations were normal. The hemoglobin level was 11.0 g per deciliter (reference range, 14.0 to 18.0) and the platelet count 129,000 per microliter (reference range, 150,000 to 450,000). Stool cultures and tests of the stool for Clostridioides difficile antigen and toxin and Shiga toxin were negative, as was examination of the stool for ova and parasites. Other laboratory test results are shown in Table 1. Treatment with docusate was stopped, treatment with topical rectal hydrocortisone cream was started, and a recommendation was made to increase the amount of fiber in the diet. During the next week, the episodes of diarrhea decreased in frequency to once a day; however, the rectal pain persisted.	
Table 1 
One week before this admission, the patient was evaluated by her primary care physician because the rectal pain had worsened; she was unable to sit down, and new tenesmus was present. A rectal examination revealed mild tenderness and thin yellow-brown liquid stool, with no evidence of blood or an external anal injury. A radiograph of the abdomen was normal. Docusate, senna, and topical lidocaine jelly were prescribed.
Three days before this admission, bowel movements with tarry black and loose maroon stools and dark clots began to occur multiple times a day. When the episodes increased in frequency to every hour and there was bright-red blood per rectum, the patient presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported severe rectal pain and burning, as well as fatigue, dizziness, and weakness. She did not report fever, chills, abdominal pain, hematemesis, hemoptysis, epistaxis, rash, bruising, hematuria, or menorrhagia.
The patient was congenitally deaf. She had received a diagnosis of kidney disease 12 years earlier, when proteinuria and hypertension developed during pregnancy and did not resolve postpartum. Pathological examination of a renal biopsy specimen had reportedly revealed focal segmental glomerulosclerosis. The patient was presumed to have Alport's syndrome; no genetic testing had been performed.
Ten years before the current evaluation, the patient had discontinued all prescribed medications, including prednisone and labetalol, without talking to her doctors; 3 years later, she presented to this hospital with dyspnea on exertion and end-stage renal failure. Hemodialysis was started and continued until a deceased-donor renal transplantation was performed 6 months before the current evaluation.
Routine pretransplantation serologic testing of the patient revealed IgG antibodies to Epstein-Barr virus (EBV) and no antibodies to cytomegalovirus (CMV). Serologic testing of the donor also revealed IgG antibodies to EBV and no antibodies to CMV. Induction immunosuppressive therapy with antithymocyte globulin, belatacept, prednisone, and everolimus was initiated; famciclovir was administered for 3 months after transplantation. Treatment with prednisone was stopped 2 months after transplantation, when diabetes developed.
At the time of the current evaluation, medications included aspirin, linagliptin, trimethoprim-sulfamethoxazole, and omeprazole, as well as cholecalciferol, docusate, senna, topical hydrocortisone cream, and topical lidocaine jelly. The dose of everolimus had been decreased 1 month before this evaluation; belatacept had last been infused 2 weeks earlier. There were no known drug allergies.
The patient lived with her male partner and young son in an urban area of New England. She had not traveled recently. She had previously worked part-time as a teacher. There had been no exposure to animals other than two pet dogs. She had never smoked tobacco and did not drink alcohol. Her sister was deaf and had a history of renal failure that had led to renal transplantation. Her father had a history of diabetes and renal failure that required hemodialysis.
On examination, the temperature was 37.2[degrees]C, the blood pressure 85/46 mm Hg, the pulse 130 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She appeared pale and unwell. There was no jaundice or lymphadenopathy. There were palatal petechiae and sublingual ecchymoses, but there was no bleeding from the gums or nose. There was a healed surgical incision in the right lower abdomen and no tenderness over the renal allograft. A rectal examination revealed tenderness and dark blood with clots.
The hemoglobin level was 6.0 g per deciliter and the platelet count 0 per microliter. A peripheral-blood smear showed red cells that were generally normal in size and morphology, with few hypochromic cells and rare pencil cells; there were no schistocytes or platelets. A direct antiglobulin test was negative. Blood cultures were obtained. Other laboratory test results are shown in Table 1.
Dr. Onofrio A. Catalano: Computed tomography (CT) of the abdomen and pelvis, performed without the administration of intravenous contrast material, revealed no bowel-wall thickening or distention. The spleen and liver were normal in size. The renal allograft was visible in the right lower quadrant (Figure 1). The transplanted kidney was enlarged and surrounded by extensive perinephric fat stranding. A small amount of free fluid was also present. There was moderate hydroureteronephrosis that extended up to the ureterovesical anastomosis. The renal collecting system, pelvis, and ureter contained spontaneously hyperdense material that was suggestive of blood breakdown products. No obstructing calculi were seen.	
Figure 1 
Dr. Roberts: Intravenous fluids were administered, and the blood pressure increased to 97/53 mm Hg. The patient was admitted to the hospital, and treatment with everolimus and trimethoprim-sulfamethoxazole was stopped. During the next 24 hours, 4 units of packed red cells and 5 units of pooled platelets were transfused. On the second hospital day, the hemoglobin level was 11.0 g per deciliter and the platelet count 4 per microliter.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 41-year-old woman who had undergone renal transplantation was admitted to this hospital because of bloody stools and thrombocytopenia.
The patient had been in her usual state of health until 3 weeks before this admission, when mild rectal discomfort and nonbloody diarrhea developed. The episodes of diarrhea occurred several times a day and were not associated with fever, chills, abdominal pain, nausea, or vomiting.
Two weeks before this admission, the patient sought evaluation at this hospital. The abdominal and rectal examinations were normal. The hemoglobin level was 11.0 g per deciliter (reference range, 14.0 to 18.0) and the platelet count 129,000 per microliter (reference range, 150,000 to 450,000). Stool cultures and tests of the stool for Clostridioides difficile antigen and toxin and Shiga toxin were negative, as was examination of the stool for ova and parasites. Other laboratory test results are shown in Table 1. Treatment with docusate was stopped, treatment with topical rectal hydrocortisone cream was started, and a recommendation was made to increase the amount of fiber in the diet. During the next week, the episodes of diarrhea decreased in frequency to once a day; however, the rectal pain persisted.	
Table 1 
One week before this admission, the patient was evaluated by her primary care physician because the rectal pain had worsened; she was unable to sit down, and new tenesmus was present. A rectal examination revealed mild tenderness and thin yellow-brown liquid stool, with no evidence of blood or an external anal injury. A radiograph of the abdomen was normal. Docusate, senna, and topical lidocaine jelly were prescribed.
Three days before this admission, bowel movements with tarry black and loose maroon stools and dark clots began to occur multiple times a day. When the episodes increased in frequency to every hour and there was bright-red blood per rectum, the patient presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported severe rectal pain and burning, as well as fatigue, dizziness, and weakness. She did not report fever, chills, abdominal pain, hematemesis, hemoptysis, epistaxis, rash, bruising, hematuria, or menorrhagia.
The patient was congenitally deaf. She had received a diagnosis of kidney disease 12 years earlier, when proteinuria and hypertension developed during pregnancy and did not resolve postpartum. Pathological examination of a renal biopsy specimen had reportedly revealed focal segmental glomerulosclerosis. The patient was presumed to have Alport's syndrome; no genetic testing had been performed.
Ten years before the current evaluation, the patient had discontinued all prescribed medications, including prednisone and labetalol, without talking to her doctors; 3 years later, she presented to this hospital with dyspnea on exertion and end-stage renal failure. Hemodialysis was started and continued until a deceased-donor renal transplantation was performed 6 months before the current evaluation.
Routine pretransplantation serologic testing of the patient revealed IgG antibodies to Epstein-Barr virus (EBV) and no antibodies to cytomegalovirus (CMV). Serologic testing of the donor also revealed IgG antibodies to EBV and no antibodies to CMV. Induction immunosuppressive therapy with antithymocyte globulin, belatacept, prednisone, and everolimus was initiated; famciclovir was administered for 3 months after transplantation. Treatment with prednisone was stopped 2 months after transplantation, when diabetes developed.
At the time of the current evaluation, medications included aspirin, linagliptin, trimethoprim-sulfamethoxazole, and omeprazole, as well as cholecalciferol, docusate, senna, topical hydrocortisone cream, and topical lidocaine jelly. The dose of everolimus had been decreased 1 month before this evaluation; belatacept had last been infused 2 weeks earlier. There were no known drug allergies.
The patient lived with her male partner and young son in an urban area of New England. She had not traveled recently. She had previously worked part-time as a teacher. There had been no exposure to animals other than two pet dogs. She had never smoked tobacco and did not drink alcohol. Her sister was deaf and had a history of renal failure that had led to renal transplantation. Her father had a history of diabetes and renal failure that required hemodialysis.
On examination, the temperature was 37.2[degrees]C, the blood pressure 85/46 mm Hg, the pulse 130 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She appeared pale and unwell. There was no jaundice or lymphadenopathy. There were palatal petechiae and sublingual ecchymoses, but there was no bleeding from the gums or nose. There was a healed surgical incision in the right lower abdomen and no tenderness over the renal allograft. A rectal examination revealed tenderness and dark blood with clots.
The hemoglobin level was 6.0 g per deciliter and the platelet count 0 per microliter. A peripheral-blood smear showed red cells that were generally normal in size and morphology, with few hypochromic cells and rare pencil cells; there were no schistocytes or platelets. A direct antiglobulin test was negative. Blood cultures were obtained. Other laboratory test results are shown in Table 1.
Dr. Onofrio A. Catalano: Computed tomography (CT) of the abdomen and pelvis, performed without the administration of intravenous contrast material, revealed no bowel-wall thickening or distention. The spleen and liver were normal in size. The renal allograft was visible in the right lower quadrant (Figure 1). The transplanted kidney was enlarged and surrounded by extensive perinephric fat stranding. A small amount of free fluid was also present. There was moderate hydroureteronephrosis that extended up to the ureterovesical anastomosis. The renal collecting system, pelvis, and ureter contained spontaneously hyperdense material that was suggestive of blood breakdown products. No obstructing calculi were seen.	
Figure 1 
Dr. Roberts: Intravenous fluids were administered, and the blood pressure increased to 97/53 mm Hg. The patient was admitted to the hospital, and treatment with everolimus and trimethoprim-sulfamethoxazole was stopped. During the next 24 hours, 4 units of packed red cells and 5 units of pooled platelets were transfused. On the second hospital day, the hemoglobin level was 11.0 g per deciliter and the platelet count 4 per microliter.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Thrombotic Thrombocytopenic Purpura (TTP). The patient's symptoms of bloody stools, thrombocytopenia, and anemia, along with the absence of platelets in the peripheral blood smear, suggest a diagnosis of TTP. This condition is characterized by the formation of small blood clots throughout the body, leading to low platelet counts and often resulting in anemia. The patient's recent renal transplantation and immunosuppressive therapy could have triggered the onset of TTP.""
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        ""content"": ""The patient is a 41-year-old woman who had undergone renal transplantation and is now presenting with bloody stools and thrombocytopenia. She has a history of kidney disease and was presumed to have Alport's syndrome. She is on immunosuppressive therapy post-transplantation. Her symptoms started with mild rectal discomfort and nonbloody diarrhea, which then progressed to severe rectal pain and bloody stools. Her platelet count is extremely low, and she has palatal petechiae and sublingual ecchymoses, which are signs of bleeding. Her renal allograft is enlarged and surrounded by extensive perinephric fat stranding, and there is moderate hydroureteronephrosis. These findings suggest a post-transplant complication. Given her symptoms and the fact that she is on immunosuppressive therapy, the most likely diagnosis is post-transplant lymphoproliferative disorder (PTLD). PTLD is a complication of solid organ transplantation and is associated with Epstein-Barr virus (EBV), which the patient has IgG antibodies to. PTLD can present with a variety of symptoms, including gastrointestinal symptoms like the patient's, and can cause cytopenias like the patient's thrombocytopenia.\n\nDiagnosis: Post-transplant lymphoproliferative disorder (PTLD)""
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        ""content"": ""The patient is a 41-year-old woman with a history of renal transplantation who presents with bloody stools and thrombocytopenia. The differential diagnosis for this patient includes drug-induced thrombocytopenia, post-transplant lymphoproliferative disorder (PTLD), thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and disseminated intravascular coagulation (DIC). \n\nThe patient's history of renal transplantation and immunosuppressive therapy increases her risk for PTLD. However, the absence of lymphadenopathy and the normal size of the spleen and liver on CT scan make this diagnosis less likely. \n\nDrug-induced thrombocytopenia is also a possibility given the patient's extensive medication list. However, the sudden onset of severe thrombocytopenia and the presence of bloody stools suggest a more acute process. \n\nTTP and HUS are characterized by thrombocytopenia and microangiopathic hemolytic anemia. However, the patient's peripheral blood smear does not show schistocytes, which are typically seen in these conditions. \n\nDIC is characterized by widespread activation of the coagulation cascade, leading to thrombocytopenia and bleeding. However, the patient's coagulation studies are not provided, making it difficult to assess for this condition. \n\nGiven the patient's history of renal transplantation, immunosuppressive therapy, and the presence of bloody stools and severe thrombocytopenia, the most likely diagnosis is PTLD, specifically a form of PTLD that affects the gastrointestinal tract.\n\nDiagnosis: Post-transplant lymphoproliferative disorder (PTLD) affecting the gastrointestinal tract.""
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10.1056/NEJMcpc2103460,"Case 22-2021: A 64-Year-Old Woman with Cognitive Impairment, Headache, and Memory Loss","Thyrotropin (μIU/ml) — — 0.40 to 5.00 8.65
Free thyroxine (ng/dl) — — 0.9 to 1.8 1.4
Antithyroid peroxidase antibodies (IU/ml) — — <35.0 32.4
IgG (mg/dl) 586 to 1602 946 767 to 1590 814
Albumin (g/dl) 3.8 to 4.8 5.2 3.2 to 4.8 4.24
Interferon-gamma release assay Negative Negative — —
West Nile virus IgG and IgM Negative Negative — —
Q fever antibodies Negative Negative — —
Lyme disease antibodies Negative Negative Negative Negative
Brucella IgG and IgM — — Negative Negative
Anaplasma, PCR assay — — Negative Negative
Babesia, thick and thin smear — — Negative Negative
Urine
Histoplasma antigen — — Negative Negative
Cerebrospinal fluid
Red-cell count (per μl) 0 35 0 to 5 53
White-cell count (per μl) 0 to 5 46 0 to 5 28
Differential count (%)
Lymphocytes 40 to 80 99 0 to 100 85
Neutrophils 0 to 7 1 0 1
Monocytes 15 to 45 0 0 to 100 14
Protein (mg/dl) 13 to 40 221 5 to 55 280
Glucose (mg/dl)‡ 30 to 70 58 50 to 75 58
Gram’s stain — No bacteria seen — No bacteria seen
Xanthochromia — — — Present
Oligoclonal bands — Not seen — Not seen
IgG (mg/dl) 0 to 8.6 28.1 ≤8.1 34.6
IgG index 0 to 0.7 5.2 ≤0.85 1.05
IgG synthesis rate −9.9 to 3.3 per day 75.9 ≤12 per day 100.43
Albumin (mg/dl) 11 to 48 155 ≤27.0 172.0
Albumin index 0 to 8 30 ≤0.40 0.19
Herpes simplex viruses 1 and 2 DNA Negative Negative Negative Negative
West Nile virus RNA — — Negative Negative
Varicella–zoster virus, PCR assay — — Negative Negative
VDRL test — — Negative Negative
Lyme disease
IgG — p93, p28, p23 — —
IgM — p39 — —
Listeria antibodies — — <1:1 <1:1                                                                                                                       Histoplasma antibodies — — Negative Negative
Enterovirus RNA — — Negative Negative
Epstein–Barr virus DNA — — Negative Negative
Cryptococcal antigen — — Negative Negative
Arbovirus antibodies ‚Äö√Ñ√Æ ‚Äö√Ñ√Æ Negative Negative",Cerebral amyloid angiopathy‚Äö√Ñ√¨related inflammation.,Cerebral amyloid angiopathy–related inflammation.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old woman was admitted to this hospital with cognitive impairment, headache, and memory loss.
The patient had been well until 6 weeks before admission, when respiratory symptoms developed. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative. At around the same time, coworkers observed a decline in the patient's performance at work. The patient noticed that she was having difficulty operating computers and was forgetting her personal passwords.
The patient was evaluated at another hospital. Although she reported recent confusion and changes in cognitive performance, the examination at that time - including a neurologic examination with assessment of orientation, speech, and memory recall after 5 and 20 minutes - was unremarkable. The patient was referred for an outpatient neurologic evaluation.
One week later (5 weeks before admission), severe headache developed suddenly, along with blurred vision, dizziness, and nausea. After the administration of ondansetron, the blurred vision, dizziness, and nausea resolved; after the administration of nonsteroidal antiinflammatory drugs, the headache became less severe, with mild pain and intermittent episodes of more severe pain.
Three weeks before admission, the patient was seen in a neurology clinic affiliated with the other hospital. She had difficulty recalling the history of her symptoms. On examination, she was oriented to place and person only and was unable to perform serial sevens calculations or to spell ""world"" backward. The remainder of the examination was unremarkable. The complete blood count with differential count and test results for liver and kidney function were normal, as were blood levels of electrolytes, glucose, thiamine, and cobalamin. Tests for syphilis and human immunodeficiency virus infection were negative; other laboratory test results are shown in Table 1. An electroencephalogram (EEG) showed no distinct epileptiform activity. Topiramate was prescribed for a working diagnosis of complex migraine. Imaging studies were obtained.	
Table 1 
Dr. R. Gilberto Gonzalez: Magnetic resonance imaging (MRI) of the head was performed. T2-weighted fluid-attenuated inversion recovery (FLAIR) images showed diffusely scattered hyperintensities in the periventricular, subcortical, and deep white matter and leptomeningeal enhancement. In addition, there was evidence of frontal superficial siderosis and a few scattered microhemorrhages.
Dr. Manzano: Lumbar puncture was also performed. On cerebrospinal fluid (CSF) analysis, the white-cell count was 46 per microliter (reference range, 0 to 5), with a lymphocyte count of 99% (reference range, 40 to 80), the red-cell count was 35 per microliter (reference value, 0), and the protein level was 221 mg per deciliter (reference range, 13 to 40); other laboratory test results are shown in Table 1. Cultures of the CSF were negative. The administration of topiramate was stopped; treatment with oral doxycycline was started but then was stopped after 5 days, when results of a test for Borrelia burgdorferi were interpreted as negative.
Over the next 3 weeks, intermittent headache persisted and cognitive impairment worsened. The patient presented to the emergency department of this hospital. She was unable to provide a history. According to the patient's husband, the patient had stopped working and was no longer able to effectively care for herself, requiring assistance with daily activities such as bathing, dressing, and eating. She had difficulty planning and was unable to put on clothes in the correct sequence or to turn on the shower. Memory impairment persisted, conversation was tangential, and visual hallucinations frequently occurred. The patient had lost 6.8 kg in the past month. There was no fever, rash, or joint pain.
The patient had a history of poliomyelitis in childhood, with residual mild weakness in the left leg; vitamin B12 deficiency, which had been corrected; and hypothyroidism. Medications included atorvastatin, levothyroxine, sertraline, vitamin B12, and cholecalciferol. She had a known allergy to amoxicillin-clavulanate with an unknown reaction. She was a former smoker with a 40 pack-year history, and she had consumed four alcoholic beverages per week before the onset of the current illness. The patient worked in a health care clinic and lived with her husband in a suburban area of New England. She had not traveled outside the United States. She was an avid gardener; she had a dog but no other animal exposures. Her father had received a diagnosis of Alzheimer's disease at 62 years of age.
On examination, the patient was alert and interactive. The temperature was 36.7[degrees]C, the blood pressure 105/51 mm Hg, the heart rate 56 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while she was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.4. The patient was oriented to time, place, and person. Her speech was fluent, with intact naming, repetition, and comprehension. She had impaired abstraction and mildly impaired attention. She was unable to recall three objects after a delay. Intermittently during the examination, she had visual hallucinations that she knew were not real. Cranial nerve examination was unremarkable. Strength was 5/5 throughout, except in the left leg (4/5). Reflexes were brisk throughout, including 3+ reflexes in the arms and the right lower leg; pectoralis reflexes and a jaw jerk were present. No ankle clonus was noted. Examinations for tone, sensation, and cerebellar function were unremarkable. The remainder of the examination was normal. Laboratory test results are shown in Table 1.
Dr. Gonzalez: MRI of the head was performed (Figure 1). FLAIR images showed slight progression of the diffuse subarachnoid hyperintensities and leptomeningeal enhancement. Susceptibility-weighted images showed frontal superficial siderosis and scattered lobar microhemorrhages. Computed tomographic (CT) angiography of the head revealed patent cranial vessels, without evidence of aneurysm, arteriovenous malformation, or thrombosis. A CT scan of the chest and abdomen, obtained after the administration of intravenous contrast material, was normal.	
Figure 1 
Dr. Manzano: Lumbar puncture was performed. On CSF analysis, the nucleated-cell count was 28 per microliter (reference range, 0 to 5), the lymphocyte count 85%, the red-cell count 53 per microliter, and the protein level 280 mg per deciliter. CSF was sent for culture and cytologic studies; other laboratory test results are shown in Table 1. An EEG was normal.
The patient was admitted to this hospital, and intravenous ceftriaxone, acyclovir, and methylprednisolone were administered. During the first 48 hours, the patient was agitated and impulsive. Visual hallucinations worsened, and olanzapine was administered. The CSF culture was negative, and the CSF cytologic studies showed no malignant cells.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old woman was admitted to this hospital with cognitive impairment, headache, and memory loss.
The patient had been well until 6 weeks before admission, when respiratory symptoms developed. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative. At around the same time, coworkers observed a decline in the patient's performance at work. The patient noticed that she was having difficulty operating computers and was forgetting her personal passwords.
The patient was evaluated at another hospital. Although she reported recent confusion and changes in cognitive performance, the examination at that time - including a neurologic examination with assessment of orientation, speech, and memory recall after 5 and 20 minutes - was unremarkable. The patient was referred for an outpatient neurologic evaluation.
One week later (5 weeks before admission), severe headache developed suddenly, along with blurred vision, dizziness, and nausea. After the administration of ondansetron, the blurred vision, dizziness, and nausea resolved; after the administration of nonsteroidal antiinflammatory drugs, the headache became less severe, with mild pain and intermittent episodes of more severe pain.
Three weeks before admission, the patient was seen in a neurology clinic affiliated with the other hospital. She had difficulty recalling the history of her symptoms. On examination, she was oriented to place and person only and was unable to perform serial sevens calculations or to spell ""world"" backward. The remainder of the examination was unremarkable. The complete blood count with differential count and test results for liver and kidney function were normal, as were blood levels of electrolytes, glucose, thiamine, and cobalamin. Tests for syphilis and human immunodeficiency virus infection were negative; other laboratory test results are shown in Table 1. An electroencephalogram (EEG) showed no distinct epileptiform activity. Topiramate was prescribed for a working diagnosis of complex migraine. Imaging studies were obtained.	
Table 1 
Dr. R. Gilberto Gonzalez: Magnetic resonance imaging (MRI) of the head was performed. T2-weighted fluid-attenuated inversion recovery (FLAIR) images showed diffusely scattered hyperintensities in the periventricular, subcortical, and deep white matter and leptomeningeal enhancement. In addition, there was evidence of frontal superficial siderosis and a few scattered microhemorrhages.
Dr. Manzano: Lumbar puncture was also performed. On cerebrospinal fluid (CSF) analysis, the white-cell count was 46 per microliter (reference range, 0 to 5), with a lymphocyte count of 99% (reference range, 40 to 80), the red-cell count was 35 per microliter (reference value, 0), and the protein level was 221 mg per deciliter (reference range, 13 to 40); other laboratory test results are shown in Table 1. Cultures of the CSF were negative. The administration of topiramate was stopped; treatment with oral doxycycline was started but then was stopped after 5 days, when results of a test for Borrelia burgdorferi were interpreted as negative.
Over the next 3 weeks, intermittent headache persisted and cognitive impairment worsened. The patient presented to the emergency department of this hospital. She was unable to provide a history. According to the patient's husband, the patient had stopped working and was no longer able to effectively care for herself, requiring assistance with daily activities such as bathing, dressing, and eating. She had difficulty planning and was unable to put on clothes in the correct sequence or to turn on the shower. Memory impairment persisted, conversation was tangential, and visual hallucinations frequently occurred. The patient had lost 6.8 kg in the past month. There was no fever, rash, or joint pain.
The patient had a history of poliomyelitis in childhood, with residual mild weakness in the left leg; vitamin B12 deficiency, which had been corrected; and hypothyroidism. Medications included atorvastatin, levothyroxine, sertraline, vitamin B12, and cholecalciferol. She had a known allergy to amoxicillin-clavulanate with an unknown reaction. She was a former smoker with a 40 pack-year history, and she had consumed four alcoholic beverages per week before the onset of the current illness. The patient worked in a health care clinic and lived with her husband in a suburban area of New England. She had not traveled outside the United States. She was an avid gardener; she had a dog but no other animal exposures. Her father had received a diagnosis of Alzheimer's disease at 62 years of age.
On examination, the patient was alert and interactive. The temperature was 36.7[degrees]C, the blood pressure 105/51 mm Hg, the heart rate 56 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while she was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.4. The patient was oriented to time, place, and person. Her speech was fluent, with intact naming, repetition, and comprehension. She had impaired abstraction and mildly impaired attention. She was unable to recall three objects after a delay. Intermittently during the examination, she had visual hallucinations that she knew were not real. Cranial nerve examination was unremarkable. Strength was 5/5 throughout, except in the left leg (4/5). Reflexes were brisk throughout, including 3+ reflexes in the arms and the right lower leg; pectoralis reflexes and a jaw jerk were present. No ankle clonus was noted. Examinations for tone, sensation, and cerebellar function were unremarkable. The remainder of the examination was normal. Laboratory test results are shown in Table 1.
Dr. Gonzalez: MRI of the head was performed (Figure 1). FLAIR images showed slight progression of the diffuse subarachnoid hyperintensities and leptomeningeal enhancement. Susceptibility-weighted images showed frontal superficial siderosis and scattered lobar microhemorrhages. Computed tomographic (CT) angiography of the head revealed patent cranial vessels, without evidence of aneurysm, arteriovenous malformation, or thrombosis. A CT scan of the chest and abdomen, obtained after the administration of intravenous contrast material, was normal.	
Figure 1 
Dr. Manzano: Lumbar puncture was performed. On CSF analysis, the nucleated-cell count was 28 per microliter (reference range, 0 to 5), the lymphocyte count 85%, the red-cell count 53 per microliter, and the protein level 280 mg per deciliter. CSF was sent for culture and cytologic studies; other laboratory test results are shown in Table 1. An EEG was normal.
The patient was admitted to this hospital, and intravenous ceftriaxone, acyclovir, and methylprednisolone were administered. During the first 48 hours, the patient was agitated and impulsive. Visual hallucinations worsened, and olanzapine was administered. The CSF culture was negative, and the CSF cytologic studies showed no malignant cells.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of cognitive impairment, headache, and memory loss, along with the MRI findings of diffuse subarachnoid hyperintensities and leptomeningeal enhancement, suggest a neurological condition. The presence of lymphocytosis and elevated protein in the CSF further supports a neurological disorder. The patient's worsening cognitive impairment and visual hallucinations, despite treatment with antibiotics and steroids, suggest a progressive neurological disease. The presence of superficial siderosis and scattered lobar microhemorrhages on MRI is characteristic of cerebral amyloid angiopathy (CAA). CAA is a neurological condition characterized by the accumulation of amyloid beta protein in the walls of cerebral blood vessels, leading to microhemorrhages and cognitive impairment. \n\nDiagnosis: Cerebral Amyloid Angiopathy.""
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        ""content"": ""The patient presents with cognitive impairment, headache, and memory loss. The MRI shows diffusely scattered hyperintensities in the periventricular, subcortical, and deep white matter and leptomeningeal enhancement, as well as frontal superficial siderosis and a few scattered microhemorrhages. The CSF analysis shows an elevated white-cell count and protein level, indicating inflammation or infection in the central nervous system. The patient's symptoms and the MRI and CSF findings are consistent with encephalitis. Given the patient's history of gardening and living in a suburban area of New England, Lyme disease could be a possibility, but the test for Borrelia burgdorferi was negative. The patient's cognitive impairment, hallucinations, and the presence of superficial siderosis on MRI are suggestive of autoimmune encephalitis, specifically anti-NMDA receptor encephalitis. This condition is often associated with tumors, but the patient's CT scan was normal, indicating that if this is the correct diagnosis, it is a non-paraneoplastic case.\n\nDiagnosis: Anti-NMDA receptor encephalitis.""
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        ""content"": ""The patient is a 64-year-old woman presenting with cognitive impairment, headache, and memory loss. The differential diagnosis for this patient includes neurodegenerative diseases such as Alzheimer's disease, infectious diseases such as meningitis or encephalitis, autoimmune diseases such as multiple sclerosis, and neoplastic diseases such as brain tumors. The patient's history of poliomyelitis, vitamin B12 deficiency, and hypothyroidism are unlikely to be related to her current symptoms. The patient's father had Alzheimer's disease, but her symptoms developed suddenly and are progressing rapidly, which is not typical for Alzheimer's disease. The patient's MRI shows diffusely scattered hyperintensities in the periventricular, subcortical, and deep white matter and leptomeningeal enhancement, which could be seen in multiple sclerosis, but the patient does not have other typical symptoms of multiple sclerosis such as optic neuritis or motor symptoms. The patient's CSF analysis shows an elevated white-cell count and protein level, which could be seen in meningitis or encephalitis, but the patient does not have fever or neck stiffness, and her CSF cultures are negative. The patient's symptoms could also be caused by a brain tumor, but her MRI does not show a mass lesion. The patient's symptoms and imaging findings are most consistent with autoimmune encephalitis, which can cause cognitive impairment, headache, memory loss, and MRI findings of scattered hyperintensities and leptomeningeal enhancement. \n\nDiagnosis: Autoimmune Encephalitis.""
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10.1056/NEJMcpc2107344,"Case 21-2021: A 33-Year-Old Pregnant Woman with Fever, Abdominal Pain, and Headache","White-cell count (per μl)   8860
Differential count (per μl)
Neutrophils   6940
Lymphocytes   1320
Monocytes   450
Eosinophils   80
Basophils  00 10
Hemoglobin (g/dl)   7.7
Hematocrit (%)   27.1
Platelet count (per μl)   338,000
Sodium (mmol/liter)   134
Potassium (mmol/liter)   3.3
Chloride (mmol/liter)   98
Carbon dioxide (mmol/liter)   20
Anion gap (mmol/liter)   16
Urea nitrogen (mg/dl)   10
Creatinine (mg/dl)   0.64
Glucose (mg/dl) 7 0 98
Protein (g/dl)
Total 6. .3 7.1
Albumin   3.7
Globulin   3.9
Alanine aminotransferase (U/liter)   25
Aspartate aminotransferase (U/liter)   25
Alkaline phosphatase (U/liter)   30
Lactic acid (mmol/liter)   1.7
C-reactive protein (mg/liter)  .0 6.5
Erythrocyte sedimentation rate (mm/hr)  0 16",Listeria monocytogenes bacteremia resulting in loss of fetus,Listeria infection,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 33-year-old pregnant woman with ulcerative colitis was admitted to this hospital during the summer at 10 weeks of gestation because of fever, nausea, vomiting, abdominal pain and tenderness, and headache.
The patient had been in her usual state of health until 3 days before this admission, when fever, rigors, nausea, and vomiting developed. During the next 3 days, the symptoms worsened; the patient was unable to eat, drink, or take medications. She reported abdominal pain and cramping on the left side that she described as being similar to previous flares of ulcerative colitis; she also had nonbloody diarrhea. The patient called the obstetrics clinic and was instructed to seek evaluation in the emergency department of this hospital.
A review of systems was notable for fatigue, mild headache, neck pain, and photophobia. The patient reported no hematochezia, pelvic pain, vaginal bleeding, dysuria, or joint pain. Ulcerative colitis had been diagnosed 11 years earlier; at the time of the diagnosis, she began treatment with azathioprine but stopped after 1 year because of severe fatigue. The patient had taken mesalamine and sulfasalazine intermittently for disease flares but typically stopped after a few months of treatment. Exacerbations of ulcerative colitis occurred approximately every year and were associated with fevers, rigors, nausea, vomiting, abdominal pain, and bloody diarrhea.
Nine months before this admission, Clostridioides difficile colitis developed, and the patient was successfully treated with oral vancomycin. Three weeks before the current admission, she was admitted to this hospital for a flare of ulcerative colitis; intravenous methylprednisolone, hydromorphone, and ondansetron were administered, and mesalamine was restarted. Flexible sigmoidoscopy revealed mild erythema and friable mucosa with a decreased vascular pattern in the sigmoid colon.
Dr. Craig R. Audin: A transvaginal ultrasound image obtained during that admission showed a single viable intrauterine pregnancy at 7 weeks of gestation and trace subchorionic hemorrhage.
Dr. Tran: The patient was discharged after 7 days once most of the symptoms had abated, although nausea persisted. The patient had had two previous successful pregnancies that had resulted in cesarean deliveries at full term. The patient reported that she had received all the usual childhood immunizations. Routine prenatal serologic screening during the current pregnancy showed immunity to varicella but not to rubella. Tests for syphilis, hepatitis B virus surface antigen, gonorrhea, chlamydia, and human immunodeficiency virus (HIV) were negative. Other history included anemia, chronic back pain, migraines, post-traumatic stress disorder, depression, and anxiety.
At the time of the current admission, medications included prednisone, mesalamine, omeprazole, ondansetron, hydromorphone, tramadol, cyclobenzaprine, sumatriptan, gabapentin, lorazepam, sertraline, pyridoxine, cholecalciferol, and prenatal vitamins. There were no known drug allergies. The patient lived in an urban area of New England with her male partner, with whom she was monogamous, as well as her two children. She worked as an administrator. She did not eat sushi or rare or raw meat, and she did not consume unpasteurized milk or cheese. She had no known sick contacts or exposure to animals. The patient did not smoke tobacco, drink alcohol, or use illicit substances. Her mother had coronary artery disease, her father inflammatory bowel disease, and her sister depression. Her brother and two children were well.
On examination, the temperature was 38.2[degrees]C, the blood pressure 118/61 mm Hg, the pulse 116 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She appeared tired and uncomfortable. The abdominal examination was remarkable for a healed surgical scar; there was diffuse tenderness that was most painful in the lower quadrants. The remainder of the examination was normal. The hemoglobin level was 7.7 g per deciliter (reference range, 12.0 to 16.0), which was similar to the patient's baseline level. Urinalysis was normal. Blood specimens were obtained for microbiologic culture. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Audin: Color Doppler ultrasonography of the abdomen revealed mild fullness in the pelvicalyceal system on the right side (Figure 1A) that is probably a physiologic finding in pregnancy. There was trace fluid in the right lower quadrant; however, the appendix was not visualized (Figure 1B).	
Figure 1 
Dr. Tran: Intravenous fluids, ondansetron, acetaminophen, and hydromorphone were administered; mesalamine was continued, and a tapering of the prednisone dose was begun. The patient was admitted to the hospital for further evaluation and care.
The next day, the abdominal pain persisted and was most severe in the right upper and right lower quadrants. The headache had increased in severity; it was pulsating in quality and was worst in the frontal region, with radiation to the occipital region and posterior neck. There was mild photophobia but no neck stiffness or limitation in the range of motion in the neck. Empirical treatment with intravenous ampicillin-sulbactam and prophylaxis with oral vancomycin were started.
On the third hospital day, the systolic blood pressure declined to 70 mm Hg; after intravenous fluids were administered, the systolic blood pressure increased to 100 mm Hg. Ultrasound images of the uterus obtained at the bedside confirmed a fetal heartbeat. A lumbar puncture was performed. The cerebrospinal fluid (CSF) was clear and colorless, with a glucose level of 63 mg per deciliter (3.5 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]) and a protein level of 17 mg per deciliter (reference range, 5 to 55). There were 0 nucleated cells per microliter (reference range, 0 to 5). Gram's staining of the CSF revealed no neutrophils and very few mononuclear cells; no organisms were identified.
Dr. Audin: Three days later, abdominal magnetic resonance imaging (MRI) (Figure 1C through 1F), performed without the administration of intravenous contrast material, revealed a normal gravid uterus. On T2-weighted imaging, there were rounded areas of myometrial thickening with low signal intensity that were consistent with focal myometrial contractions, as well as a thin band of low signal intensity surrounding the fetus that was consistent with chorioamniotic separation; both of these findings were considered to be normal in the first trimester. The appendix was normal, without wall thickening, dilatation, or adjacent inflammatory changes. Although evaluation of the bowel was limited in the absence of oral and intravenous contrast material, the rectum also appeared normal, without obvious signs of active or chronic inflammation.
A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 33-year-old pregnant woman with ulcerative colitis was admitted to this hospital during the summer at 10 weeks of gestation because of fever, nausea, vomiting, abdominal pain and tenderness, and headache.
The patient had been in her usual state of health until 3 days before this admission, when fever, rigors, nausea, and vomiting developed. During the next 3 days, the symptoms worsened; the patient was unable to eat, drink, or take medications. She reported abdominal pain and cramping on the left side that she described as being similar to previous flares of ulcerative colitis; she also had nonbloody diarrhea. The patient called the obstetrics clinic and was instructed to seek evaluation in the emergency department of this hospital.
A review of systems was notable for fatigue, mild headache, neck pain, and photophobia. The patient reported no hematochezia, pelvic pain, vaginal bleeding, dysuria, or joint pain. Ulcerative colitis had been diagnosed 11 years earlier; at the time of the diagnosis, she began treatment with azathioprine but stopped after 1 year because of severe fatigue. The patient had taken mesalamine and sulfasalazine intermittently for disease flares but typically stopped after a few months of treatment. Exacerbations of ulcerative colitis occurred approximately every year and were associated with fevers, rigors, nausea, vomiting, abdominal pain, and bloody diarrhea.
Nine months before this admission, Clostridioides difficile colitis developed, and the patient was successfully treated with oral vancomycin. Three weeks before the current admission, she was admitted to this hospital for a flare of ulcerative colitis; intravenous methylprednisolone, hydromorphone, and ondansetron were administered, and mesalamine was restarted. Flexible sigmoidoscopy revealed mild erythema and friable mucosa with a decreased vascular pattern in the sigmoid colon.
Dr. Craig R. Audin: A transvaginal ultrasound image obtained during that admission showed a single viable intrauterine pregnancy at 7 weeks of gestation and trace subchorionic hemorrhage.
Dr. Tran: The patient was discharged after 7 days once most of the symptoms had abated, although nausea persisted. The patient had had two previous successful pregnancies that had resulted in cesarean deliveries at full term. The patient reported that she had received all the usual childhood immunizations. Routine prenatal serologic screening during the current pregnancy showed immunity to varicella but not to rubella. Tests for syphilis, hepatitis B virus surface antigen, gonorrhea, chlamydia, and human immunodeficiency virus (HIV) were negative. Other history included anemia, chronic back pain, migraines, post-traumatic stress disorder, depression, and anxiety.
At the time of the current admission, medications included prednisone, mesalamine, omeprazole, ondansetron, hydromorphone, tramadol, cyclobenzaprine, sumatriptan, gabapentin, lorazepam, sertraline, pyridoxine, cholecalciferol, and prenatal vitamins. There were no known drug allergies. The patient lived in an urban area of New England with her male partner, with whom she was monogamous, as well as her two children. She worked as an administrator. She did not eat sushi or rare or raw meat, and she did not consume unpasteurized milk or cheese. She had no known sick contacts or exposure to animals. The patient did not smoke tobacco, drink alcohol, or use illicit substances. Her mother had coronary artery disease, her father inflammatory bowel disease, and her sister depression. Her brother and two children were well.
On examination, the temperature was 38.2[degrees]C, the blood pressure 118/61 mm Hg, the pulse 116 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She appeared tired and uncomfortable. The abdominal examination was remarkable for a healed surgical scar; there was diffuse tenderness that was most painful in the lower quadrants. The remainder of the examination was normal. The hemoglobin level was 7.7 g per deciliter (reference range, 12.0 to 16.0), which was similar to the patient's baseline level. Urinalysis was normal. Blood specimens were obtained for microbiologic culture. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Audin: Color Doppler ultrasonography of the abdomen revealed mild fullness in the pelvicalyceal system on the right side (Figure 1A) that is probably a physiologic finding in pregnancy. There was trace fluid in the right lower quadrant; however, the appendix was not visualized (Figure 1B).	
Figure 1 
Dr. Tran: Intravenous fluids, ondansetron, acetaminophen, and hydromorphone were administered; mesalamine was continued, and a tapering of the prednisone dose was begun. The patient was admitted to the hospital for further evaluation and care.
The next day, the abdominal pain persisted and was most severe in the right upper and right lower quadrants. The headache had increased in severity; it was pulsating in quality and was worst in the frontal region, with radiation to the occipital region and posterior neck. There was mild photophobia but no neck stiffness or limitation in the range of motion in the neck. Empirical treatment with intravenous ampicillin-sulbactam and prophylaxis with oral vancomycin were started.
On the third hospital day, the systolic blood pressure declined to 70 mm Hg; after intravenous fluids were administered, the systolic blood pressure increased to 100 mm Hg. Ultrasound images of the uterus obtained at the bedside confirmed a fetal heartbeat. A lumbar puncture was performed. The cerebrospinal fluid (CSF) was clear and colorless, with a glucose level of 63 mg per deciliter (3.5 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]) and a protein level of 17 mg per deciliter (reference range, 5 to 55). There were 0 nucleated cells per microliter (reference range, 0 to 5). Gram's staining of the CSF revealed no neutrophils and very few mononuclear cells; no organisms were identified.
Dr. Audin: Three days later, abdominal magnetic resonance imaging (MRI) (Figure 1C through 1F), performed without the administration of intravenous contrast material, revealed a normal gravid uterus. On T2-weighted imaging, there were rounded areas of myometrial thickening with low signal intensity that were consistent with focal myometrial contractions, as well as a thin band of low signal intensity surrounding the fetus that was consistent with chorioamniotic separation; both of these findings were considered to be normal in the first trimester. The appendix was normal, without wall thickening, dilatation, or adjacent inflammatory changes. Although evaluation of the bowel was limited in the absence of oral and intravenous contrast material, the rectum also appeared normal, without obvious signs of active or chronic inflammation.
A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Listeria monocytogenes bacteremia and meningitis. The patient's symptoms of fever, nausea, vomiting, abdominal pain, and headache, along with her history of ulcerative colitis and pregnancy, suggest an infectious process. The patient's immunocompromised state due to her ulcerative colitis and pregnancy makes her more susceptible to infections such as Listeria monocytogenes, which can cause bacteremia and meningitis. The patient's symptoms did not improve with initial treatment, suggesting a more resistant or unusual pathogen. The cerebrospinal fluid (CSF) findings of low nucleated cells and no organisms identified on Gram's stain are consistent with Listeria meningitis, which can often present with a paucity of cells and negative Gram's stain. The patient's consumption of unpasteurized milk or cheese could have been a source of Listeria infection.""
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        ""content"": ""The patient's symptoms of fever, nausea, vomiting, abdominal pain and tenderness, and headache, along with her history of ulcerative colitis and recent flare, initially suggest a possible exacerbation of her ulcerative colitis or an infection. However, her symptoms did not improve with treatment for ulcerative colitis and her lab results did not indicate an infection. The patient's headache and photophobia could suggest meningitis, but a lumbar puncture showed no signs of infection in the cerebrospinal fluid. The patient's low blood pressure could suggest sepsis, but again, her lab results did not indicate an infection. The patient's symptoms, along with her history of ulcerative colitis, could suggest a possible autoimmune condition. However, the patient's symptoms did not improve with treatment for ulcerative colitis and her lab results did not indicate an autoimmune condition. Given the patient's symptoms and the results of her lab tests and imaging studies, the most likely diagnosis is Listeria monocytogenes infection. This infection can cause symptoms similar to those the patient is experiencing, and it can be contracted through contaminated food, which fits with the patient's history of eating sushi and raw meat. Additionally, Listeria monocytogenes infection can be more severe in pregnant women, which could explain the severity of the patient's symptoms.\n\nDiagnosis: Listeria monocytogenes infection.""
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}",Listeria monocytogenes infection,Y,"{
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        ""content"": ""The patient is a 33-year-old pregnant woman with a history of ulcerative colitis presenting with fever, nausea, vomiting, abdominal pain, and headache. The differential diagnosis for this patient includes a flare of ulcerative colitis, appendicitis, urinary tract infection, preeclampsia, and infectious causes such as listeriosis or toxoplasmosis. The patient's symptoms of fever, nausea, vomiting, and abdominal pain could be consistent with a flare of her ulcerative colitis. However, her abdominal pain is located on the left side, which is not typical for appendicitis, which usually presents with right lower quadrant pain. The patient's urinalysis is normal, making a urinary tract infection unlikely. The patient does not have hypertension or proteinuria, making preeclampsia unlikely. The patient's headache and photophobia could be consistent with meningitis, but her cerebrospinal fluid analysis is normal, making this diagnosis unlikely. The patient's symptoms could also be consistent with an infectious cause such as listeriosis or toxoplasmosis, which can present with fever, headache, and gastrointestinal symptoms. However, the patient does not have a history of consuming raw or undercooked meat, unpasteurized dairy products, or contact with cat feces, which are common sources of these infections. The patient's blood cultures are negative, making a bacterial infection less likely. The patient's abdominal MRI does not show any signs of inflammation or infection in the appendix or rectum. Given the patient's history of ulcerative colitis and her presentation with fever, nausea, vomiting, and abdominal pain, a flare of her ulcerative colitis is the most likely diagnosis.\n\nDiagnosis: Flare of ulcerative colitis.""
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10.1056/NEJMcpc2004992,Case 20-2021: A 69-Year-Old Man with Ataxia,,"Cerebellar ataxia, neuropathy, and vestibular are flexia syndrome due to a biallelic expansion in RFC1","Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 69-year-old man was evaluated in the neurology clinic of this hospital because of progressively worsening ataxia.
The patient had been well until 9 years before this evaluation, when abnormal gait and impaired coordination developed. He was unable to walk in a straight line; he bumped into walls when walking down a hallway. He also had difficulty reading traffic signs while driving and noted a change in the quality of his voice. The patient was evaluated at the neurology clinic of another hospital and began physical therapy.
During the next several years, symptoms gradually worsened despite physical therapy. The patient was no longer able to drive or play golf, and he intermittently used a walker because of unsteadiness. He had frequent falls, including one that led to fractures in six ribs. His speech changes worsened, such that he could no longer sing. The patient was referred to the neurology clinic of this hospital for evaluation.
In the neurology clinic, the patient reported frequent bowel movements, approximately 10 per day. He had no vertigo, lightheadedness, hearing loss, tremor, erectile dysfunction, disturbance of sleep, or urinary incontinence. He reported a sense of visual disorientation with head movement and with changes in the direction of gaze. He had a history of hyperlipidemia. Medications included atorvastatin, cetirizine, and a multivitamin; there were no known drug allergies. The patient had recently moved from an urban area in the southeastern United States to a suburban area of New England. He drank one glass of wine nightly; additional alcohol use caused worsening of ataxia and dysarthria. He had previously smoked five cigarettes daily but had quit smoking 30 years before this evaluation; he did not use illicit drugs.
The patient's mother had died of heart failure at an elderly age, and his father had died after a stroke and myocardial infarction at 70 years of age. The patient had two adult children, who were healthy. His two brothers and one of his sisters had celiac disease; the sister also reportedly had a shuffling gait. The sister's daughter had received a diagnosis of Turner's syndrome and had been seen by a neurologist for a balance disturbance. A brother's grandson also had celiac disease and a gait disturbance (Figure 1).	
Figure 1 
The temperature was 36.6[degrees]C, the blood pressure 136/88 mm Hg, and the pulse 72 beats per minute. The patient was alert, oriented, and attentive and provided a detailed history. He had moderate dysarthria, with impairment in the rate, rhythm, and clarity of speech. An oculomotor examination revealed complete and conjugate gaze in all directions; he had intact smooth pursuit movements but had slow, dysmetric saccades. Results of a head impulse test were abnormal, with corrective saccades noted bilaterally. Normal tone and full strength were present in all major muscle groups of the arms and legs. Reflexes were 2+ and symmetric at the knees but absent at the ankles. Plantar responses were flexor bilaterally. Rapid tapping of the index fingers on the thumbs was dysrhythmic and uncoordinated. Finger-nose-finger testing revealed mild intention tremor. Heel-to-shin testing revealed symmetric jerking movements with lateral movements across the shins. Vibration and joint-position senses in the legs were profoundly decreased: the patient was unable to sense vibration at the toes, had a decreased ability to sense vibration at the knees, and had difficulty discerning the position of his big toe with his eyes closed. There was sway in his stance, regardless of whether his eyes were open, and he could not stand with the feet together. The patient walked without support. He had a wide-based gait with considerable staggering and jerky, stiff movements of the legs. He was unable to maintain balance in a tandem stance or to walk with a tandem gait.
The complete blood count and blood levels of electrolytes were normal, as were test results for kidney, liver, and thyroid function; antibodies to thyroid peroxidase and thyroglobulin were not detected. Blood levels of cyanocobalamin, methylmalonic acid, vitamin E, and glycated hemoglobin were normal; anti-glutamic acid decarboxylase antibodies and tissue transglutaminase antibodies were not detected. Results of serum protein electrophoresis were normal. Genetic testing revealed no mutations in genes associated with spinocerebellar ataxia types 1, 2, 3, 6, and 8. Clinical testing of otolith function revealed abnormal vestibular-evoked myogenic potentials on the left side. Nerve-conduction studies revealed absent or barely detectable responses in the bilateral sural nerves, left superficial peroneal nerve, left median nerve, left ulnar nerve, and right radial nerve. Results of motor nerve-conduction studies were normal, as were results of a modified barium-swallow evaluation. A previous workup at another hospital for chronic diarrhea had reportedly been normal, with no evidence of malabsorption.
Dr. McKinley Glover: Magnetic resonance imaging (MRI) of the head (Figure 2), performed without the administration of intravenous contrast material, revealed mild diffuse parenchymal volume loss and prominent cerebellar volume loss, most notably involving the vermis and superior cerebellar hemispheres. There was mild flattening of the superior margin of the midbrain, and the ratio of midbrain to ventral pons was mildly reduced at 0.51 (reference range, >0.52).1 The anteroposterior diameter of the midbrain was 8.90 mm (reference range, >9.35).1 There was no abnormal signal in the pons, and the middle cerebellar peduncles were normal. There was a chronic lacunar infarct of the right thalamus.	
Figure 2 
Dr. de Gusmao: Additional history was obtained, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 69-year-old man was evaluated in the neurology clinic of this hospital because of progressively worsening ataxia.
The patient had been well until 9 years before this evaluation, when abnormal gait and impaired coordination developed. He was unable to walk in a straight line; he bumped into walls when walking down a hallway. He also had difficulty reading traffic signs while driving and noted a change in the quality of his voice. The patient was evaluated at the neurology clinic of another hospital and began physical therapy.
During the next several years, symptoms gradually worsened despite physical therapy. The patient was no longer able to drive or play golf, and he intermittently used a walker because of unsteadiness. He had frequent falls, including one that led to fractures in six ribs. His speech changes worsened, such that he could no longer sing. The patient was referred to the neurology clinic of this hospital for evaluation.
In the neurology clinic, the patient reported frequent bowel movements, approximately 10 per day. He had no vertigo, lightheadedness, hearing loss, tremor, erectile dysfunction, disturbance of sleep, or urinary incontinence. He reported a sense of visual disorientation with head movement and with changes in the direction of gaze. He had a history of hyperlipidemia. Medications included atorvastatin, cetirizine, and a multivitamin; there were no known drug allergies. The patient had recently moved from an urban area in the southeastern United States to a suburban area of New England. He drank one glass of wine nightly; additional alcohol use caused worsening of ataxia and dysarthria. He had previously smoked five cigarettes daily but had quit smoking 30 years before this evaluation; he did not use illicit drugs.
The patient's mother had died of heart failure at an elderly age, and his father had died after a stroke and myocardial infarction at 70 years of age. The patient had two adult children, who were healthy. His two brothers and one of his sisters had celiac disease; the sister also reportedly had a shuffling gait. The sister's daughter had received a diagnosis of Turner's syndrome and had been seen by a neurologist for a balance disturbance. A brother's grandson also had celiac disease and a gait disturbance (Figure 1).	
Figure 1 
The temperature was 36.6[degrees]C, the blood pressure 136/88 mm Hg, and the pulse 72 beats per minute. The patient was alert, oriented, and attentive and provided a detailed history. He had moderate dysarthria, with impairment in the rate, rhythm, and clarity of speech. An oculomotor examination revealed complete and conjugate gaze in all directions; he had intact smooth pursuit movements but had slow, dysmetric saccades. Results of a head impulse test were abnormal, with corrective saccades noted bilaterally. Normal tone and full strength were present in all major muscle groups of the arms and legs. Reflexes were 2+ and symmetric at the knees but absent at the ankles. Plantar responses were flexor bilaterally. Rapid tapping of the index fingers on the thumbs was dysrhythmic and uncoordinated. Finger-nose-finger testing revealed mild intention tremor. Heel-to-shin testing revealed symmetric jerking movements with lateral movements across the shins. Vibration and joint-position senses in the legs were profoundly decreased: the patient was unable to sense vibration at the toes, had a decreased ability to sense vibration at the knees, and had difficulty discerning the position of his big toe with his eyes closed. There was sway in his stance, regardless of whether his eyes were open, and he could not stand with the feet together. The patient walked without support. He had a wide-based gait with considerable staggering and jerky, stiff movements of the legs. He was unable to maintain balance in a tandem stance or to walk with a tandem gait.
The complete blood count and blood levels of electrolytes were normal, as were test results for kidney, liver, and thyroid function; antibodies to thyroid peroxidase and thyroglobulin were not detected. Blood levels of cyanocobalamin, methylmalonic acid, vitamin E, and glycated hemoglobin were normal; anti-glutamic acid decarboxylase antibodies and tissue transglutaminase antibodies were not detected. Results of serum protein electrophoresis were normal. Genetic testing revealed no mutations in genes associated with spinocerebellar ataxia types 1, 2, 3, 6, and 8. Clinical testing of otolith function revealed abnormal vestibular-evoked myogenic potentials on the left side. Nerve-conduction studies revealed absent or barely detectable responses in the bilateral sural nerves, left superficial peroneal nerve, left median nerve, left ulnar nerve, and right radial nerve. Results of motor nerve-conduction studies were normal, as were results of a modified barium-swallow evaluation. A previous workup at another hospital for chronic diarrhea had reportedly been normal, with no evidence of malabsorption.
Dr. McKinley Glover: Magnetic resonance imaging (MRI) of the head (Figure 2), performed without the administration of intravenous contrast material, revealed mild diffuse parenchymal volume loss and prominent cerebellar volume loss, most notably involving the vermis and superior cerebellar hemispheres. There was mild flattening of the superior margin of the midbrain, and the ratio of midbrain to ventral pons was mildly reduced at 0.51 (reference range, >0.52).1 The anteroposterior diameter of the midbrain was 8.90 mm (reference range, >9.35).1 There was no abnormal signal in the pons, and the middle cerebellar peduncles were normal. There was a chronic lacunar infarct of the right thalamus.	
Figure 2 
Dr. de Gusmao: Additional history was obtained, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Multiple System Atrophy (MSA)\n\nThe patient's symptoms of progressive ataxia, dysarthria, and visual disorientation with head movement and changes in gaze direction suggest a neurodegenerative disorder. The absence of vertigo, lightheadedness, hearing loss, tremor, erectile dysfunction, sleep disturbance, or urinary incontinence helps to narrow down the possibilities. The patient's family history of celiac disease and gait disturbances suggests a possible genetic component. The physical examination findings of dysarthria, dysmetric saccades, absent ankle reflexes, dysrhythmic and uncoordinated finger tapping, intention tremor, jerky movements during heel-to-shin testing, and decreased vibration and joint-position senses in the legs further support a neurodegenerative disorder. The MRI findings of diffuse parenchymal volume loss and prominent cerebellar volume loss, particularly in the vermis and superior cerebellar hemispheres, along with mild flattening of the superior margin of the midbrain, are consistent with Multiple System Atrophy (MSA), a rare neurodegenerative disorder characterized by autonomic dysfunction, parkinsonism, and ataxia. The absence of mutations in genes associated with spinocerebellar ataxia types 1, 2, 3, 6, and 8 further supports the diagnosis of MSA.""
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        ""content"": ""The patient's symptoms of progressively worsening ataxia, abnormal gait, impaired coordination, difficulty reading traffic signs, and change in voice quality are indicative of a neurodegenerative disorder. The patient's family history of celiac disease and gait disturbances further supports a genetic cause. The MRI findings of prominent cerebellar volume loss, particularly in the vermis and superior cerebellar hemispheres, and mild flattening of the superior margin of the midbrain are consistent with a diagnosis of spinocerebellar ataxia. However, genetic testing did not reveal mutations in genes associated with common types of spinocerebellar ataxia (types 1, 2, 3, 6, and 8). The patient's profound decrease in vibration and joint-position senses in the legs, abnormal vestibular-evoked myogenic potentials, and abnormal nerve-conduction studies suggest a sensory neuropathy. Taken together, these findings are consistent with a diagnosis of spinocerebellar ataxia with neuropathy, specifically, spinocerebellar ataxia type 11, which is a rare form of the disease not included in the initial genetic testing.\n\nDiagnosis: Spinocerebellar ataxia type 11.""
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        ""content"": ""The patient is a 69-year-old man presenting with progressively worsening ataxia, dysarthria, and frequent bowel movements. The differential diagnosis for this patient includes cerebellar ataxia, multiple system atrophy, spinocerebellar ataxia, and Friedreich's ataxia. The patient's MRI shows prominent cerebellar volume loss, particularly in the vermis and superior cerebellar hemispheres, which is consistent with cerebellar ataxia. However, the patient's age and the absence of a family history of ataxia make this diagnosis less likely. Multiple system atrophy could also explain the patient's symptoms, but this condition typically presents with autonomic dysfunction, which the patient does not have. Spinocerebellar ataxia is a genetic disorder that causes degeneration of the cerebellum, but genetic testing did not reveal any mutations associated with this condition. Friedreich's ataxia is another genetic disorder that causes progressive damage to the nervous system, but this condition typically presents in childhood. The patient's family history of celiac disease and gait disturbances, along with his own frequent bowel movements, suggest that he may have gluten ataxia, a form of ataxia caused by an immune response to gluten. This diagnosis is further supported by the fact that the patient's symptoms have been gradually worsening over several years, which is consistent with the progressive nature of gluten ataxia.\n\nDiagnosis: Gluten ataxia.""
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10.1056/NEJMcpc2100272,"Case 19-2021: A 54-Year-Old Man with Irritability, Confusion, and Odd Behaviors",,Delayed posthypoxic leukoencephalopathy,Delayed posthypoxic leukoencephalopathy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 54-year-old man was evaluated by the neuropsychology service of this hospital because of irritability, confusion, and odd behaviors.
The patient had been in his usual state of health until 9 months before the current evaluation, when he received a diagnosis of squamous-cell carcinoma of the tongue that had metastasized to the cervical lymph nodes. He underwent surgical dissection of the neck and resection of the tongue base on the right side, followed by adjuvant radiation therapy, which resulted in cancer remission. After treatment, neck pain and shoulder weakness developed and was attributed to postoperative neuropathy involving the right spinal accessory nerve.
In the context of this illness and persistent pain, the patient sought care at the cancer center behavioral medicine clinic of this hospital and received a diagnosis of adjustment disorder with depression and anxiety. During the next 8 months, the patient was seen for psychotherapy approximately every 2 weeks. Treatment for the pain included physical therapy, occupational therapy, massage therapy, acupuncture, trigger-point injections, and the use of a scapular elevation brace. Therapy with oxycodone, methadone, gabapentin, tizanidine, and duloxetine was started. Four months before the current evaluation, a sural nerve graft was placed in the right spinal accessory nerve from the proximal, functioning portion to the distal portion, but the pain and weakness did not abate.
Six weeks before the current evaluation, the patient did not respond to telephone calls for 24 hours. The police were called and found the patient unresponsive with prescription medication bottles nearby. Emergency medical services personnel arrived, and the initial evaluation, in the patient's home, was notable for a severely decreased respiratory rate. Naloxone was administered, the trachea was intubated, and the patient was taken to a local hospital. In the emergency department, the patient was pulseless with ongoing electrocardiographic activity. Cardiopulmonary resuscitation was performed, and epinephrine was administered; after 4 minutes, spontaneous circulation was restored. The dose of methadone was decreased, and therapy with oxycodone, gabapentin, and tizanidine was stopped. During the subsequent 6 days, septic shock, aspiration pneumonia, acute kidney injury, and delirium occurred. When these problems resolved, the patient was discharged home.
Five weeks before the current evaluation, the patient participated in a video follow-up evaluation at the behavioral medicine clinic. He expressed embarrassment and frustration related to his apparent accidental overdose. He described persistent depression, increased anxiety, and no other new symptoms.
Two weeks before the current evaluation, the patient missed a routine video follow-up evaluation at the behavioral medicine clinic, and his family was called. For the preceding 2 weeks, they had noticed that the patient was uncharacteristically agitated, irritable, talking loudly, and verbally abusive. Odd behaviors were reported. The patient had gotten lost while driving to a friend's house that he visited frequently, had been pulled over by police for driving erratically (with normal results on a breathalyzer test), and on another occasion, had been found walking along the highway under an overpass. He called family members repeatedly in the middle of the night, and he would not answer when the calls were returned. When the family requested a police wellness check of the patient, the patient retaliated by requesting a police wellness check of the family members. After this incident, the family was advised to take the patient to a local hospital for admission.
At the local hospital, the patient reported no symptoms and noted that he had stopped taking methadone because he was concerned about a medication overdose. The Montreal Cognitive Assessment score was 19, indicating cognitive impairment; scores range from 0 to 30, with higher scores indicating better cognitive function.1 Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed a nonspecific hypodensity in the centrum semiovale on the left side. The patient was told he had mild dementia. Visiting nurse services were arranged, and the patient was discharged home.
One week before the current evaluation, the patient's family reported that he had increased confusion and odd behaviors. He was unable to recall details of conversations that had happened minutes before. He could not operate the telephone or remote control and had emptied the trash can into the toilet. He had asked for his clothes to be cut off because he felt uncomfortable. Family members had been staying with the patient every night since his recent discharge because they were concerned about his safety. A neuropsychological evaluation was requested.
Dr. Michael W. Parsons: The evaluation was conducted by the cancer center neuropsychology service of this hospital with the use of videoconferencing technology to reduce the risk of exposure to coronavirus disease 2019 (Covid-19). The patient acknowledged only minimal cognitive changes and was dismissive of the family's concerns. A review of systems was notable for fatigue, moderate depression, mild anxiety, and difficulty sleeping and keeping track of time.
Additional history obtained from the patient's family included insomnia, lumbar disk herniation, olecranon bursitis, and an inguinal hernia that had led to surgical repair in early adulthood. He had had multiple concussions as a teenager, as well as a brief loss of consciousness during a motor vehicle collision 3 years earlier. After the collision, fatigue, headaches, difficulty concentrating, and impaired memory occurred; during the subsequent 2 years, occupational therapy was provided, and the symptoms gradually resolved.
Medications at the time of evaluation included ibuprofen, acetaminophen, duloxetine, trazodone, melatonin, polyethylene glycol, and multivitamins. There were no known drug allergies. The patient lived alone in a suburban area of New England with family members nearby. He had completed a master's degree and had had a successful career; he had taken a leave of absence from work 9 months earlier in anticipation of cancer treatment. After cancer treatment, he had been unable to return to work because of pain. He was athletic, walked 3 miles daily, and enjoyed golfing. He rarely drank alcohol and had never smoked tobacco or used illicit drugs. His family history included breast cancer and dementia in his mother, hearing loss and hypertension in his father, metastatic cancer with an unknown primary source in his paternal grandfather, glaucoma and alcohol use disorder in his maternal grandmother, and a brain tumor in a more distant relative.
On video neuropsychological examination, the patient was in no distress and was adequately groomed, with normal-appearing hygiene. His affect was irritable, and the fact that he reported no symptoms suggested limited insight. His spontaneous speech was fluent and well articulated. His thoughts were tangential, and he was frequently forgetful and easily distracted; his information processing speed was slow. A formal neuropsychological assessment revealed impaired executive functioning, marked by disinhibition and poor working memory, as well as deficits in recent memory, verbal fluency, and information processing speed.
Dr. Bullis: A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 54-year-old man was evaluated by the neuropsychology service of this hospital because of irritability, confusion, and odd behaviors.
The patient had been in his usual state of health until 9 months before the current evaluation, when he received a diagnosis of squamous-cell carcinoma of the tongue that had metastasized to the cervical lymph nodes. He underwent surgical dissection of the neck and resection of the tongue base on the right side, followed by adjuvant radiation therapy, which resulted in cancer remission. After treatment, neck pain and shoulder weakness developed and was attributed to postoperative neuropathy involving the right spinal accessory nerve.
In the context of this illness and persistent pain, the patient sought care at the cancer center behavioral medicine clinic of this hospital and received a diagnosis of adjustment disorder with depression and anxiety. During the next 8 months, the patient was seen for psychotherapy approximately every 2 weeks. Treatment for the pain included physical therapy, occupational therapy, massage therapy, acupuncture, trigger-point injections, and the use of a scapular elevation brace. Therapy with oxycodone, methadone, gabapentin, tizanidine, and duloxetine was started. Four months before the current evaluation, a sural nerve graft was placed in the right spinal accessory nerve from the proximal, functioning portion to the distal portion, but the pain and weakness did not abate.
Six weeks before the current evaluation, the patient did not respond to telephone calls for 24 hours. The police were called and found the patient unresponsive with prescription medication bottles nearby. Emergency medical services personnel arrived, and the initial evaluation, in the patient's home, was notable for a severely decreased respiratory rate. Naloxone was administered, the trachea was intubated, and the patient was taken to a local hospital. In the emergency department, the patient was pulseless with ongoing electrocardiographic activity. Cardiopulmonary resuscitation was performed, and epinephrine was administered; after 4 minutes, spontaneous circulation was restored. The dose of methadone was decreased, and therapy with oxycodone, gabapentin, and tizanidine was stopped. During the subsequent 6 days, septic shock, aspiration pneumonia, acute kidney injury, and delirium occurred. When these problems resolved, the patient was discharged home.
Five weeks before the current evaluation, the patient participated in a video follow-up evaluation at the behavioral medicine clinic. He expressed embarrassment and frustration related to his apparent accidental overdose. He described persistent depression, increased anxiety, and no other new symptoms.
Two weeks before the current evaluation, the patient missed a routine video follow-up evaluation at the behavioral medicine clinic, and his family was called. For the preceding 2 weeks, they had noticed that the patient was uncharacteristically agitated, irritable, talking loudly, and verbally abusive. Odd behaviors were reported. The patient had gotten lost while driving to a friend's house that he visited frequently, had been pulled over by police for driving erratically (with normal results on a breathalyzer test), and on another occasion, had been found walking along the highway under an overpass. He called family members repeatedly in the middle of the night, and he would not answer when the calls were returned. When the family requested a police wellness check of the patient, the patient retaliated by requesting a police wellness check of the family members. After this incident, the family was advised to take the patient to a local hospital for admission.
At the local hospital, the patient reported no symptoms and noted that he had stopped taking methadone because he was concerned about a medication overdose. The Montreal Cognitive Assessment score was 19, indicating cognitive impairment; scores range from 0 to 30, with higher scores indicating better cognitive function.1 Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed a nonspecific hypodensity in the centrum semiovale on the left side. The patient was told he had mild dementia. Visiting nurse services were arranged, and the patient was discharged home.
One week before the current evaluation, the patient's family reported that he had increased confusion and odd behaviors. He was unable to recall details of conversations that had happened minutes before. He could not operate the telephone or remote control and had emptied the trash can into the toilet. He had asked for his clothes to be cut off because he felt uncomfortable. Family members had been staying with the patient every night since his recent discharge because they were concerned about his safety. A neuropsychological evaluation was requested.
Dr. Michael W. Parsons: The evaluation was conducted by the cancer center neuropsychology service of this hospital with the use of videoconferencing technology to reduce the risk of exposure to coronavirus disease 2019 (Covid-19). The patient acknowledged only minimal cognitive changes and was dismissive of the family's concerns. A review of systems was notable for fatigue, moderate depression, mild anxiety, and difficulty sleeping and keeping track of time.
Additional history obtained from the patient's family included insomnia, lumbar disk herniation, olecranon bursitis, and an inguinal hernia that had led to surgical repair in early adulthood. He had had multiple concussions as a teenager, as well as a brief loss of consciousness during a motor vehicle collision 3 years earlier. After the collision, fatigue, headaches, difficulty concentrating, and impaired memory occurred; during the subsequent 2 years, occupational therapy was provided, and the symptoms gradually resolved.
Medications at the time of evaluation included ibuprofen, acetaminophen, duloxetine, trazodone, melatonin, polyethylene glycol, and multivitamins. There were no known drug allergies. The patient lived alone in a suburban area of New England with family members nearby. He had completed a master's degree and had had a successful career; he had taken a leave of absence from work 9 months earlier in anticipation of cancer treatment. After cancer treatment, he had been unable to return to work because of pain. He was athletic, walked 3 miles daily, and enjoyed golfing. He rarely drank alcohol and had never smoked tobacco or used illicit drugs. His family history included breast cancer and dementia in his mother, hearing loss and hypertension in his father, metastatic cancer with an unknown primary source in his paternal grandfather, glaucoma and alcohol use disorder in his maternal grandmother, and a brain tumor in a more distant relative.
On video neuropsychological examination, the patient was in no distress and was adequately groomed, with normal-appearing hygiene. His affect was irritable, and the fact that he reported no symptoms suggested limited insight. His spontaneous speech was fluent and well articulated. His thoughts were tangential, and he was frequently forgetful and easily distracted; his information processing speed was slow. A formal neuropsychological assessment revealed impaired executive functioning, marked by disinhibition and poor working memory, as well as deficits in recent memory, verbal fluency, and information processing speed.
Dr. Bullis: A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of irritability, confusion, odd behaviors, and cognitive impairment, along with the history of squamous-cell carcinoma of the tongue and subsequent radiation therapy, suggest a possible paraneoplastic syndrome affecting the central nervous system. Paraneoplastic syndromes are rare disorders triggered by an altered immune system response to a neoplasm, and they are defined by clinical manifestations in sites remote from the tumor itself or its metastases. In this case, the patient's cognitive and behavioral changes could be due to a paraneoplastic limbic encephalitis, which is characterized by personality changes, irritability, depression, seizures, memory loss and sometimes dementia. This condition is often associated with small cell lung cancer, but can occur with other cancers. The patient's history of cancer and the onset of symptoms following cancer treatment support this diagnosis.\n\nDiagnosis: Paraneoplastic Limbic Encephalitis.""
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        ""content"": ""The patient is a 54-year-old man with a history of squamous-cell carcinoma of the tongue, who presents with irritability, confusion, and odd behaviors. The differential diagnosis for this patient includes dementia, delirium, depression, medication side effects, and metastasis of the cancer to the brain. The patient's cognitive impairment, as indicated by a Montreal Cognitive Assessment score of 19, suggests dementia. However, the relatively rapid onset of symptoms and fluctuating course are more consistent with delirium. The patient's history of depression and anxiety, as well as his recent accidental overdose, suggest that his mental status changes could be related to a psychiatric condition. However, his lack of response to psychotherapy and the severity of his symptoms make this less likely. The patient's recent changes in medication could potentially be causing his symptoms, but the continuation of symptoms after stopping the medications makes this less likely. Finally, the patient's history of cancer raises the possibility of metastasis to the brain. The patient's CT scan showed a nonspecific hypodensity in the centrum semiovale on the left side, which could potentially be a metastatic lesion. Given the patient's history of cancer and the findings on the CT scan, metastasis to the brain is the most likely diagnosis.\n\nDiagnosis: Metastasis of squamous-cell carcinoma to the brain.""
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10.1056/NEJMcpc2100283,"Case 18-2021: An 81-Year-Old Man with Cough, Fever, and Shortness of Breath","Sodium (mmol/liter)   138
Potassium (mmol/liter)   3.8
Chloride (mmol/liter)   99
Carbon dioxide (mmol/liter) 23. 1.9 18
Urea nitrogen (mg/dl)   17
Creatinine (mg/dl)   1.0
Glucose (mg/dl)   118
Lactic acid (mmol/liter)   3.5
Alanine aminotransferase (U/liter)   70
Aspartate aminotransferase (U/liter)   128
Alkaline phosphatase (U/liter)   128
Total bilirubin (mg/dl)  1.7
Direct bilirubin (mg/dl) 0.  0.5
Albumin (g/dl)   3.5
Hematocrit (%)   44.5
Hemoglobin (g/dl)   15
White-cell count (per μl)   11,920
Differential count (per μl)
Neutrophils   10,100
Lymphocytes   850
Monocytes   600
Eosinophils   40
Immature granulocytes 0–100 280
Platelet count (per μl)   179,000
Prothrombin time (sec)   14.7
Prothrombin-time international 
normalized ratio
  1.2
d-dimer (ng/ml)   >10,000
Fibrinogen (mg/dl) 15 0 679
Ferritin (μg/liter) 2 00 1760
Lactate dehydrogenase (U/liter) 11 10 1340
C-reactive protein (mg/liter)   185
Erythrocyte sedimentation rate (mm/hr)   84
Creatine kinase (U/liter)   1607
N-terminal pro–B-type natriuretic peptide 
(pg/ml)
0–1800 495
High-sensitivity troponin T (ng/liter)   62",Pneumonia associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute pulmonary embolism.,Pneumonia associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute pulmonary embolism.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 81-year-old man was admitted to this hospital with fever, cough, and shortness of breath during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient had been in his usual state of health until 3 days before this admission, when fever and cough developed. On the morning of admission, he noted an abrupt onset of shortness of breath at rest and dyspnea on exertion. There was also substernal chest pain on the left side that worsened with deep breaths and when he lay down. The patient's son called emergency medical services, and the patient was brought to the emergency department of this hospital for further evaluation.
On arrival at the emergency department, the patient described ongoing chest pain and shortness of breath. The son reported that the patient had fallen at home 2 days before admission, but the patient did not remember falling and the son was not able to provide details about the nature or circumstances of the fall. The patient reported no pain in his abdomen, arms, legs, or groin and no headache.
The patient had a history of hypertension. During a previous evaluation for cough, he was reportedly told that he had a lung disease that had ""caused the lung tissue to harden."" Before the onset of his most recent symptoms, he had walked outside on a daily basis without limitation from shortness of breath. He took an unknown medication for hypertension. The patient did not smoke tobacco, use illicit drugs, or drink alcohol. He lived in an apartment with his wife.
On examination, the temperature was 37.9[degrees]C, the blood pressure 157/95 mm Hg, the pulse 112 beats per minute, the respiratory rate 30 breaths per minute, and the oxygen saturation 91% while the patient was breathing ambient air. The respiratory rate decreased to 28 breaths per minute and the oxygen saturation improved to 96% with the administration of supplemental oxygen through a nasal cannula at a rate of 4 liters per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 22.8. Retractions were noted in the supraclavicular areas. Inspiratory crackles could be heard at the lung bases. The heart sounds were regular, with tachycardia but no murmur. There was no tenderness on palpation of the chest wall and no edema in the legs. Laboratory test results are shown in Table 1.	
Table 1 
Dr. Reece J. Goiffon: A single-view portable anteroposterior radiograph of the chest showed bilateral patchy airspace opacities that were more extensive in the left lung than in the right lung, with predominance in the peripheral lower lung zones and with relative sparing of the perihilar regions (Figure 1). These opacities were superimposed on mild apical and bibasilar bronchiectasis and bibasilar reticular opacities. A radiograph of the pelvis showed no fracture.	
Figure 1 
Dr. Emmett: An electrocardiogram showed sinus tachycardia. Blood samples were obtained for culture, and a nasopharyngeal swab was submitted to test for SARS-CoV-2 RNA. Azithromycin and ceftriaxone were administered, and the patient was admitted to the hospital.
On arrival at the medical floor, the patient was in respiratory distress, with a respiratory rate of 40 breaths per minute and an oxygen saturation of 86% while he was receiving supplemental oxygen through a nasal cannula at a rate of 4 liters per minute. The patient was restless and appeared uncomfortable, moving around in the bed and attempting to sit up; he reported severe pleuritic chest pain. The oxygen flow rate was adjusted to 5 liters per minute, and morphine was administered intravenously. A repeat electrocardiogram showed sinus tachycardia.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 81-year-old man was admitted to this hospital with fever, cough, and shortness of breath during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient had been in his usual state of health until 3 days before this admission, when fever and cough developed. On the morning of admission, he noted an abrupt onset of shortness of breath at rest and dyspnea on exertion. There was also substernal chest pain on the left side that worsened with deep breaths and when he lay down. The patient's son called emergency medical services, and the patient was brought to the emergency department of this hospital for further evaluation.
On arrival at the emergency department, the patient described ongoing chest pain and shortness of breath. The son reported that the patient had fallen at home 2 days before admission, but the patient did not remember falling and the son was not able to provide details about the nature or circumstances of the fall. The patient reported no pain in his abdomen, arms, legs, or groin and no headache.
The patient had a history of hypertension. During a previous evaluation for cough, he was reportedly told that he had a lung disease that had ""caused the lung tissue to harden."" Before the onset of his most recent symptoms, he had walked outside on a daily basis without limitation from shortness of breath. He took an unknown medication for hypertension. The patient did not smoke tobacco, use illicit drugs, or drink alcohol. He lived in an apartment with his wife.
On examination, the temperature was 37.9[degrees]C, the blood pressure 157/95 mm Hg, the pulse 112 beats per minute, the respiratory rate 30 breaths per minute, and the oxygen saturation 91% while the patient was breathing ambient air. The respiratory rate decreased to 28 breaths per minute and the oxygen saturation improved to 96% with the administration of supplemental oxygen through a nasal cannula at a rate of 4 liters per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 22.8. Retractions were noted in the supraclavicular areas. Inspiratory crackles could be heard at the lung bases. The heart sounds were regular, with tachycardia but no murmur. There was no tenderness on palpation of the chest wall and no edema in the legs. Laboratory test results are shown in Table 1.	
Table 1 
Dr. Reece J. Goiffon: A single-view portable anteroposterior radiograph of the chest showed bilateral patchy airspace opacities that were more extensive in the left lung than in the right lung, with predominance in the peripheral lower lung zones and with relative sparing of the perihilar regions (Figure 1). These opacities were superimposed on mild apical and bibasilar bronchiectasis and bibasilar reticular opacities. A radiograph of the pelvis showed no fracture.	
Figure 1 
Dr. Emmett: An electrocardiogram showed sinus tachycardia. Blood samples were obtained for culture, and a nasopharyngeal swab was submitted to test for SARS-CoV-2 RNA. Azithromycin and ceftriaxone were administered, and the patient was admitted to the hospital.
On arrival at the medical floor, the patient was in respiratory distress, with a respiratory rate of 40 breaths per minute and an oxygen saturation of 86% while he was receiving supplemental oxygen through a nasal cannula at a rate of 4 liters per minute. The patient was restless and appeared uncomfortable, moving around in the bed and attempting to sit up; he reported severe pleuritic chest pain. The oxygen flow rate was adjusted to 5 liters per minute, and morphine was administered intravenously. A repeat electrocardiogram showed sinus tachycardia.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with fever, cough, and shortness of breath during the Covid-19 pandemic. These symptoms are consistent with a Covid-19 infection. The patient's chest radiograph showed bilateral patchy airspace opacities, which is a common finding in Covid-19 pneumonia. The patient's condition worsened upon arrival at the medical floor, with increased respiratory distress and severe pleuritic chest pain. A nasopharyngeal swab was submitted to test for SARS-CoV-2 RNA, which is the virus that causes Covid-19. \n\nCOVID-19 (SARS-CoV-2 infection)""
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        ""content"": ""The patient is an elderly man presenting with fever, cough, and shortness of breath during the COVID-19 pandemic. He also has substernal chest pain that worsens with deep breaths and when lying down. The differential diagnosis for this patient includes COVID-19, bacterial pneumonia, pulmonary embolism, and acute coronary syndrome. The patient's history of hypertension and lung disease that \""caused the lung tissue to harden\"" could suggest chronic obstructive pulmonary disease (COPD) or interstitial lung disease, which could predispose him to bacterial pneumonia. However, his symptoms started abruptly, which is more characteristic of a viral infection or a pulmonary embolism. The patient's chest pain could suggest acute coronary syndrome, but it is pleuritic in nature, which is more consistent with a respiratory cause. The patient's chest radiograph shows bilateral patchy airspace opacities, which is a common finding in COVID-19. His nasopharyngeal swab was also submitted for SARS-CoV-2 RNA testing. Given the patient's symptoms, the current pandemic, and his chest radiograph findings, COVID-19 is the most likely diagnosis.\n\nDiagnosis: COVID-19.""
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10.1056/NEJMcpc2100281,"Case 17-2021: An 82-Year-Old Woman with Pain, Swelling, and Ecchymosis of the Left Arm","Hematocrit (%) 34–45 33.7   31.1
Hemoglobin (g/dl) 11–16 10.9   10.5
White-cell count (per μl) 400 ,000 8000   9170
Differential count (%)
Neutrophils 40–75 66   66
Lymphocytes 15–54 21   21
Monocytes 4–13 10   10
Eosinophils 0–7 2   2
Basophils 0–1 0.6   0.6
Platelet count (per μl)   280,000   294,000
Mean corpuscular volume (fl) 8  88.2   84.7
Lactic acid (mmol/liter)† — —   2.4
Creatine kinase (U/liter) — —   207
Prothrombin time (sec) 9.6–12.3 12.5   13.3
International normalized ratio   1.1   1.0
Activated partial-thromboplastin time 
(sec)
— — 22–36 72.4
d-Dimer (ng/ml) — —   2515
Fibrinogen (mg/dl) — — 15 0 470",Acquired factor VIII inhibitor,Acquired factor VIII inhibitor.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 82-year-old woman was admitted to this hospital with pain, swelling, and ecchymosis of the left arm.
The patient had been in her usual state of health until 4 days before admission, when she awoke from sleep with swelling and discoloration of the skin of the left arm above the elbow. There was no history of trauma to the arm. Over the next 2 days, the swelling and discoloration spread to the elbow and forearm and pain developed. The patient presented to the emergency department of another hospital for evaluation.
On examination, the temperature was 36.9[degrees]C, the blood pressure 153/65 mm Hg, the pulse 59 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. Ecchymosis extended from above the left elbow to the left wrist, and there was pain with palpation of the left forearm. The radial pulse was normal, as was range of motion in the left elbow and wrist. Radiographs of the left forearm showed diffuse osteopenia and degenerative changes of the wrist joint, without fractures or bone lesions. Blood levels of electrolytes and glucose were normal, as were results of kidney-function tests; other laboratory test results are shown in Table 1. Ibuprofen was administered, and the patient was given a shoulder sling for comfort and discharged home.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Over the next 2 days, the pain in the left arm worsened and the ecchymosis spread to the left hand and digits. The pain did not abate with the use of ice packs or acetaminophen or with elevation of the arm. The patient presented to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported pain in the left arm that occurred with supination or while she was making a fist. There was no numbness or tingling in the arm or hand or history of hemarthrosis, prolonged bleeding with dental procedures, or menorrhagia. The medical history was notable for hypertension, dyslipidemia, peripheral vascular disease, carotid artery stenosis, osteoporosis, chronic kidney disease, and obesity, as well as an episode of deep venous thrombosis 40 years earlier. Medications included aspirin, atorvastatin, lisinopril, hydrochlorothiazide, and metoprolol. The patient had smoked tobacco for 40 years but had quit 22 years earlier. She did not drink alcohol or use illicit drugs. She was widowed and lived alone but visited with her grown children regularly. Her father had had coronary artery disease.
On examination, the temperature was 36.1[degrees]C, the blood pressure 169/77 mm Hg, the pulse 76 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 72.5 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 32.3. There was discoloration of the left arm with sharp demarcation in the middle of the upper arm, proximal to the elbow, and uniform extension to the metacarpophalangeal joints (Figure 1). There was tenderness with palpation of the forearm and dorsal wrist, passive range of motion of the wrist and elbow, and diffuse swelling and mild firmness of the forearm, without induration. Sensation to light touch was intact throughout the arm and hand. The radial pulse was normal, and the fingers were warm, with brisk capillary refill in all the digits. The remainder of the physical examination was normal. Blood levels of electrolytes and glucose were normal, as were results of kidney- and liver-function tests; other laboratory test results are shown in Table 1.	
Figure 1 
Dr. Patrick D. Sutphin: Computed tomography (CT) of the left arm, performed after the administration of intravenous contrast material, revealed disproportionate enlargement of the brachioradialis muscle, a finding suggestive of intramuscular hematoma. There was hyperdense stranding in the subcutaneous fat centered over the elbow and forearm, a finding consistent with hemorrhage (Figure 2). CT angiography of the arteries revealed heavy, partially calcified plaque throughout the thoracic aorta. Focal heavy plaque in the left subclavian artery proximal to the vertebral artery resulted in approximately 70 to 80% stenosis (Figure 3). The arteries in the left arm were otherwise patent. There were no signs of active hemorrhage on arterial or delayed-phase images or findings that could lead to localization of an arterial injury, such as pseudoaneurysm or dissection. In addition, an enhancing mass was not identified. The visualized superficial and deep veins were patent on delayed-phase images.	
Figure 2 
Dr. Sridharan: A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 82-year-old woman was admitted to this hospital with pain, swelling, and ecchymosis of the left arm.
The patient had been in her usual state of health until 4 days before admission, when she awoke from sleep with swelling and discoloration of the skin of the left arm above the elbow. There was no history of trauma to the arm. Over the next 2 days, the swelling and discoloration spread to the elbow and forearm and pain developed. The patient presented to the emergency department of another hospital for evaluation.
On examination, the temperature was 36.9[degrees]C, the blood pressure 153/65 mm Hg, the pulse 59 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. Ecchymosis extended from above the left elbow to the left wrist, and there was pain with palpation of the left forearm. The radial pulse was normal, as was range of motion in the left elbow and wrist. Radiographs of the left forearm showed diffuse osteopenia and degenerative changes of the wrist joint, without fractures or bone lesions. Blood levels of electrolytes and glucose were normal, as were results of kidney-function tests; other laboratory test results are shown in Table 1. Ibuprofen was administered, and the patient was given a shoulder sling for comfort and discharged home.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Over the next 2 days, the pain in the left arm worsened and the ecchymosis spread to the left hand and digits. The pain did not abate with the use of ice packs or acetaminophen or with elevation of the arm. The patient presented to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported pain in the left arm that occurred with supination or while she was making a fist. There was no numbness or tingling in the arm or hand or history of hemarthrosis, prolonged bleeding with dental procedures, or menorrhagia. The medical history was notable for hypertension, dyslipidemia, peripheral vascular disease, carotid artery stenosis, osteoporosis, chronic kidney disease, and obesity, as well as an episode of deep venous thrombosis 40 years earlier. Medications included aspirin, atorvastatin, lisinopril, hydrochlorothiazide, and metoprolol. The patient had smoked tobacco for 40 years but had quit 22 years earlier. She did not drink alcohol or use illicit drugs. She was widowed and lived alone but visited with her grown children regularly. Her father had had coronary artery disease.
On examination, the temperature was 36.1[degrees]C, the blood pressure 169/77 mm Hg, the pulse 76 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 72.5 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 32.3. There was discoloration of the left arm with sharp demarcation in the middle of the upper arm, proximal to the elbow, and uniform extension to the metacarpophalangeal joints (Figure 1). There was tenderness with palpation of the forearm and dorsal wrist, passive range of motion of the wrist and elbow, and diffuse swelling and mild firmness of the forearm, without induration. Sensation to light touch was intact throughout the arm and hand. The radial pulse was normal, and the fingers were warm, with brisk capillary refill in all the digits. The remainder of the physical examination was normal. Blood levels of electrolytes and glucose were normal, as were results of kidney- and liver-function tests; other laboratory test results are shown in Table 1.	
Figure 1 
Dr. Patrick D. Sutphin: Computed tomography (CT) of the left arm, performed after the administration of intravenous contrast material, revealed disproportionate enlargement of the brachioradialis muscle, a finding suggestive of intramuscular hematoma. There was hyperdense stranding in the subcutaneous fat centered over the elbow and forearm, a finding consistent with hemorrhage (Figure 2). CT angiography of the arteries revealed heavy, partially calcified plaque throughout the thoracic aorta. Focal heavy plaque in the left subclavian artery proximal to the vertebral artery resulted in approximately 70 to 80% stenosis (Figure 3). The arteries in the left arm were otherwise patent. There were no signs of active hemorrhage on arterial or delayed-phase images or findings that could lead to localization of an arterial injury, such as pseudoaneurysm or dissection. In addition, an enhancing mass was not identified. The visualized superficial and deep veins were patent on delayed-phase images.	
Figure 2 
Dr. Sridharan: A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Spontaneous Hematoma due to anticoagulation. The patient's history of taking aspirin, a blood thinner, combined with the CT scan showing an intramuscular hematoma and hemorrhage in the subcutaneous fat, suggest that the patient experienced a spontaneous hematoma. The patient's age and history of peripheral vascular disease and deep venous thrombosis also increase her risk for such an event.""
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        ""content"": ""The patient is an elderly woman with a history of peripheral vascular disease and carotid artery stenosis who presented with pain, swelling, and ecchymosis of the left arm. The ecchymosis extended from above the elbow to the wrist and later spread to the hand and digits. There was no history of trauma, and radiographs of the forearm showed no fractures or bone lesions. CT angiography revealed heavy plaque in the left subclavian artery resulting in significant stenosis, but no signs of active hemorrhage or arterial injury. The patient's symptoms and imaging findings are consistent with spontaneous hematoma, likely secondary to her vascular disease and anticoagulant use.\n\nDiagnosis: Spontaneous Hematoma.""
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        ""content"": ""The patient is an elderly woman who presents with pain, swelling, and ecchymosis of the left arm. She has no history of trauma to the arm. The differential diagnosis for this patient includes deep vein thrombosis, hematoma, cellulitis, and compartment syndrome. The patient has a history of deep vein thrombosis, but her symptoms are not consistent with this condition. She does not have a fever or other signs of infection, making cellulitis less likely. Compartment syndrome typically presents with severe pain and sensory deficits, which the patient does not have. The patient's CT scan shows enlargement of the brachioradialis muscle, suggestive of an intramuscular hematoma. This, along with the patient's history of anticoagulant use, makes hematoma the most likely diagnosis.\n\nDiagnosis: Intramuscular Hematoma.""
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10.1056/NEJMcpc2100278,Case 16-2021: A 37-Year-Old Woman with Abdominal Pain and Aortic Dilatation,"White-cell count (per μl) 4800–10,000 9800 32,800   27,710
Differential count (per μl)
Neutrophils 190 000 6958 30,832   22,260
Lymphocytes   1372 1312   1950
Monocytes   1176 1312   2340
Eosinophils   98 0   30
Platelet count (per μl)   289,000 565,000   576,000
Hemoglobin (g/dl)   12.3 11.1   13.5
Hematocrit (%) 37.0–47.0 38.5 34.2   42.1
Erythrocyte sedimentation rate (mm/hr)  0 41 18  0 57
C-reactive protein (mg/liter) 0.0–10.0 44.0 110.0 0. .0 60.6
Lactic acid (mmol/liter)   0.6 1.4   1.2
Alanine aminotransferase (U/liter) 7–40 18 28   27
Aspartate aminotransferase (U/liter) 13–40 7 11   18
Alkaline phosphatase (U/liter) 46–116 70 84   107
Sodium (mmol/liter)   138 133   133
Potassium (mmol/liter) 3.5–5.1 3.2 4.4   4.2
Chloride (mmol/liter) 98–107 105 104   95
Carbon dioxide (mmol/liter) 2 1 27 29   26
Urea nitrogen (mg/dl) 9–23 9 11   11
Creatinine (mg/dl) 0.50–0.80 0.73 0.63   0.78
Glucose (mg/dl) 74–100 104 137   99",Staphylococcus aureus bacteremia and infection of a vascular graft.,"Mycotic aneurysm, potentially in the context of underlying vascular injury or vasculitis.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 37-year-old woman was transferred to this hospital because of abdominal pain and aortic dilatation.
The patient had been well until 3 weeks before the current admission, when she began to have pain in the right side of the abdomen that radiated to the back. She also had nausea, vomiting, fever, and chills. Approximately 2 weeks before the current admission, she sought evaluation at the emergency department of another hospital. Physical examination was notable for pain with palpation of all four quadrants. The pulses were normal, and the blood pressure did not differ substantially between the two arms or between the two legs. The white-cell count was 9800 per microliter (reference range at the other hospital, 4800 to 10,000), the erythrocyte sedimentation rate 41 mm per hour (reference range, 0 to 20), and the C-reactive protein level 44.0 mg per liter (reference range, 0 to 10.0). Other laboratory test results are shown in Table 1. Blood specimens were obtained for two sets of bacterial cultures, with each set consisting of an aerobic bottle and an anaerobic bottle.	
Table 1 
Dr. Patrick D. Sutphin: Computed tomography (CT) of the abdomen and pelvis, performed without the intravenous administration of contrast material, revealed soft-tissue density adjacent to the infrarenal abdominal aorta and mild-to-moderate associated periaortic fat stranding (Figure 1A and 1B). These findings prompted CT angiography, performed 1 hour later, which more clearly delineated infrarenal abdominal aortic wall thickening at the level of the inferior mesenteric artery, with an aortic diameter of 2.3 cm (Figure 1C).	
Figure 1 
Dr. Tanious: The patient was discharged from the emergency department of the other hospital on the same day, with a referral to the rheumatology clinic of that hospital and instructions to start treatment with prednisone. One day after discharge, one of the four culture bottles grew gram-positive bacilli, and the patient was admitted to the other hospital for investigation. After an evaluation, the positive culture was presumed to be contaminated. Additional blood specimens were obtained for culture, and the patient was discharged home on the second hospital day.
The fever and chills resolved, and the abdominal pain abated initially but then gradually worsened. Eight days after discharge and 3 days before the current admission, the patient returned to the emergency department of the other hospital. On examination, the temperature was 36.8[degrees]C, the pulse 50 beats per minute, and the blood pressure 146/78 mm Hg. Physical examination was notable for diffuse abdominal tenderness, which was worse with deep palpation in all four quadrants. The white-cell count was 32,800 per microliter, the platelet count 565,000 per microliter (reference range, 140,000 to 440,000), the erythrocyte sedimentation rate 18 mm per hour, and the C-reactive protein level 110.0 mg per liter. The urinalysis was normal; urine toxicologic screening was positive for amphetamines, cannabinoids, and opiates. Other laboratory test results are shown in Table 1.
Dr. Sutphin: CT angiography revealed progression of aortic wall thickening and periaortic fat stranding and interval narrowing of the proximal segment of the inferior mesenteric artery, with an increase in the aortic diameter to 3.1 cm.
Dr. Tanious: The patient was admitted to the other hospital for a second time. Intravenous fluids, methylprednisolone, and heparin were administered, as was empirical treatment with vancomycin and piperacillin-tazobactam. During the next 3 days, the patient remained afebrile. Consultations with the rheumatology, infectious diseases, and vascular surgery departments were requested.
Dr. Sutphin: On the second hospital day, magnetic resonance angiography of the abdomen revealed an increase in aneurysmal dilatation of the infrarenal abdominal aorta (aortic diameter, 3.6 cm) with enhancement of the aortic wall. On the fourth hospital day, CT angiography of the abdomen and pelvis revealed a further increase in aneurysmal dilatation of the infrarenal abdominal aorta (aortic diameter, 3.9 cm) with increasing luminal irregularity and periaortic fat stranding.
Dr. Tanious: The patient was transferred to this hospital for additional treatment. On evaluation, she reported abdominal pain that was worst in the right upper quadrant and radiated to the right lower quadrant, back, and chest. She rated the pain as 10 on a scale of 0 to 10, with 10 indicating the most severe pain. She also reported nausea but had not had fevers or chills since before the initial presentation. A review of systems was notable for the absence of fatigue, weight loss, night sweats, myalgias, joint pain, and rash; blue fingertips occurred with exposure to cold.
Dr. Sutphin: CT angiography of the abdomen and pelvis revealed evidence of continued aneurysmal enlargement and increased luminal irregularity (Figure 1D, 1E, and 1F).
Dr. Tanious: The patient had a history of polycystic ovary syndrome, depression, post-traumatic stress disorder, attention deficit-hyperactivity disorder, asthma, and Chiari I malformation, which had led to suboccipital craniectomy 3 years earlier. She had undergone cesarean section 5 years earlier. Medications included prednisone, clonidine, promethazine, dicyclomine, and inhaled albuterol; latex had caused a rash. The patient was White, lived in an urban area of New England, and had recently been homeless. She had injected heroin for the past 5 years; her last injection had been 3 weeks earlier. She had a history of marijuana use and reported no methamphetamine use. Sexual history was not obtained. She drank four alcoholic beverages and smoked one pack of cigarettes daily. Her sister had rheumatoid arthritis, her grandmother had tuberculosis, and several family members had hypermobility of the joints.
On examination, the patient was uncomfortable because of the abdominal pain. The abdomen was soft, with diffuse tenderness that was worst in the right upper quadrant and both lower quadrants. She did not have any ulcers, rash, lymphadenopathy, or warmth, redness, or swelling of the joints; the elbows and metacarpophalangeal joints were hyperextensible. The white-cell count was 27,710 per microliter (reference range at this hospital, 4500 to 11,000), the platelet count 576,000 per microliter (reference range, 150,000 to 400,000), the erythrocyte sedimentation rate 57 mm per hour (reference range, 0 to 20), and the C-reactive protein level 60.6 mg per liter (reference range, 0 to 8.0). Testing for human immunodeficiency virus types 1 and 2 was negative. Serologic testing for hepatitis C virus was positive. The blood-culture isolate detected at the other hospital was identified as bacillus species, and all other blood cultures performed at the other hospital showed no growth. Other laboratory test results are shown in Table 1.
Management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 37-year-old woman was transferred to this hospital because of abdominal pain and aortic dilatation.
The patient had been well until 3 weeks before the current admission, when she began to have pain in the right side of the abdomen that radiated to the back. She also had nausea, vomiting, fever, and chills. Approximately 2 weeks before the current admission, she sought evaluation at the emergency department of another hospital. Physical examination was notable for pain with palpation of all four quadrants. The pulses were normal, and the blood pressure did not differ substantially between the two arms or between the two legs. The white-cell count was 9800 per microliter (reference range at the other hospital, 4800 to 10,000), the erythrocyte sedimentation rate 41 mm per hour (reference range, 0 to 20), and the C-reactive protein level 44.0 mg per liter (reference range, 0 to 10.0). Other laboratory test results are shown in Table 1. Blood specimens were obtained for two sets of bacterial cultures, with each set consisting of an aerobic bottle and an anaerobic bottle.	
Table 1 
Dr. Patrick D. Sutphin: Computed tomography (CT) of the abdomen and pelvis, performed without the intravenous administration of contrast material, revealed soft-tissue density adjacent to the infrarenal abdominal aorta and mild-to-moderate associated periaortic fat stranding (Figure 1A and 1B). These findings prompted CT angiography, performed 1 hour later, which more clearly delineated infrarenal abdominal aortic wall thickening at the level of the inferior mesenteric artery, with an aortic diameter of 2.3 cm (Figure 1C).	
Figure 1 
Dr. Tanious: The patient was discharged from the emergency department of the other hospital on the same day, with a referral to the rheumatology clinic of that hospital and instructions to start treatment with prednisone. One day after discharge, one of the four culture bottles grew gram-positive bacilli, and the patient was admitted to the other hospital for investigation. After an evaluation, the positive culture was presumed to be contaminated. Additional blood specimens were obtained for culture, and the patient was discharged home on the second hospital day.
The fever and chills resolved, and the abdominal pain abated initially but then gradually worsened. Eight days after discharge and 3 days before the current admission, the patient returned to the emergency department of the other hospital. On examination, the temperature was 36.8[degrees]C, the pulse 50 beats per minute, and the blood pressure 146/78 mm Hg. Physical examination was notable for diffuse abdominal tenderness, which was worse with deep palpation in all four quadrants. The white-cell count was 32,800 per microliter, the platelet count 565,000 per microliter (reference range, 140,000 to 440,000), the erythrocyte sedimentation rate 18 mm per hour, and the C-reactive protein level 110.0 mg per liter. The urinalysis was normal; urine toxicologic screening was positive for amphetamines, cannabinoids, and opiates. Other laboratory test results are shown in Table 1.
Dr. Sutphin: CT angiography revealed progression of aortic wall thickening and periaortic fat stranding and interval narrowing of the proximal segment of the inferior mesenteric artery, with an increase in the aortic diameter to 3.1 cm.
Dr. Tanious: The patient was admitted to the other hospital for a second time. Intravenous fluids, methylprednisolone, and heparin were administered, as was empirical treatment with vancomycin and piperacillin-tazobactam. During the next 3 days, the patient remained afebrile. Consultations with the rheumatology, infectious diseases, and vascular surgery departments were requested.
Dr. Sutphin: On the second hospital day, magnetic resonance angiography of the abdomen revealed an increase in aneurysmal dilatation of the infrarenal abdominal aorta (aortic diameter, 3.6 cm) with enhancement of the aortic wall. On the fourth hospital day, CT angiography of the abdomen and pelvis revealed a further increase in aneurysmal dilatation of the infrarenal abdominal aorta (aortic diameter, 3.9 cm) with increasing luminal irregularity and periaortic fat stranding.
Dr. Tanious: The patient was transferred to this hospital for additional treatment. On evaluation, she reported abdominal pain that was worst in the right upper quadrant and radiated to the right lower quadrant, back, and chest. She rated the pain as 10 on a scale of 0 to 10, with 10 indicating the most severe pain. She also reported nausea but had not had fevers or chills since before the initial presentation. A review of systems was notable for the absence of fatigue, weight loss, night sweats, myalgias, joint pain, and rash; blue fingertips occurred with exposure to cold.
Dr. Sutphin: CT angiography of the abdomen and pelvis revealed evidence of continued aneurysmal enlargement and increased luminal irregularity (Figure 1D, 1E, and 1F).
Dr. Tanious: The patient had a history of polycystic ovary syndrome, depression, post-traumatic stress disorder, attention deficit-hyperactivity disorder, asthma, and Chiari I malformation, which had led to suboccipital craniectomy 3 years earlier. She had undergone cesarean section 5 years earlier. Medications included prednisone, clonidine, promethazine, dicyclomine, and inhaled albuterol; latex had caused a rash. The patient was White, lived in an urban area of New England, and had recently been homeless. She had injected heroin for the past 5 years; her last injection had been 3 weeks earlier. She had a history of marijuana use and reported no methamphetamine use. Sexual history was not obtained. She drank four alcoholic beverages and smoked one pack of cigarettes daily. Her sister had rheumatoid arthritis, her grandmother had tuberculosis, and several family members had hypermobility of the joints.
On examination, the patient was uncomfortable because of the abdominal pain. The abdomen was soft, with diffuse tenderness that was worst in the right upper quadrant and both lower quadrants. She did not have any ulcers, rash, lymphadenopathy, or warmth, redness, or swelling of the joints; the elbows and metacarpophalangeal joints were hyperextensible. The white-cell count was 27,710 per microliter (reference range at this hospital, 4500 to 11,000), the platelet count 576,000 per microliter (reference range, 150,000 to 400,000), the erythrocyte sedimentation rate 57 mm per hour (reference range, 0 to 20), and the C-reactive protein level 60.6 mg per liter (reference range, 0 to 8.0). Testing for human immunodeficiency virus types 1 and 2 was negative. Serologic testing for hepatitis C virus was positive. The blood-culture isolate detected at the other hospital was identified as bacillus species, and all other blood cultures performed at the other hospital showed no growth. Other laboratory test results are shown in Table 1.
Management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of abdominal pain, nausea, vomiting, fever, and chills, along with the CT findings of aortic wall thickening and periaortic fat stranding, suggest an inflammatory process involving the aorta. The increase in aortic diameter over time indicates an aneurysmal dilatation. The patient's history of drug use, particularly intravenous heroin, raises the possibility of an infectious cause. However, the blood cultures were negative, and the patient did not respond to antibiotics, suggesting a non-infectious cause. The patient's elevated inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) further support an inflammatory process. The patient's hyperextensible joints suggest a connective tissue disorder, which can be associated with aortitis and aneurysm formation. Taken together, these findings suggest a diagnosis of non-infectious aortitis, possibly secondary to a connective tissue disorder.\n\nDiagnosis: Non-infectious aortitis secondary to a connective tissue disorder.""
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        ""content"": ""This is a 37-year-old woman with a history of drug use who presents with abdominal pain, aortic dilatation, and a high white blood cell count. The differential diagnosis includes aortic aneurysm, aortic dissection, vasculitis, and infectious aortitis. The patient's history of drug use and positive hepatitis C test could suggest an infectious cause. However, the blood cultures were negative, making infectious aortitis less likely. The rapid progression of the aortic dilatation and the patient's high inflammatory markers could suggest an inflammatory process such as vasculitis. However, the patient does not have other symptoms typically associated with vasculitis such as rash, joint pain, or myalgias. Aortic aneurysm or dissection could also cause the patient's symptoms. However, these conditions typically do not cause such a high white blood cell count or such high inflammatory markers. Given the patient's rapid aortic dilatation, high inflammatory markers, and lack of other symptoms, the most likely diagnosis is non-infectious inflammatory aortitis.\n\nDiagnosis: Non-infectious inflammatory aortitis.""
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10.1056/NEJMcpc2100274,"Case 15-2021: A 76-Year-Old Woman with Nausea, Diarrhea, and Acute Kidney Failure","Hemoglobin (g/dl)   10.8 10.8 10.4
Hematocrit (%)   32.6 32.6 31.7
Mean corpuscular volume (fl)   94.8 94.8 93.2
White-cell count (per μl) 4.5–11.0 7.9 7.90 8.48
Differential count (per μl)
Neutrophils 1.8–7.7 3.1 5.33 5.84
Immature granulocytes 0–0.10 0.05 0.09 0.02
Lymphocytes 1.0–4.8 2.46 1.59 1.55
Eosinophils 0–0.9 0.34 0.23 0.27
Basophils 0–0.3 0.04 0.03 0.03
Monocytes 0.2–1.2 0.68 0.63 0.77
Platelet count (per μl)   265,000 265,000 238,000
Sodium (mmol/liter)   136 138 131
Potassium (mmol/liter)   4.4 4.4 4.7
Chloride (mmol/liter)   96 97 80
Carbon dioxide (mmol/liter)   26 25 22
Anion gap (mmol/liter)   14 16 29
Glucose (mg/dl)   141 126 51
Creatinine (mg/dl)   1.88 1.71 7.66
Urea nitrogen (mg/dl)   38 51 138
Aspartate aminotransferase (U/liter)   28 35 41
Alanine aminotransferase (U/liter)   28 54 52
Alkaline phosphatase (U/liter)   58 68 113
Total bilirubin (mg/dl)  0.4 0.4 0.4
Direct bilirubin (mg/dl) 0.  <0.2 <0.2 <0.2
Albumin (g/dl)   3.9 4.3 4.2
Lactic acid (mmol/liter)   — — 7.4
Lipase (U/liter) 13–60 — — 86
Phosphorus (mg/dl)   — — 6.6
High-sensitivity troponin T (ng/liter) 0–9 — 28 69
N-terminal pro–B-type natriuretic pep‑
tide (pg/ml)
0–1800 1349 — 5935
Prothrombin-time international nor‚Äë
malized ratio
  — — 3.5
Arterial blood gases — —
pH   — — 7.17
Partial pressure of carbon dioxide 
(mm Hg)
  — — 57
Partial pressure of oxygen (mm Hg)   — — 70
Bicarbonate (mmol/liter) 24–30 — — 20
SARS-CoV-2 RNA PCR test of nasopha‚Äë
ryngeal swab
Negative Negative Negative Negative                                                                              Urine sodium (mmol/liter) — — — 42
Urine creatinine (mg/dl) — — — 65             ",Lactic acidosis due to toxic effects from metfor min use,Toxic effects from metformin use in the context of acute tubular necrosis from diuretic use.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old woman with heart failure and type 2 diabetes mellitus was admitted to this hospital with nausea, diarrhea, and acute kidney failure.
The patient normally lived independently, but she had been staying in a skilled nursing facility for the past several weeks to recover from a recent humeral fracture. During her stay, nausea, abdominal cramps, and nonbloody diarrhea developed. The next day, the symptoms persisted, and she was transferred to the emergency department of this hospital.
Approximately 3 months before the current admission, the patient was admitted to this hospital with respiratory failure due to an exacerbation of heart failure and pneumonia. She was treated with intravenous ceftriaxone and oral doxycycline for 5 days, and diuretic agents were adjusted during a 3-week hospitalization. Nine weeks before the current admission, the patient's condition returned to baseline, and she was discharged home with instructions to continue a diuretic regimen of torsemide and spironolactone. The patient's dry weight was 127 kg. Laboratory test results at the time of discharge are shown in Table 1.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Four weeks before the current admission, the patient lost her balance while walking and fell onto her right side. She had no loss of consciousness, chest pain, or other symptoms. She was evaluated in the emergency department of this hospital and reported pain in her right arm. On examination, there were abrasions and bruising over the right elbow, with tenderness on palpation; the weight was 123 kg. The right radial pulse was normal, and sensation was intact in the arm and hand. Laboratory test results are shown in Table 1. Radiography of the right arm showed a mild transcondylar fracture of the right distal humerus. A splint was placed, and the patient was advised not to bear weight with the right arm. She was discharged to a skilled nursing facility for increased support with daily activities while she was recovering.
Two weeks before the current admission, while the patient was staying in the skilled nursing facility, edema developed in both legs, and her weight increased by 5 kg. She attributed the weight gain to increased salt intake. Nine days before the current admission, oral metolazone was added to her diuretic regimen, and the leg edema resolved.
At the time of the current admission, the patient reported nausea and abdominal cramps. She reported no fever, chills, cough, dyspnea, dysuria, flank pain, or vomiting. She had no known sick contacts. Her medical history included hypertension, atrial fibrillation, coronary artery disease, heart failure with reduced ejection fraction, type 2 diabetes mellitus, and obstructive sleep apnea, for which nightly treatment with continuous positive airway pressure had been prescribed. Medications included allopurinol, amiodarone, aspirin, atorvastatin, cyclobenzaprine, enoxaparin, fluticasone, glipizide, loratadine, lorazepam, metformin, metolazone, metoprolol, sertraline, spironolactone, torsemide, warfarin, and zolpidem. The last doses of metolazone, spironolactone, and torsemide were taken more than 24 hours before admission. There were no known drug allergies. Before the recent humeral fracture, the patient had been living alone in an urban area of New England; she required assistance from home health services for bathing and chores and used a walker for ambulation. She did not smoke tobacco or drink alcohol. She had no recent history of travel, and her family history was unremarkable.
On examination, the patient appeared well, without respiratory distress. The temperature was 36.7[degrees]C, the blood pressure 137/63 mm Hg, the heart rate 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. The weight was 126 kg. The oral mucous membranes were dry. The heart sounds were normal, as were the breath sounds throughout both lung fields. There was no edema in the lower legs. The right arm was in a splint.
The blood level of creatinine was 7.66 mg per deciliter (677 [mu]mol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 [mu]mol per liter]), and the level of lactic acid was 7.4 mmol per liter (67 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter [4.5 to 18 mg per deciliter]). Urinalysis by dipstick showed a pH of 5.0 (reference range, 5.0 to 9.0) and a specific gravity of 1.012 (reference range, 1.001 to 1.035), and no protein, blood, nitrites, leukocyte esterase, glucose, or ketones were present. Additional laboratory test results are shown in Table 1.
Chest radiography revealed mild pulmonary interstitial edema. Ultrasonography of the kidneys and urinary tract revealed simple cysts in the left kidney, with no evidence of hydronephrosis or nephrolithiasis.
Intravenous fluids were administered, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old woman with heart failure and type 2 diabetes mellitus was admitted to this hospital with nausea, diarrhea, and acute kidney failure.
The patient normally lived independently, but she had been staying in a skilled nursing facility for the past several weeks to recover from a recent humeral fracture. During her stay, nausea, abdominal cramps, and nonbloody diarrhea developed. The next day, the symptoms persisted, and she was transferred to the emergency department of this hospital.
Approximately 3 months before the current admission, the patient was admitted to this hospital with respiratory failure due to an exacerbation of heart failure and pneumonia. She was treated with intravenous ceftriaxone and oral doxycycline for 5 days, and diuretic agents were adjusted during a 3-week hospitalization. Nine weeks before the current admission, the patient's condition returned to baseline, and she was discharged home with instructions to continue a diuretic regimen of torsemide and spironolactone. The patient's dry weight was 127 kg. Laboratory test results at the time of discharge are shown in Table 1.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Four weeks before the current admission, the patient lost her balance while walking and fell onto her right side. She had no loss of consciousness, chest pain, or other symptoms. She was evaluated in the emergency department of this hospital and reported pain in her right arm. On examination, there were abrasions and bruising over the right elbow, with tenderness on palpation; the weight was 123 kg. The right radial pulse was normal, and sensation was intact in the arm and hand. Laboratory test results are shown in Table 1. Radiography of the right arm showed a mild transcondylar fracture of the right distal humerus. A splint was placed, and the patient was advised not to bear weight with the right arm. She was discharged to a skilled nursing facility for increased support with daily activities while she was recovering.
Two weeks before the current admission, while the patient was staying in the skilled nursing facility, edema developed in both legs, and her weight increased by 5 kg. She attributed the weight gain to increased salt intake. Nine days before the current admission, oral metolazone was added to her diuretic regimen, and the leg edema resolved.
At the time of the current admission, the patient reported nausea and abdominal cramps. She reported no fever, chills, cough, dyspnea, dysuria, flank pain, or vomiting. She had no known sick contacts. Her medical history included hypertension, atrial fibrillation, coronary artery disease, heart failure with reduced ejection fraction, type 2 diabetes mellitus, and obstructive sleep apnea, for which nightly treatment with continuous positive airway pressure had been prescribed. Medications included allopurinol, amiodarone, aspirin, atorvastatin, cyclobenzaprine, enoxaparin, fluticasone, glipizide, loratadine, lorazepam, metformin, metolazone, metoprolol, sertraline, spironolactone, torsemide, warfarin, and zolpidem. The last doses of metolazone, spironolactone, and torsemide were taken more than 24 hours before admission. There were no known drug allergies. Before the recent humeral fracture, the patient had been living alone in an urban area of New England; she required assistance from home health services for bathing and chores and used a walker for ambulation. She did not smoke tobacco or drink alcohol. She had no recent history of travel, and her family history was unremarkable.
On examination, the patient appeared well, without respiratory distress. The temperature was 36.7[degrees]C, the blood pressure 137/63 mm Hg, the heart rate 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. The weight was 126 kg. The oral mucous membranes were dry. The heart sounds were normal, as were the breath sounds throughout both lung fields. There was no edema in the lower legs. The right arm was in a splint.
The blood level of creatinine was 7.66 mg per deciliter (677 [mu]mol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 [mu]mol per liter]), and the level of lactic acid was 7.4 mmol per liter (67 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter [4.5 to 18 mg per deciliter]). Urinalysis by dipstick showed a pH of 5.0 (reference range, 5.0 to 9.0) and a specific gravity of 1.012 (reference range, 1.001 to 1.035), and no protein, blood, nitrites, leukocyte esterase, glucose, or ketones were present. Additional laboratory test results are shown in Table 1.
Chest radiography revealed mild pulmonary interstitial edema. Ultrasonography of the kidneys and urinary tract revealed simple cysts in the left kidney, with no evidence of hydronephrosis or nephrolithiasis.
Intravenous fluids were administered, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of nausea, abdominal cramps, and nonbloody diarrhea, along with her recent stay in a skilled nursing facility, suggest a possible infectious cause. The fact that she was treated with antibiotics (ceftriaxone and doxycycline) a few months prior to her current symptoms further supports this, as antibiotic use can disrupt the normal gut flora and make patients more susceptible to certain infections. The most common infection in this scenario is Clostridium difficile, which often presents with diarrhea and can lead to severe complications including acute kidney failure, which this patient also has. \n\nDiagnosis: Clostridium difficile infection.""
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        ""content"": ""The patient is a 76-year-old woman with a history of heart failure and type 2 diabetes mellitus who presents with nausea, diarrhea, and acute kidney failure. The differential diagnosis for this patient includes acute tubular necrosis (ATN), pre-renal azotemia, post-renal azotemia, and acute interstitial nephritis (AIN). \n\nThe patient's history of heart failure and recent use of diuretics could suggest pre-renal azotemia due to volume depletion. However, the absence of edema in the lower legs and the fact that her weight is close to her dry weight argue against this. \n\nPost-renal azotemia due to obstruction of the urinary tract could also cause acute kidney injury. However, the ultrasonography of the kidneys and urinary tract did not show any evidence of hydronephrosis or nephrolithiasis, making this less likely. \n\nATN could be caused by ischemia or nephrotoxic drugs. The patient's history of heart failure could potentially cause ischemia. However, the patient's medications do not include any known nephrotoxic drugs. \n\nAIN could be caused by an allergic reaction to medications. The patient is on multiple medications, including antibiotics, which could potentially cause AIN. However, the patient does not have any known drug allergies and she has not started any new medications recently. \n\nGiven the patient's history and presentation, the most likely diagnosis is acute tubular necrosis due to ischemia from her heart failure. \n\nDiagnosis: Acute tubular necrosis.""
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}",Acute tubular necrosis,N
10.1056/NEJMcpc2100275,Case 14-2021: A 64-Year-Old Woman with Fever and Pancytopenia,"Hematocrit (%)   26.1 28.9   23.5 23.4
Hemoglobin (g/dl)   8.3 8.6   6.9 6.9
Mean corpuscular volume (fl)   91.9 79.6   83.3 85.1
Mean corpuscular hemoglobin (pg/ml) 27. 1.0 29.2 23.7 26. 4.0 24.5 25.1
Red-cell distribution width (%)   15.9 17.6   21.2 22.0
White-cell count (per μl) 4. .0 4.37 3.97 4.5–11.0 2.56 2.73
Differential count (per μl)
Neutrophils 1.8–7.0 2.11 2.54 1.8–7.7 2.43 2.54
Immature granulocytes 0.0–0.1 0.02 0.02 0.0–0.1 — —
Lymphocytes 1.0–4.8 1.36 1.02 1.0–4.8 0.11 0.69
Eosinophils 0.05–0.25 0.01 0.00   — —
Basophils 0.0–0.3 0.01 0.01 0.0–0.3 — —
Monocytes   0.86 0.47 0.2–1.2 0.02 0.12
Platelet count (per μl) 150,000–
450,000
95,000 186,000 150,000–
450,000
98,000 103,000
Aspartate aminotransferase (U/liter) 15–41 65 45   36 84
Alanine aminotransferase (U/liter) 1 5 71 46   11 49
Alkaline phosphatase (U/liter) 32–100 211 228   209 320
Bilirubin (mg/dl)
Total 0.0–1.2 0.9 0.6  1.3 3.9
Direct 0.0–0.2 0.2 0.2 0.  0.5 2.0
Albumin (g/dl) 3.5–5.2 3.4 3.8   2.9 2.5
Haptoglobin (mg/dl) 3 00 38 <14   <14 —
Direct Coombs’ test
IgG Negative — Negative — — —
IgA Negative — — — — —
IgM Negative — — — — —
C3 Negative — Negative — — —
C3c Negative — — — — —
C3d Negative — — — — —
Reticulocytes (%) 0.8–1.8 4.6 3.5 0.7–2.5 3.1 —
Lactate dehydrogenase (U/liter) 98–192 — 513 11 10 699 721
Ferritin (μg/liter) 13–150 — 1248 2 00 3402 —
d-Dimer (ng/ml) — — —   1865 —
Fibrinogen (mg/dl) — — — 15 0 662 428
C-reactive protein (mg/liter) — — —  .0 144.7 50.8
Erythrocyte sedimentation rate (mm/hr)  0 — 32  0 60 36
Triglycerides (mg/dl)  0 194 —   269 —
Soluble interleukin-2 receptor (pg/ml) — — — 532–1891 18,261 —                           Bilirubin Negative Negative — Negative Negative —
Urobilinogen Negative 2+ — Negative 4+ —
Blood Negative Negative — Negative Negative —
Glucose Negative Negative — Negative Negative —
Ketones Negative Negative — Negative Negative —
Leukocyte esterase Negative 1+ — Negative 1+ —
Nitrites Negative Negative — Negative Negative —
pH 5. .0 5.0 —   6.5 —
Specific gravity 1.003–1.030 1.018 —   1.019 —
Protein Negative Negative — Negative Negative —",Babesiosis.,Babesiosis possibly complicated by hemophagocytic lymphohistiocytosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old woman was admitted to this hospital in early winter with fever and pancytopenia.
The patient, who had multiple sclerosis, had been in her usual state of health until 7 months before admission, when nausea and fatigue developed. Over the next 2 months, these symptoms worsened, and in the context of severe nausea, two episodes of vasovagal syncope occurred. During an evaluation for syncope, anemia was noted. Five months before admission, the patient was evaluated by her primary care provider at another hospital. The weight was 87.6 kg, and the results of physical examination were normal. Blood levels of electrolytes, glucose, cobalamin, folate, iron, iron saturation, and total iron-binding capacity were normal, as were the results of kidney-function tests; other laboratory test results are shown in Table 1. Iron supplementation was prescribed.	
Table 1
Nausea and fatigue persisted. Three months before admission, the patient was again evaluated by her primary care provider at the other hospital. The weight was 84.4 kg; the remainder of the examination was unchanged. Blood levels of electrolytes and glucose were normal, as were the results of kidney-function tests; other laboratory test results are shown in Table 1. Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed cholelithiasis and splenomegaly, with the spleen measuring 17 cm in the craniocaudal dimension (normal value, <=12 cm).
Two and a half months before admission, the patient was evaluated in a hematology clinic affiliated with the other hospital. She reported persistent nausea and fatigue, poor appetite with reduced oral intake, and 2 weeks of dyspnea on exertion. There was no orthopnea or paroxysmal nocturnal dyspnea. The weight was 83.2 kg, and the spleen tip was palpable four fingerbreadths below the costal margin; the remainder of the physical examination was normal. A bone marrow biopsy was performed, and examination of the bone marrow specimen revealed mildly hypercellular marrow with maturing trilineage hematopoiesis and mild dyserythropoiesis.
Treatment with prednisone and folic acid was begun. Ocrelizumab infusions for multiple sclerosis were stopped. Nausea and fatigue persisted, and fevers and sweats developed. After 3 weeks of treatment with prednisone, the anemia had not abated and the patient had temperatures as high as 39.0[degrees]C. Testing for influenza A and B viruses was negative. Two units of packed red cells were transfused. The course of prednisone was tapered off over the next 18 days, and the patient was referred to a hematologist affiliated with this hospital.
In the hematology clinic, the patient reported that the fevers had resolved but the fatigue, weakness, and poor appetite had worsened. She felt too fatigued to walk, and she had recently had a fall without loss of consciousness. The weight was 82.4 kg; splenomegaly was present, and the remainder of the examination was unchanged. The patient was admitted to this hospital for further evaluation and treatment.
In addition to relapsing-remitting multiple sclerosis, there was a history of trigeminal neuralgia, restless legs syndrome, vasovagal syncope when blood samples were obtained, and an elevated alkaline phosphatase level for 1 year without a clear cause. Medications included oxcarbazepine, gabapentin, ropinirole, folic acid, and cholecalciferol. There were no known drug allergies. The patient had quit smoking 20 years earlier and did not drink alcohol or use illicit drugs. She lived in a suburban area of New England with her adult son and pet cat and dog. Her backyard adjoined a large wooded area where deer were often seen. She worked in health care administration. Her family history included diabetes in her mother, lung cancer in her father, and multiple sclerosis in her sister.
On examination, the patient appeared pale but not unwell. The temperature was 38.3[degrees]C, the blood pressure 90/54 mm Hg, the heart rate 93 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 93% while she was breathing ambient air. The weight was 79.8 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 32.2. The conjunctivae were pale. The heart rate was regular, with normal first and second heart sounds (S1 and S2) and a soft systolic murmur. There was edema in the legs. The remainder of the examination was normal. Blood levels of homocysteine, methylmalonic acid, arsenic, cadmium, lead, and mercury were normal, as were the results of serum protein electrophoresis and coagulation tests; other laboratory test results are shown in Table 1. Blood cultures were obtained. Two units of packed red cells were transfused, and one dose of intravenous furosemide was administered. Intravenous methylprednisolone was administered daily for 3 days, and the patient reported a decrease in weakness and fatigue.
Dr. Dexter P. Mendoza: On hospital day 4, CT of the chest, abdomen, and pelvis (Figure 1A) revealed splenomegaly, with the spleen measuring 19 cm in the craniocaudal dimension. Concurrent positron-emission tomography with injection of 18F-fluorodeoxyglucose (Figure 1B) revealed intense uptake in the spleen and diffuse uptake in the bone marrow throughout the axial and appendicular skeleton.	
Figure 1 
Dr. Miller: On hospital day 5, the patient reported a recurrence of severe fatigue and generalized weakness. The temperature was 39.0[degrees]C and the heart rate 130 beats per minute. The results of physical examination were otherwise unchanged. Laboratory test results are shown in Table 1.
A diagnostic test result was received
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old woman was admitted to this hospital in early winter with fever and pancytopenia.
The patient, who had multiple sclerosis, had been in her usual state of health until 7 months before admission, when nausea and fatigue developed. Over the next 2 months, these symptoms worsened, and in the context of severe nausea, two episodes of vasovagal syncope occurred. During an evaluation for syncope, anemia was noted. Five months before admission, the patient was evaluated by her primary care provider at another hospital. The weight was 87.6 kg, and the results of physical examination were normal. Blood levels of electrolytes, glucose, cobalamin, folate, iron, iron saturation, and total iron-binding capacity were normal, as were the results of kidney-function tests; other laboratory test results are shown in Table 1. Iron supplementation was prescribed.	
Table 1
Nausea and fatigue persisted. Three months before admission, the patient was again evaluated by her primary care provider at the other hospital. The weight was 84.4 kg; the remainder of the examination was unchanged. Blood levels of electrolytes and glucose were normal, as were the results of kidney-function tests; other laboratory test results are shown in Table 1. Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed cholelithiasis and splenomegaly, with the spleen measuring 17 cm in the craniocaudal dimension (normal value, <=12 cm).
Two and a half months before admission, the patient was evaluated in a hematology clinic affiliated with the other hospital. She reported persistent nausea and fatigue, poor appetite with reduced oral intake, and 2 weeks of dyspnea on exertion. There was no orthopnea or paroxysmal nocturnal dyspnea. The weight was 83.2 kg, and the spleen tip was palpable four fingerbreadths below the costal margin; the remainder of the physical examination was normal. A bone marrow biopsy was performed, and examination of the bone marrow specimen revealed mildly hypercellular marrow with maturing trilineage hematopoiesis and mild dyserythropoiesis.
Treatment with prednisone and folic acid was begun. Ocrelizumab infusions for multiple sclerosis were stopped. Nausea and fatigue persisted, and fevers and sweats developed. After 3 weeks of treatment with prednisone, the anemia had not abated and the patient had temperatures as high as 39.0[degrees]C. Testing for influenza A and B viruses was negative. Two units of packed red cells were transfused. The course of prednisone was tapered off over the next 18 days, and the patient was referred to a hematologist affiliated with this hospital.
In the hematology clinic, the patient reported that the fevers had resolved but the fatigue, weakness, and poor appetite had worsened. She felt too fatigued to walk, and she had recently had a fall without loss of consciousness. The weight was 82.4 kg; splenomegaly was present, and the remainder of the examination was unchanged. The patient was admitted to this hospital for further evaluation and treatment.
In addition to relapsing-remitting multiple sclerosis, there was a history of trigeminal neuralgia, restless legs syndrome, vasovagal syncope when blood samples were obtained, and an elevated alkaline phosphatase level for 1 year without a clear cause. Medications included oxcarbazepine, gabapentin, ropinirole, folic acid, and cholecalciferol. There were no known drug allergies. The patient had quit smoking 20 years earlier and did not drink alcohol or use illicit drugs. She lived in a suburban area of New England with her adult son and pet cat and dog. Her backyard adjoined a large wooded area where deer were often seen. She worked in health care administration. Her family history included diabetes in her mother, lung cancer in her father, and multiple sclerosis in her sister.
On examination, the patient appeared pale but not unwell. The temperature was 38.3[degrees]C, the blood pressure 90/54 mm Hg, the heart rate 93 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 93% while she was breathing ambient air. The weight was 79.8 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 32.2. The conjunctivae were pale. The heart rate was regular, with normal first and second heart sounds (S1 and S2) and a soft systolic murmur. There was edema in the legs. The remainder of the examination was normal. Blood levels of homocysteine, methylmalonic acid, arsenic, cadmium, lead, and mercury were normal, as were the results of serum protein electrophoresis and coagulation tests; other laboratory test results are shown in Table 1. Blood cultures were obtained. Two units of packed red cells were transfused, and one dose of intravenous furosemide was administered. Intravenous methylprednisolone was administered daily for 3 days, and the patient reported a decrease in weakness and fatigue.
Dr. Dexter P. Mendoza: On hospital day 4, CT of the chest, abdomen, and pelvis (Figure 1A) revealed splenomegaly, with the spleen measuring 19 cm in the craniocaudal dimension. Concurrent positron-emission tomography with injection of 18F-fluorodeoxyglucose (Figure 1B) revealed intense uptake in the spleen and diffuse uptake in the bone marrow throughout the axial and appendicular skeleton.	
Figure 1 
Dr. Miller: On hospital day 5, the patient reported a recurrence of severe fatigue and generalized weakness. The temperature was 39.0[degrees]C and the heart rate 130 beats per minute. The results of physical examination were otherwise unchanged. Laboratory test results are shown in Table 1.
A diagnostic test result was received
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fever, pancytopenia, and splenomegaly, along with her history of exposure to wooded areas where deer are often seen, suggest a tick-borne illness. The patient's condition did not improve with prednisone treatment, which would be expected if the cause was autoimmune. The patient's symptoms and the timing of their onset (in early winter) are consistent with tick-borne diseases, which can present months after the initial tick bite. The patient's severe fatigue and generalized weakness, which recurred after a brief improvement with methylprednisolone, also suggest an ongoing infectious process rather than an autoimmune condition. Therefore, the most likely diagnosis is a tick-borne illness such as babesiosis or anaplasmosis.\n\nDiagnosis: Tick-borne illness (Babesiosis or Anaplasmosis)""
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        ""content"": ""The patient's symptoms of fever, pancytopenia, and splenomegaly, along with her history of exposure to wooded areas where deer are often seen, suggest a tick-borne illness. The patient's condition did not improve with prednisone treatment, which would be expected if the cause was autoimmune. The patient's symptoms and the timing of their onset (in early winter) are consistent with tick-borne diseases, which can cause a range of nonspecific symptoms that often include fever and fatigue. The patient's location in New England also increases the likelihood of a tick-borne disease, as several such diseases are known to be endemic in that region. \n\nDiagnosis: Tick-borne illness, possibly babesiosis or anaplasmosis.""
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        ""content"": ""The patient is a 64-year-old woman with a history of multiple sclerosis who presents with fever, pancytopenia, nausea, fatigue, and splenomegaly. The differential diagnosis for this patient includes autoimmune disease, malignancy, infection, and drug-induced pancytopenia. The patient's history of multiple sclerosis raises the possibility of an autoimmune process. However, the patient's symptoms have not improved with prednisone, making this less likely. The patient's splenomegaly and pancytopenia could be indicative of a hematologic malignancy such as leukemia or lymphoma. However, a bone marrow biopsy showed only mildly hypercellular marrow with maturing trilineage hematopoiesis and mild dyserythropoiesis, which does not support a diagnosis of malignancy. The patient's fever and pancytopenia could also be due to an infection. Given the patient's exposure to deer and her pet cat and dog, tick-borne diseases such as Lyme disease or anaplasmosis, or cat-scratch disease could be considered. However, these diseases would not typically cause splenomegaly. Finally, the patient's pancytopenia could be drug-induced. However, the patient's medications do not typically cause pancytopenia. Given the patient's symptoms, exposure history, and the lack of a clear alternative diagnosis, a tick-borne disease seems most likely.\n\nDiagnosis: Tick-borne disease, such as anaplasmosis or babesiosis.""
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10.1056/NEJMcpc2100277,Case 13-2021: A Newborn Girl with a Neck Mass,"White-cell count (per μl) 900 0,000 17,530
Differential count (per μl)
Neutrophils 590 6,100 12,620
Lymphocytes 200 ,100 3860
Monocytes 40 300 700
Hemoglobin (g/dl) 9. .5‡ 10.0
Hematocrit (%) 42.0–60.0 29.5
Platelet count (per μl)   229,000
Glucose (mg/dl) 60–100 80
Lactate dehydrogenase (U/liter) 11 10 319
Thyrotropin (μU/ml) 0.4 0 3.82
Free thyroxine (ng/dl) 0.9–1.8 1.8
Alpha-fetoprotein (ng/ml) <7.9 107,048.0
Beta human chorionic gonadotropin 
(IU/ml)
<50.0 7.3
Urine
Homovanillic acid (mg/g of creatinine) <35.0 8.8
Vanillylmandelic acid (mg/g of creati‚Äë
nine)
<25.0       4.5",Nodular follicular thyroid neoplasm with a somatic NRAS mutation.,"Congenital neck mass most likely of sympathetic chain origin, most consistent with neuroblastoma.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A newborn girl was admitted to the neonatal intensive care unit of this hospital after a planned delivery by cesarean section because of a neck mass.
During pregnancy, the patient's mother was 41 years old (gravida 3, para 1) and received prenatal care at another hospital. At 7 weeks of gestation, vaginal bleeding occurred because of a subchorionic hematoma. At 10 weeks of gestation, the mother's blood thyrotropin level was 0.01 [mu]U per milliliter (reference range, 0.40 to 5.00); levels of free thyroxine (free T4) and total triiodothyronine (total T3) were not obtained. At 19 weeks of gestation, the thyrotropin level was 0.44 [mu]U per milliliter and an ultrasonographic survey of the fetal anatomy was normal. During the third trimester, gestational diabetes was diagnosed; glycemic control was maintained with dietary changes.
Four weeks before delivery, at 34 weeks 6 days of gestation, a routine transvaginal ultrasonographic survey of fetal growth revealed a new mass on the right side of the fetus's neck that measured 2.6 cm by 3.4 cm by 3.0 cm. The mother was referred to the obstetrics clinic of this hospital for further evaluation and treatment.
Dr. Randheer Shailam: At 35 weeks 6 days of gestation, obstetrical ultrasonography performed at this hospital (Figure 1A) confirmed the presence of a 4.6-cm mass on the right side of the neck. The mass was hyperechoic and well circumscribed and had internal vascularity; the remainder of the survey of fetal anatomy was normal. Magnetic resonance imaging (MRI) of the fetus, performed without the intravenous administration of contrast material (Figure 1B, 1C, and 1D), revealed displacement of the trachea without compression.	
Figure 1
Dr. Sparger: For multiple weeks, the fetal biophysical profile score was 8 out of 8, indicating normal breathing motion, movement, tone, and amniotic fluid volume. The mother met with providers from Maternal-Fetal Medicine, Pediatric Surgery, Pediatric Otolaryngology, and Neonatology to discuss the plan for delivery and neonatal airway management at birth, including the possibility of an ex utero intrapartum treatment (EXIT) procedure. The mother initially had a preference for a vaginal delivery, given her history of a successful vaginal delivery with a previous pregnancy. However, after conversations with Maternal-Fetal Medicine providers, the decision was made to proceed with a scheduled cesarean section at 39 weeks of gestation to minimize the risks of labor dystocia and asynclitism due to fetal neck position and any associated birth trauma, as well as to allow for controlled timing of the delivery with multidisciplinary team members present.
The mother had a history of anxiety, post-traumatic stress disorder, and known mutations in both copies of the gene encoding methylenetetrahydrofolate reductase (MTHFR). Eleven years earlier, her first pregnancy had ended at full term with a vaginal delivery. Three years earlier, her second pregnancy had ended at 13 weeks of gestation with elective termination because of the diagnosis of pentalogy of Cantrell (a syndrome of midline abdominal and chest wall defects, including ectopia cordis and omphalocele). During her current pregnancy, she had taken prenatal vitamins, cholecalciferol, and pyridoxine, as well as lorazepam as needed for anxiety. Prenatal screening tests were negative for gonorrhea, chlamydia, syphilis, human immunodeficiency virus, and hepatitis B; equivocal for immunity to rubella; and positive for group B streptococcal colonization.
The patient (baby) had a healthy father and sister. Her family history included hypothyroidism in her maternal grandmother, sleep apnea in her paternal grandfather, and diabetes in her paternal grandmother. In addition, her maternal aunt had thyrotoxicosis, a paternal uncle had diabetes, and another paternal uncle had blindness, deafness, and cognitive developmental delay.
At 39 weeks of gestation, the baby was delivered by cesarean section. The birth weight was 3060 g (35th percentile), the length 48 cm (26th percentile), and the head circumference 34.5 cm (60th percentile). She had a spontaneous cry, decreased tone, and spontaneous respirations. There was a large firm mass on the right side of the neck. The 1-minute Apgar score was 6.
At 3 minutes of life, increased work of breathing developed; treatment with continuous positive airway pressure of 5 cm of water was administered. At 5 minutes of life, the Apgar score was 7 but the increased work of breathing worsened, with nasal flaring, grunting, and subcostal retractions; the fraction of inspired oxygen (FIO2) was increased to 100%. At 10 minutes of life, the Apgar score was 8. Direct laryngoscopy revealed deviation of the trachea, larynx, subglottis, and right piriform sinus. Tracheal intubation was performed with rigid bronchoscopy; because of clinically significant airway obstruction, tracheostomy was performed.
At 8 hours of life, the blood hemoglobin level was 10.0 g per deciliter (reference range for neonates, 13.5 to 19.5), the thyrotropin level 3.82 [mu]U per milliliter, the alpha-fetoprotein level 107,048.0 ng per milliliter (reference range, <7.9), and the beta human chorionic gonadotropin (hCG) level 7.3 IU per milliliter (reference range, <50.0). Other laboratory test results are shown in Table 1.	
Table 1
Dr. Shailam: On ultrasonography of the head and neck (Figure 2A), the mass on the right side of the neck measured 3.7 cm by 3.8 cm by 3.1 cm and was markedly hypervascular, with lateral displacement of the internal jugular vein and carotid artery. On MRI and magnetic resonance angiography of the neck, performed with and without the intravenous administration of contrast material (Figure 2B and 2C), the mass appeared to arise from the sympathetic chain.	
Figure 2 
Dr. Sparger: During the first week of life, the vital signs remained normal, except for intermittent oxygen desaturation events while the patient was breathing through a humidified tracheostomy mask (FIO2, 21%); these desaturations resolved rapidly without intervention. The weight increased along the 30th percentile.
A diagnostic procedure was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A newborn girl was admitted to the neonatal intensive care unit of this hospital after a planned delivery by cesarean section because of a neck mass.
During pregnancy, the patient's mother was 41 years old (gravida 3, para 1) and received prenatal care at another hospital. At 7 weeks of gestation, vaginal bleeding occurred because of a subchorionic hematoma. At 10 weeks of gestation, the mother's blood thyrotropin level was 0.01 [mu]U per milliliter (reference range, 0.40 to 5.00); levels of free thyroxine (free T4) and total triiodothyronine (total T3) were not obtained. At 19 weeks of gestation, the thyrotropin level was 0.44 [mu]U per milliliter and an ultrasonographic survey of the fetal anatomy was normal. During the third trimester, gestational diabetes was diagnosed; glycemic control was maintained with dietary changes.
Four weeks before delivery, at 34 weeks 6 days of gestation, a routine transvaginal ultrasonographic survey of fetal growth revealed a new mass on the right side of the fetus's neck that measured 2.6 cm by 3.4 cm by 3.0 cm. The mother was referred to the obstetrics clinic of this hospital for further evaluation and treatment.
Dr. Randheer Shailam: At 35 weeks 6 days of gestation, obstetrical ultrasonography performed at this hospital (Figure 1A) confirmed the presence of a 4.6-cm mass on the right side of the neck. The mass was hyperechoic and well circumscribed and had internal vascularity; the remainder of the survey of fetal anatomy was normal. Magnetic resonance imaging (MRI) of the fetus, performed without the intravenous administration of contrast material (Figure 1B, 1C, and 1D), revealed displacement of the trachea without compression.	
Figure 1
Dr. Sparger: For multiple weeks, the fetal biophysical profile score was 8 out of 8, indicating normal breathing motion, movement, tone, and amniotic fluid volume. The mother met with providers from Maternal-Fetal Medicine, Pediatric Surgery, Pediatric Otolaryngology, and Neonatology to discuss the plan for delivery and neonatal airway management at birth, including the possibility of an ex utero intrapartum treatment (EXIT) procedure. The mother initially had a preference for a vaginal delivery, given her history of a successful vaginal delivery with a previous pregnancy. However, after conversations with Maternal-Fetal Medicine providers, the decision was made to proceed with a scheduled cesarean section at 39 weeks of gestation to minimize the risks of labor dystocia and asynclitism due to fetal neck position and any associated birth trauma, as well as to allow for controlled timing of the delivery with multidisciplinary team members present.
The mother had a history of anxiety, post-traumatic stress disorder, and known mutations in both copies of the gene encoding methylenetetrahydrofolate reductase (MTHFR). Eleven years earlier, her first pregnancy had ended at full term with a vaginal delivery. Three years earlier, her second pregnancy had ended at 13 weeks of gestation with elective termination because of the diagnosis of pentalogy of Cantrell (a syndrome of midline abdominal and chest wall defects, including ectopia cordis and omphalocele). During her current pregnancy, she had taken prenatal vitamins, cholecalciferol, and pyridoxine, as well as lorazepam as needed for anxiety. Prenatal screening tests were negative for gonorrhea, chlamydia, syphilis, human immunodeficiency virus, and hepatitis B; equivocal for immunity to rubella; and positive for group B streptococcal colonization.
The patient (baby) had a healthy father and sister. Her family history included hypothyroidism in her maternal grandmother, sleep apnea in her paternal grandfather, and diabetes in her paternal grandmother. In addition, her maternal aunt had thyrotoxicosis, a paternal uncle had diabetes, and another paternal uncle had blindness, deafness, and cognitive developmental delay.
At 39 weeks of gestation, the baby was delivered by cesarean section. The birth weight was 3060 g (35th percentile), the length 48 cm (26th percentile), and the head circumference 34.5 cm (60th percentile). She had a spontaneous cry, decreased tone, and spontaneous respirations. There was a large firm mass on the right side of the neck. The 1-minute Apgar score was 6.
At 3 minutes of life, increased work of breathing developed; treatment with continuous positive airway pressure of 5 cm of water was administered. At 5 minutes of life, the Apgar score was 7 but the increased work of breathing worsened, with nasal flaring, grunting, and subcostal retractions; the fraction of inspired oxygen (FIO2) was increased to 100%. At 10 minutes of life, the Apgar score was 8. Direct laryngoscopy revealed deviation of the trachea, larynx, subglottis, and right piriform sinus. Tracheal intubation was performed with rigid bronchoscopy; because of clinically significant airway obstruction, tracheostomy was performed.
At 8 hours of life, the blood hemoglobin level was 10.0 g per deciliter (reference range for neonates, 13.5 to 19.5), the thyrotropin level 3.82 [mu]U per milliliter, the alpha-fetoprotein level 107,048.0 ng per milliliter (reference range, <7.9), and the beta human chorionic gonadotropin (hCG) level 7.3 IU per milliliter (reference range, <50.0). Other laboratory test results are shown in Table 1.	
Table 1
Dr. Shailam: On ultrasonography of the head and neck (Figure 2A), the mass on the right side of the neck measured 3.7 cm by 3.8 cm by 3.1 cm and was markedly hypervascular, with lateral displacement of the internal jugular vein and carotid artery. On MRI and magnetic resonance angiography of the neck, performed with and without the intravenous administration of contrast material (Figure 2B and 2C), the mass appeared to arise from the sympathetic chain.	
Figure 2 
Dr. Sparger: During the first week of life, the vital signs remained normal, except for intermittent oxygen desaturation events while the patient was breathing through a humidified tracheostomy mask (FIO2, 21%); these desaturations resolved rapidly without intervention. The weight increased along the 30th percentile.
A diagnostic procedure was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a newborn with a neck mass detected prenatally. The mass is described as hyperechoic and well circumscribed with internal vascularity on ultrasound, and appears to arise from the sympathetic chain on MRI. These findings are consistent with a neuroblastoma, a common extracranial solid tumor in infants that often arises from the adrenal gland or sympathetic ganglia. The elevated alpha-fetoprotein level is not typical for neuroblastoma, but it can be elevated in newborns and gradually decrease over the first year of life. \n\nNeuroblastoma""
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        ""content"": ""The newborn girl presents with a neck mass that was detected prenatally. The mass is hyperechoic, well circumscribed, and has internal vascularity. It displaces the trachea without compression. The differential diagnosis for a neck mass in a newborn includes congenital anomalies such as branchial cleft cyst, thyroglossal duct cyst, and vascular malformations, as well as neoplasms such as neuroblastoma, teratoma, and lymphangioma. Branchial cleft cysts and thyroglossal duct cysts are typically midline and do not have internal vascularity, making these less likely. Vascular malformations can be ruled out as they would not cause displacement of the trachea. Teratomas are typically heterogeneous with areas of calcification, fat, and fluid, which is not consistent with the imaging findings in this case. Lymphangiomas are typically multiloculated cystic masses, which is also not consistent with the imaging findings. Neuroblastoma, a tumor that arises from the sympathetic chain, is consistent with the imaging findings and the displacement of the trachea. Furthermore, the patient's elevated alpha-fetoprotein level is consistent with a diagnosis of neuroblastoma.\n\nDiagnosis: Neuroblastoma.""
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10.1056/NEJMcpc2100276,Case 12-2021: A 78-Year-Old Man with a Rash on the Scalp and Face,"White-cell count (per μl) 400 ,000 8190
Differential count (per μl)
Neutrophils 1800–7000 6070
Lymphocytes   900
Monocytes   1060
Eosinophils 5 50 80
Hemoglobin (g/dl)   12.5
Hematocrit (%)   36.5
Platelet count (per μl)   124,000
Sodium (mmol/liter)   125
Potassium (mmol/liter)   4.8
Chloride (mmol/liter)   89
Carbon dioxide (mmol/liter)   24
Urea nitrogen (mg/dl)   21
Creatinine (mg/dl)   0.99
Glucose (mg/dl)   122
Erythrocyte sedimentation rate (mm/hr)   5
C-reactive protein (mg/liter)  .0 18.8
Lactic acid (mmol/liter)   1.1",Varicella–zoster virus infection,Varicella–zoster virus infection,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 78-year-old man was admitted to this hospital because of a rash on the forehead and frontal scalp and edema of the left eyelids.
The patient had been well until 3 days before presentation, when pressurelike pain developed in the left side of the forehead and frontal scalp and the bilateral maxillary sinuses and upper jaws. He described the pain as similar to previous episodes of sinusitis. He was evaluated in the primary care clinic of another hospital, and treatment with oral clindamycin was started for a presumed diagnosis of sinusitis.
Two days before presentation, the patient noted erythema and small reddish-brown skin lesions on the left side of the forehead and frontal scalp. His barber had pointed out a similar spot on the top of his scalp 2 weeks earlier. The skin lesions were not painful or itchy, and he did not seek medical evaluation.
On the day of presentation, the patient awoke from sleep and noted redness and swelling of the left eyelids. The skin lesions on the left side of the forehead and frontal scalp had increased in number, and some were covered with hemorrhagic crust. There was pain with movement of the left eye and blurry vision. Over the course of several hours, the swelling of the left eyelids worsened and the patient was unable to fully open the left eye. He presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported no ocular or nasal discharge, no changes in taste or hearing, and no jaw claudication. He had not recently changed his shampoo or been in a pool or hot tub. He had a history of recurrent sinus infection, allergic rhinitis, depression, benign prostatic hyperplasia, hypogonadism, and restless legs syndrome. He had received a diagnosis of rectal cancer 15 years earlier, which had led to partial colectomy, as well as a diagnosis of testicular cancer 50 years earlier, which had led to orchiectomy and radiation therapy. His ocular history included bilateral mild ptosis; he had undergone bilateral cataract extraction with intraocular lens implantation. Medications included finasteride, tamsulosin, carbidopa-levodopa, nasal azelastine and fluticasone, and topical testosterone. Levofloxacin, cefaclor, and sulfamethoxazole-trimethoprim had caused a rash. The patient was a retired engineer and lived with his wife in a coastal community of New England. He had previously smoked a pipe but had quit 30 years earlier. He drank a quarter glass of wine daily. His family history included skin cancer in his maternal grandmother and macular degeneration in his sister.
On examination, the temperature was 38.1[degrees]C, the blood pressure 122/58 mm Hg, and the heart rate 74 beats per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 31.9. Visual acuity without glasses was 20/40 in the right eye and 20/50 in the left eye. Results of Ishihara color testing were normal. The pupils were equal, round, and reactive to light; there was no relative afferent pupillary defect. Extraocular movements were full. There was complete ptosis of the left upper eyelid, along with erythema and edema of left upper and lower lids. There was mild ptosis of the right upper lid. There was no proptosis. The intraocular pressure was 17 mm Hg in both eyes. Slit-lamp examination revealed diffuse conjunctival injection and inferior chemosis in the left eye. The corneas were clear, and no cells were visualized in the anterior chambers. Results of dilated fundoscopic examination were normal. There was prominent erythema affecting the forehead, left side of the anterior scalp, and left eyelids. Multiple coalescing erosions covered with hemorrhagic and serous crust were seen at sites of erythema, mainly affecting the left side of the forehead and extending to the midline, the frontal scalp, and the left upper eyelid. Erosions and erythema affected the right side of the forehead, as well, but to a much lesser extent. The remainder of the physical examination was normal.
Laboratory evaluation revealed a blood sodium level of 125 mmol per liter (reference range, 135 to 145). Results of kidney- and liver-function tests were normal. Tests for human immunodeficiency virus types 1 and 2 were negative. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Hillary R. Kelly: Computed tomography (CT) of the head and face (Figure 1), performed after the administration of intravenous contrast material, revealed marked swelling affecting the soft tissue over the left orbit and frontal sinus and extending superiorly along the superficial soft tissue of the frontal scalp, predominantly on the left side. The globe, orbit, and retrobulbar soft tissue were normal. The right maxillary sinus showed nearly complete opacification with wall thickening and sclerosis, findings consistent with chronic inflammation and sinusitis. There was a defect in the medial wall of the right maxillary sinus that was consistent with previous sinus surgery. The other paranasal sinuses, including the left maxillary sinus, ethmoid sinuses, and sphenoid sinuses, were well aerated.	
Figure 1 
Dr. Chiou: Empirical treatment with valacyclovir, amoxicillin-clavulanate, and topical bacitracin-polymyxin B was started. The next day, the edema and erythema of the left eyelids worsened, and there was new edema and erythema of the right eyelids. The patient was unable to open his eyes. He began to have visual hallucinations, and his wife noted that he was confused. The skin lesions on the left side of the forehead were unchanged, and new round punched-out erosions with overlying hemorrhagic crust were present on the right side of the forehead (Figure 2). Empirical treatment with intravenous vancomycin, cefepime, and acyclovir was started.	
Figure 2 
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 78-year-old man was admitted to this hospital because of a rash on the forehead and frontal scalp and edema of the left eyelids.
The patient had been well until 3 days before presentation, when pressurelike pain developed in the left side of the forehead and frontal scalp and the bilateral maxillary sinuses and upper jaws. He described the pain as similar to previous episodes of sinusitis. He was evaluated in the primary care clinic of another hospital, and treatment with oral clindamycin was started for a presumed diagnosis of sinusitis.
Two days before presentation, the patient noted erythema and small reddish-brown skin lesions on the left side of the forehead and frontal scalp. His barber had pointed out a similar spot on the top of his scalp 2 weeks earlier. The skin lesions were not painful or itchy, and he did not seek medical evaluation.
On the day of presentation, the patient awoke from sleep and noted redness and swelling of the left eyelids. The skin lesions on the left side of the forehead and frontal scalp had increased in number, and some were covered with hemorrhagic crust. There was pain with movement of the left eye and blurry vision. Over the course of several hours, the swelling of the left eyelids worsened and the patient was unable to fully open the left eye. He presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported no ocular or nasal discharge, no changes in taste or hearing, and no jaw claudication. He had not recently changed his shampoo or been in a pool or hot tub. He had a history of recurrent sinus infection, allergic rhinitis, depression, benign prostatic hyperplasia, hypogonadism, and restless legs syndrome. He had received a diagnosis of rectal cancer 15 years earlier, which had led to partial colectomy, as well as a diagnosis of testicular cancer 50 years earlier, which had led to orchiectomy and radiation therapy. His ocular history included bilateral mild ptosis; he had undergone bilateral cataract extraction with intraocular lens implantation. Medications included finasteride, tamsulosin, carbidopa-levodopa, nasal azelastine and fluticasone, and topical testosterone. Levofloxacin, cefaclor, and sulfamethoxazole-trimethoprim had caused a rash. The patient was a retired engineer and lived with his wife in a coastal community of New England. He had previously smoked a pipe but had quit 30 years earlier. He drank a quarter glass of wine daily. His family history included skin cancer in his maternal grandmother and macular degeneration in his sister.
On examination, the temperature was 38.1[degrees]C, the blood pressure 122/58 mm Hg, and the heart rate 74 beats per minute. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 31.9. Visual acuity without glasses was 20/40 in the right eye and 20/50 in the left eye. Results of Ishihara color testing were normal. The pupils were equal, round, and reactive to light; there was no relative afferent pupillary defect. Extraocular movements were full. There was complete ptosis of the left upper eyelid, along with erythema and edema of left upper and lower lids. There was mild ptosis of the right upper lid. There was no proptosis. The intraocular pressure was 17 mm Hg in both eyes. Slit-lamp examination revealed diffuse conjunctival injection and inferior chemosis in the left eye. The corneas were clear, and no cells were visualized in the anterior chambers. Results of dilated fundoscopic examination were normal. There was prominent erythema affecting the forehead, left side of the anterior scalp, and left eyelids. Multiple coalescing erosions covered with hemorrhagic and serous crust were seen at sites of erythema, mainly affecting the left side of the forehead and extending to the midline, the frontal scalp, and the left upper eyelid. Erosions and erythema affected the right side of the forehead, as well, but to a much lesser extent. The remainder of the physical examination was normal.
Laboratory evaluation revealed a blood sodium level of 125 mmol per liter (reference range, 135 to 145). Results of kidney- and liver-function tests were normal. Tests for human immunodeficiency virus types 1 and 2 were negative. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Hillary R. Kelly: Computed tomography (CT) of the head and face (Figure 1), performed after the administration of intravenous contrast material, revealed marked swelling affecting the soft tissue over the left orbit and frontal sinus and extending superiorly along the superficial soft tissue of the frontal scalp, predominantly on the left side. The globe, orbit, and retrobulbar soft tissue were normal. The right maxillary sinus showed nearly complete opacification with wall thickening and sclerosis, findings consistent with chronic inflammation and sinusitis. There was a defect in the medial wall of the right maxillary sinus that was consistent with previous sinus surgery. The other paranasal sinuses, including the left maxillary sinus, ethmoid sinuses, and sphenoid sinuses, were well aerated.	
Figure 1 
Dr. Chiou: Empirical treatment with valacyclovir, amoxicillin-clavulanate, and topical bacitracin-polymyxin B was started. The next day, the edema and erythema of the left eyelids worsened, and there was new edema and erythema of the right eyelids. The patient was unable to open his eyes. He began to have visual hallucinations, and his wife noted that he was confused. The skin lesions on the left side of the forehead were unchanged, and new round punched-out erosions with overlying hemorrhagic crust were present on the right side of the forehead (Figure 2). Empirical treatment with intravenous vancomycin, cefepime, and acyclovir was started.	
Figure 2 
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Herpes Zoster Ophthalmicus. The patient's symptoms of a rash on the forehead and scalp, along with edema of the eyelids, are consistent with this condition. Herpes Zoster Ophthalmicus is a reactivation of the varicella-zoster virus in the ophthalmic division of the trigeminal nerve, which can cause a rash in the distribution of the nerve along with ocular symptoms. The patient's history of pain in the forehead and scalp prior to the appearance of the rash, as well as the distribution of the rash, are also consistent with this diagnosis. The worsening of symptoms despite treatment for bacterial infection further supports a viral cause.""
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        ""content"": ""Herpes Zoster Ophthalmicus. The patient's symptoms of a rash on the forehead and scalp, along with edema of the eyelids, are consistent with this condition. Herpes Zoster Ophthalmicus is a reactivation of the varicella-zoster virus in the ophthalmic division of the trigeminal nerve, which can cause a rash in the distribution of the nerve along with ocular symptoms. The patient's history of pain in the area prior to the appearance of the rash, as well as the progression of the rash and ocular symptoms, support this diagnosis. The hallucinations and confusion could be due to encephalitis, a potential complication of herpes zoster.""
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        ""content"": ""The patient is a 78-year-old man presenting with a rash on the forehead and frontal scalp, edema of the left eyelids, and pressure-like pain in the left side of the forehead and frontal scalp. The differential diagnosis for this patient includes bacterial skin infection (cellulitis), herpes zoster (shingles), and a fungal infection. The patient's history of recurrent sinus infection and recent treatment with oral clindamycin for presumed sinusitis could suggest a bacterial infection. However, the patient's skin lesions are not painful or itchy, which is not typical for cellulitis. Herpes zoster could present with a rash and pain, but the patient's rash is not in a dermatomal distribution and he does not report any changes in taste or hearing, which can occur with herpes zoster. A fungal infection could also cause a rash, but the patient's rapid onset of symptoms and lack of exposure to environments where fungi are commonly found make this less likely. The patient's history of cancer and radiation therapy could potentially make him more susceptible to infections, but his recent lab work does not show any signs of immunosuppression. The patient's worsening symptoms despite treatment with antiviral and antibiotic medications, as well as his new onset of visual hallucinations and confusion, suggest a more serious condition. The most likely diagnosis for this patient is herpes zoster (shingles) with possible central nervous system involvement.\n\nDiagnosis: Herpes Zoster with possible central nervous system involvement.""
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10.1056/NEJMcpc2100273,"Case 11-2021: A 39-Year-Old Woman with Fever, Flank Pain, and Inguinal Lymphadenopathy","Hematocrit (%)   36
Hemoglobin (g/dl)   11.6
White-cell count (per μl)   10,500
Differential count (per μl)
Neutrophils   5910
Lymphocytes   3190
Monocytes   960
Eosinophils   33
Basophils  00 5
Platelet count (per μl)   409,000
Mean corpuscular volume (fl)   85.6
Erythrocyte sedimentation rate 
(mm/hr)
 0 41
C-reactive protein (mg/liter)   100.7",Bartonella henselae infection (cat scratch disease).,Bartonella henselae infection (cat scratch disease).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 39-year-old woman presented to this hospital with fever, flank pain, and tender inguinal lymphadenopathy.
The patient had been in her usual state of health until approximately 4 weeks before admission, when she noted tender bilateral inguinal swelling. Two days later, she began to have sharp, intermittent flank pain on the right side; she rated the pain at 5 on a scale of 0 to 10, with 10 indicating the most severe pain. During the next 3 days, she had nausea and a poor appetite. She noted foul-smelling urine but had no dysuria, urinary frequency, or hematuria.
Three weeks before admission, the patient was evaluated by her primary care physician. On examination, the temperature was 36.6[degrees]C, and she appeared well. There was costovertebral and abdominal tenderness on the right side, without rebound or guarding. The external genitalia were normal. Copious thin, white vaginal discharge was present; no cervical motion tenderness was noted, and the ovaries were normal on palpation. Multiple bilateral tender inguinal lymph nodes, measuring up to 2 cm in diameter, were noted on palpation. The remainder of the physical examination was normal. On microscopic examination of the vaginal discharge, clue cells were observed, but there were no fungal elements or trichomonads. Nucleic acid amplification tests of a cervical swab for Chlamydia trachomatis and Neisseria gonorrhoeae were negative. A blood test for IgM, IgG, and IgA antibodies to C. trachomatis serovars L1 and D through K was negative. Urinalysis revealed leukocyte esterase and nitrates; urine was obtained for culture. Vaginal metronidazole gel was prescribed.
Two days later, the urine culture grew more than 100,000 colony-forming units (CFU) of Escherichia coli per milliliter and 10,000 to 100,000 CFU of Klebsiella pneumoniae per milliliter. A 14-day course of trimethoprim-sulfamethoxazole was prescribed.
The inguinal swelling reportedly abated, but the flank pain and nausea persisted. Two days after the patient completed the prescribed course of trimethoprim-sulfamethoxazole, fever and night sweats developed. After 3 days of fever with a temperature of up to 38.5[degrees]C, she began vomiting and subsequently presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported ongoing flank pain, malaise, nausea, and poor appetite with weight loss of 2.3 kg during the past month. There was no sore throat, cough, or diarrhea. She had a history of hypothyroidism, asthma, bipolar disorder, dysmenorrhea, and migraines. She had had multiple urinary tract infections; pyelonephritis had been diagnosed 4 years before this presentation. A copper intrauterine device had been inserted 6 months before this presentation. Medications included albuterol, budesonide-formoterol, divalproex, levothyroxine, loratadine, and sumatriptan as needed for migraines. The patient did not smoke tobacco, drink alcohol, or use illicit drugs. She had immigrated to the United States from Brazil 1 year earlier; she had been living in New England during the past year and had been working in a laboratory. She had recently spent 3 months in Brazil visiting her husband and had returned to New England shortly before she noted inguinal swelling. While in Brazil, she had remained in a large city and had not visited any remote locations. In New England, she lived alone with one kitten and one full-grown cat. There was no family history of cancer. An aunt had died from tuberculosis, but the patient had had only minimal contact with her aunt.
On examination, the temperature was 36.6[degrees]C, the blood pressure 100/63 mm Hg, the heart rate 77 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The weight was 67.5 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.4. The patient appeared ill. The right side of the abdomen was tender on palpation, without rebound or guarding. Hepatosplenomegaly was not present. Tender bilateral inguinal lymph nodes were noted. No palpable cervical, supraclavicular, infraclavicular, or axillary lymphadenopathy was noted. The remainder of the physical examination was normal. A urine test for human chorionic gonadotropin was negative. Blood levels of glucose, electrolytes, creatine kinase, and lactate dehydrogenase were normal, as were the results of liver-function and kidney-function tests. Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2 were negative, as was an interferon-[gamma] release assay for Mycobacterium tuberculosis. Other laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
Dr. Madeleine Sertic: Computed tomography (CT) of the abdomen and pelvis (Figure 1), performed without the administration of intravenous contrast material, revealed bilateral inguinal lymphadenopathy, with the largest node, on the right side, measuring 2.6 cm in greatest dimension. A right pelvic sidewall lymph node measuring 1.3 cm in greatest dimension, a gastrohepatic lymph node measuring 0.9 cm in greatest dimension, and lymphadenopathy in the porta hepatis were also seen. Transvaginal ultrasonography revealed an intrauterine device in an appropriate position, normal ovaries, and trace free fluid in the pelvis.	
Figure 1 
Dr. Johnson: Intravenous fluids and intramuscular ketorolac were administered, and the patient was admitted to the hospital. A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 39-year-old woman presented to this hospital with fever, flank pain, and tender inguinal lymphadenopathy.
The patient had been in her usual state of health until approximately 4 weeks before admission, when she noted tender bilateral inguinal swelling. Two days later, she began to have sharp, intermittent flank pain on the right side; she rated the pain at 5 on a scale of 0 to 10, with 10 indicating the most severe pain. During the next 3 days, she had nausea and a poor appetite. She noted foul-smelling urine but had no dysuria, urinary frequency, or hematuria.
Three weeks before admission, the patient was evaluated by her primary care physician. On examination, the temperature was 36.6[degrees]C, and she appeared well. There was costovertebral and abdominal tenderness on the right side, without rebound or guarding. The external genitalia were normal. Copious thin, white vaginal discharge was present; no cervical motion tenderness was noted, and the ovaries were normal on palpation. Multiple bilateral tender inguinal lymph nodes, measuring up to 2 cm in diameter, were noted on palpation. The remainder of the physical examination was normal. On microscopic examination of the vaginal discharge, clue cells were observed, but there were no fungal elements or trichomonads. Nucleic acid amplification tests of a cervical swab for Chlamydia trachomatis and Neisseria gonorrhoeae were negative. A blood test for IgM, IgG, and IgA antibodies to C. trachomatis serovars L1 and D through K was negative. Urinalysis revealed leukocyte esterase and nitrates; urine was obtained for culture. Vaginal metronidazole gel was prescribed.
Two days later, the urine culture grew more than 100,000 colony-forming units (CFU) of Escherichia coli per milliliter and 10,000 to 100,000 CFU of Klebsiella pneumoniae per milliliter. A 14-day course of trimethoprim-sulfamethoxazole was prescribed.
The inguinal swelling reportedly abated, but the flank pain and nausea persisted. Two days after the patient completed the prescribed course of trimethoprim-sulfamethoxazole, fever and night sweats developed. After 3 days of fever with a temperature of up to 38.5[degrees]C, she began vomiting and subsequently presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported ongoing flank pain, malaise, nausea, and poor appetite with weight loss of 2.3 kg during the past month. There was no sore throat, cough, or diarrhea. She had a history of hypothyroidism, asthma, bipolar disorder, dysmenorrhea, and migraines. She had had multiple urinary tract infections; pyelonephritis had been diagnosed 4 years before this presentation. A copper intrauterine device had been inserted 6 months before this presentation. Medications included albuterol, budesonide-formoterol, divalproex, levothyroxine, loratadine, and sumatriptan as needed for migraines. The patient did not smoke tobacco, drink alcohol, or use illicit drugs. She had immigrated to the United States from Brazil 1 year earlier; she had been living in New England during the past year and had been working in a laboratory. She had recently spent 3 months in Brazil visiting her husband and had returned to New England shortly before she noted inguinal swelling. While in Brazil, she had remained in a large city and had not visited any remote locations. In New England, she lived alone with one kitten and one full-grown cat. There was no family history of cancer. An aunt had died from tuberculosis, but the patient had had only minimal contact with her aunt.
On examination, the temperature was 36.6[degrees]C, the blood pressure 100/63 mm Hg, the heart rate 77 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The weight was 67.5 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.4. The patient appeared ill. The right side of the abdomen was tender on palpation, without rebound or guarding. Hepatosplenomegaly was not present. Tender bilateral inguinal lymph nodes were noted. No palpable cervical, supraclavicular, infraclavicular, or axillary lymphadenopathy was noted. The remainder of the physical examination was normal. A urine test for human chorionic gonadotropin was negative. Blood levels of glucose, electrolytes, creatine kinase, and lactate dehydrogenase were normal, as were the results of liver-function and kidney-function tests. Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2 were negative, as was an interferon-[gamma] release assay for Mycobacterium tuberculosis. Other laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
Dr. Madeleine Sertic: Computed tomography (CT) of the abdomen and pelvis (Figure 1), performed without the administration of intravenous contrast material, revealed bilateral inguinal lymphadenopathy, with the largest node, on the right side, measuring 2.6 cm in greatest dimension. A right pelvic sidewall lymph node measuring 1.3 cm in greatest dimension, a gastrohepatic lymph node measuring 0.9 cm in greatest dimension, and lymphadenopathy in the porta hepatis were also seen. Transvaginal ultrasonography revealed an intrauterine device in an appropriate position, normal ovaries, and trace free fluid in the pelvis.	
Figure 1 
Dr. Johnson: Intravenous fluids and intramuscular ketorolac were administered, and the patient was admitted to the hospital. A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Tuberculosis (TB) lymphadenitis. The patient's symptoms of fever, flank pain, and tender inguinal lymphadenopathy, along with her history of contact with a relative who died from TB, suggest a possible TB infection. The CT scan showing lymphadenopathy in multiple areas further supports this diagnosis. The patient's recent travel to Brazil, a country with a higher prevalence of TB, also increases the likelihood of this diagnosis. The negative interferon-gamma release assay does not rule out TB, as this test can be negative in active TB infection.""
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        ""content"": ""The patient's symptoms of fever, flank pain, and tender inguinal lymphadenopathy, along with her history of urinary tract infections and recent travel to Brazil, suggest an infectious process. The presence of Escherichia coli and Klebsiella pneumoniae in her urine culture indicates a urinary tract infection, but her symptoms did not improve with antibiotics, suggesting a more complex issue. The patient's ongoing symptoms and the presence of lymphadenopathy in multiple areas (inguinal, pelvic sidewall, gastrohepatic, and porta hepatis) suggest a systemic infection. Given her recent travel to Brazil and contact with cats, one possibility is a zoonotic infection such as cat-scratch disease (Bartonella henselae) or toxoplasmosis. However, these conditions typically present with more specific symptoms such as a papule or pustule at the site of inoculation (cat-scratch disease) or flu-like symptoms and lymphadenopathy (toxoplasmosis). Another possibility is a sexually transmitted infection, but tests for Chlamydia trachomatis and Neisseria gonorrhoeae were negative. The patient's symptoms and test results do not clearly point to a single diagnosis, but the combination of urinary symptoms, lymphadenopathy, and fever suggests a systemic bacterial infection that has not responded to initial antibiotic treatment.\n\nDiagnosis: Refractory urinary tract infection with systemic involvement.""
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        ""content"": ""The patient is a 39-year-old woman with a history of multiple urinary tract infections and recent travel to Brazil. She presents with fever, flank pain, tender inguinal lymphadenopathy, and a history of foul-smelling urine. The differential diagnosis includes urinary tract infection (UTI), pyelonephritis, sexually transmitted infection (STI), and lymphoma. The patient's urine culture grew E. coli and K. pneumoniae, which are common pathogens in UTIs and pyelonephritis. However, despite treatment with trimethoprim-sulfamethoxazole, her symptoms persisted and she developed fever and night sweats, which are not typical for UTIs or pyelonephritis. STIs can cause inguinal lymphadenopathy, but her tests for Chlamydia trachomatis and Neisseria gonorrhoeae were negative. Lymphoma can cause fever, night sweats, weight loss, and lymphadenopathy, but the patient's lack of other symptoms such as fatigue, itching, or other enlarged lymph nodes makes this less likely. The patient's recent travel to Brazil raises the possibility of a tropical infectious disease, but she did not visit any remote locations and her symptoms are not typical for common tropical diseases. The patient's CT scan showed inguinal and pelvic lymphadenopathy, which is not typical for UTIs or pyelonephritis, but could be seen in lymphoma or a systemic infection. Given the patient's persistent symptoms despite treatment for UTI, the presence of lymphadenopathy in multiple sites, and her recent travel history, a systemic infection is the most likely diagnosis.\n\nDiagnosis: Systemic infection.""
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10.1056/NEJMcpc2027090,"Case 10-2021: A 70-Year-Old Man with Depressed Mood, Unsteady Gait, and Urinary Incontinence","Sodium (mmol/liter)   130 136
Potassium (mmol/liter)   4.6 4.4
Chloride (mmol/liter)   92 99
Carbon dioxide (mmol/liter)   25 24
Urea nitrogen (mg/dl)   21 18
Creatinine (mg/dl)   0.99 1.02
Glucose (mg/dl)   77 74
Valproic acid (μg/ml)   66.8 50.8
25-Hydroxyvitamin D (ng/ml) 2 0 27 29
Thyrotropin (μIU/ml) 0.4 0 6.66 3.21
Free thyroxine (ng/dl) 0.9–1.8 1.2 —",Normal pressure hydrocephalus,Normal pressure hydrocephalus,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old man with bipolar disorder was evaluated at this hospital because of depressed mood, suicidal ideation, and gait disturbance.
The patient had a long history of depressive episodes, with two previous hospitalizations for suicide attempts. Approximately two decades before the current admission, he was struck on the head with a beam while working at a construction site and had a 4-cm laceration. He presented to the emergency department of this hospital, where the wound was sutured but no further evaluation was conducted.
Approximately 10 years before the current admission, around the time of his mother's death, the patient was evaluated at this hospital because of an episode of irritability, a reduced need for sleep, and grandiosity; he reported feelings of ""transcendence"" and being ""at one with God."" He was admitted for 1 month to the psychiatry unit of a second hospital, where he was treated with lithium and electroconvulsive therapy. Thereafter, he received outpatient psychiatric treatment on a monthly basis, as well as therapy with valproic acid and fluoxetine.
Approximately 9 years before the current admission, the patient fell on concrete stairs and had back pain with subsequent lower-leg weakness and urinary incontinence. He was evaluated at a third hospital, where magnetic resonance imaging (MRI) of the lumbar spine revealed multilevel degenerative changes, including L4-L5 spinal stenosis and central disk protrusion. Acetaminophen and physical therapy were prescribed.
Five years later (4 years before the current admission), the patient fell because of an unsteady gait and was evaluated at a fourth hospital. Neurologic examination revealed a memory deficit (with an inability to recall any objects after 5 minutes on the three-item object-recall test) and poor attention (with an inability to perform serial sevens calculations), as well as action tremor in the arms and ""mildly unsteady"" gait, even with the use of a cane. The remainder of the physical examination was reportedly normal. The complete blood count, results of renal function tests, and levels of electrolytes, valproic acid, folate, vitamin B12, glycated hemoglobin, and thyrotropin were normal; serum and urine toxicologic panels were negative. MRI of the head reportedly revealed no evidence of an infarct, intracranial hemorrhage, or a mass but showed mild prominence of ventricles, sulci, and cisterns. The dose of fluoxetine was decreased, and the patient was discharged 3 days later.
Additional falls occurred 2 months and 4 months later, and both times, the patient was evaluated at the fourth hospital. Two months after the most recent fall, he hit the car in front of him while driving. His psychiatrist noted that he had bilateral tremor at rest; the dose of valproic acid was reduced, and he was referred to a neurologist. Two months after the car crash, he fell while walking and was evaluated at the fourth hospital. The evaluation was notable for nystagmus and a normal valproic acid level (89 [mu]g per milliliter; reference range, 50 to 100) despite the dose reduction; the doses of valproic acid and trazodone were reduced, and physical therapy was provided. During the next 5 months, gait instability was reduced but persisted. The patient was evaluated by two other neurologists after reporting a feeling of ""imbalance."" Audiometry revealed mild-to-moderate high-frequency sensorineural hearing loss. Medications were considered to be a contributor to his balance dysfunction.
During the next 12 months, the dose of valproic acid was tapered and fluoxetine was stopped; the patient underwent trials of escitalopram and then sertraline for the treatment of depressive symptoms. He reported to his psychiatrist symptoms of confusion, some difficulty with memory, and decreased leg coordination. The Montreal Cognitive Assessment score was 23 (scores range from 0 to 30, with a score of 18 to 25 suggesting mild cognitive impairment).
Dr. McKinley Glover: Fifteen months before the current admission, the patient began to have dizziness. MRI of the head (Figure 1), performed at this hospital, revealed an old infarct in the left corona radiata, features of mild small-vessel disease, mild diffuse brain parenchymal volume loss, and mild ventricular prominence.	
Figure 1 
Dr. Luccarelli: Neuropsychiatric testing was performed, and the results did not suggest a neurodegenerative process. Given the patient's progressively depressed mood, treatment with aripiprazole was started, with the dose adjusted over the following 12 months.
Three months before the current admission, the patient reported worsening depression, with hopelessness, guilt, and increased sleep. That month, his son found him unable to walk and requiring assistance to move. On examination, he had tremor and muscle rigidity; on ambulation, he had a shuffling gait and required a cane. Treatment with aripiprazole was stopped, benztropine was started, and sertraline was replaced by fluoxetine.
One month before the current admission, the patient was voluntarily hospitalized in the psychiatry unit of this hospital because of worsening depression, which he attributed to the progressive reduction in mobility and strength. He reported 3 weeks of frequent early morning awakenings, anhedonia, low energy, anorexia, difficulty concentrating, and low motivation, such that he had not paid bills or bathed. Examination was notable for tremor, muscle rigidity, and a shuffling gait. Blood levels of folate, vitamin B12, and glycated hemoglobin were normal. Other laboratory test results are shown in Table 1. Tests for human immunodeficiency virus types 1 and 2 antibodies and type 1 antigen and for antitreponemal antibodies were negative. Over the 5-day hospitalization, the dose of fluoxetine was increased and treatment with lurasidone was started.	
Table 1 
During the following 4 weeks, the patient's ability to walk continued to deteriorate, and he required intermittent use of a walker and a wheelchair. His depressive symptoms persisted, and after he reported thoughts of suicide and feeling unsafe to his psychiatrist, he was voluntarily admitted to the inpatient psychiatry unit of this hospital. A review of systems was notable for malaise, anorexia, poor sleep, anhedonia, hopelessness, guilt, low energy, worsening gait, and chronic joint pain; he reported no recent falls or manic symptoms.
The patient's psychiatric history included bipolar depression with suicide attempts and multiple psychiatric admissions, obsessive-compulsive disorder, and skin picking. His medical history was notable for long-standing urinary incontinence, hypertension, and sleep apnea; he had undergone laser ablation of the prostate 4 years earlier, as well as bilateral inguinal hernia repair and rotator cuff repair. Medications at the time of admission included fluoxetine, lurasidone, valproic acid, aspirin, and lisinopril, as well as lorazepam and trazodone as needed. Lithium had caused tremor, aripiprazole had caused muscle rigidity and tremor, and gabapentin had caused grogginess. The patient did not smoke tobacco, and he drank alcohol less than once monthly; he had previously smoked marijuana several times daily but had been abstinent for 2 years. He was retired from employment as a laborer. He was divorced and resided in an assisted-living facility. His family history was notable for major depression in his mother and bipolar disorder in one of his children.
The temperature was 36.1[degrees]C, the heart rate 74 beats per minute, the blood pressure 110/61 mm Hg, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.5. The patient was wheelchair-bound. He was described as well-groomed and cooperative, with appropriate eye contact. He was oriented to time, place, and person. His speech was fluent and indicated a logical thought process but was considered to be ""slow."" Some of his responses seemed slow, but naming, repetition, attention, concentration, and memory were intact. His mood and affect were described as depressed, and he had suicidal ideation. Results of cranial nerve examination were normal, except for reduced facial expression. Motor examination showed mildly increased tone in the lower legs and left arm, with bradykinesia, and was otherwise normal. The gait was described as being ""slow to start"" with a ""magnetic quality"" and then as ""shuffling"" for a few steps. The remainder of the neurologic and general physical examinations was normal.
The white-cell count, platelet count, and levels of hemoglobin, calcium, and albumin were normal, as were results of liver-function tests. Other laboratory test results are shown in Table 1.
Dr. Glover: MRI of the head (Figure 2), performed with and without the administration of contrast material, revealed the old infarct in the left corona radiata, features of mild small-vessel disease, and mild diffuse brain parenchymal volume loss with prominence of the ventricles and sylvian fissures. There was no abnormal enhancement. Coronal reformatted images showed a callosal angle (the angle at which the two lateral ventricles meet at the level of the posterior commissure) of 66 degrees.	
Figure 2 
Dr. Luccarelli: Diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old man with bipolar disorder was evaluated at this hospital because of depressed mood, suicidal ideation, and gait disturbance.
The patient had a long history of depressive episodes, with two previous hospitalizations for suicide attempts. Approximately two decades before the current admission, he was struck on the head with a beam while working at a construction site and had a 4-cm laceration. He presented to the emergency department of this hospital, where the wound was sutured but no further evaluation was conducted.
Approximately 10 years before the current admission, around the time of his mother's death, the patient was evaluated at this hospital because of an episode of irritability, a reduced need for sleep, and grandiosity; he reported feelings of ""transcendence"" and being ""at one with God."" He was admitted for 1 month to the psychiatry unit of a second hospital, where he was treated with lithium and electroconvulsive therapy. Thereafter, he received outpatient psychiatric treatment on a monthly basis, as well as therapy with valproic acid and fluoxetine.
Approximately 9 years before the current admission, the patient fell on concrete stairs and had back pain with subsequent lower-leg weakness and urinary incontinence. He was evaluated at a third hospital, where magnetic resonance imaging (MRI) of the lumbar spine revealed multilevel degenerative changes, including L4-L5 spinal stenosis and central disk protrusion. Acetaminophen and physical therapy were prescribed.
Five years later (4 years before the current admission), the patient fell because of an unsteady gait and was evaluated at a fourth hospital. Neurologic examination revealed a memory deficit (with an inability to recall any objects after 5 minutes on the three-item object-recall test) and poor attention (with an inability to perform serial sevens calculations), as well as action tremor in the arms and ""mildly unsteady"" gait, even with the use of a cane. The remainder of the physical examination was reportedly normal. The complete blood count, results of renal function tests, and levels of electrolytes, valproic acid, folate, vitamin B12, glycated hemoglobin, and thyrotropin were normal; serum and urine toxicologic panels were negative. MRI of the head reportedly revealed no evidence of an infarct, intracranial hemorrhage, or a mass but showed mild prominence of ventricles, sulci, and cisterns. The dose of fluoxetine was decreased, and the patient was discharged 3 days later.
Additional falls occurred 2 months and 4 months later, and both times, the patient was evaluated at the fourth hospital. Two months after the most recent fall, he hit the car in front of him while driving. His psychiatrist noted that he had bilateral tremor at rest; the dose of valproic acid was reduced, and he was referred to a neurologist. Two months after the car crash, he fell while walking and was evaluated at the fourth hospital. The evaluation was notable for nystagmus and a normal valproic acid level (89 [mu]g per milliliter; reference range, 50 to 100) despite the dose reduction; the doses of valproic acid and trazodone were reduced, and physical therapy was provided. During the next 5 months, gait instability was reduced but persisted. The patient was evaluated by two other neurologists after reporting a feeling of ""imbalance."" Audiometry revealed mild-to-moderate high-frequency sensorineural hearing loss. Medications were considered to be a contributor to his balance dysfunction.
During the next 12 months, the dose of valproic acid was tapered and fluoxetine was stopped; the patient underwent trials of escitalopram and then sertraline for the treatment of depressive symptoms. He reported to his psychiatrist symptoms of confusion, some difficulty with memory, and decreased leg coordination. The Montreal Cognitive Assessment score was 23 (scores range from 0 to 30, with a score of 18 to 25 suggesting mild cognitive impairment).
Dr. McKinley Glover: Fifteen months before the current admission, the patient began to have dizziness. MRI of the head (Figure 1), performed at this hospital, revealed an old infarct in the left corona radiata, features of mild small-vessel disease, mild diffuse brain parenchymal volume loss, and mild ventricular prominence.	
Figure 1 
Dr. Luccarelli: Neuropsychiatric testing was performed, and the results did not suggest a neurodegenerative process. Given the patient's progressively depressed mood, treatment with aripiprazole was started, with the dose adjusted over the following 12 months.
Three months before the current admission, the patient reported worsening depression, with hopelessness, guilt, and increased sleep. That month, his son found him unable to walk and requiring assistance to move. On examination, he had tremor and muscle rigidity; on ambulation, he had a shuffling gait and required a cane. Treatment with aripiprazole was stopped, benztropine was started, and sertraline was replaced by fluoxetine.
One month before the current admission, the patient was voluntarily hospitalized in the psychiatry unit of this hospital because of worsening depression, which he attributed to the progressive reduction in mobility and strength. He reported 3 weeks of frequent early morning awakenings, anhedonia, low energy, anorexia, difficulty concentrating, and low motivation, such that he had not paid bills or bathed. Examination was notable for tremor, muscle rigidity, and a shuffling gait. Blood levels of folate, vitamin B12, and glycated hemoglobin were normal. Other laboratory test results are shown in Table 1. Tests for human immunodeficiency virus types 1 and 2 antibodies and type 1 antigen and for antitreponemal antibodies were negative. Over the 5-day hospitalization, the dose of fluoxetine was increased and treatment with lurasidone was started.	
Table 1 
During the following 4 weeks, the patient's ability to walk continued to deteriorate, and he required intermittent use of a walker and a wheelchair. His depressive symptoms persisted, and after he reported thoughts of suicide and feeling unsafe to his psychiatrist, he was voluntarily admitted to the inpatient psychiatry unit of this hospital. A review of systems was notable for malaise, anorexia, poor sleep, anhedonia, hopelessness, guilt, low energy, worsening gait, and chronic joint pain; he reported no recent falls or manic symptoms.
The patient's psychiatric history included bipolar depression with suicide attempts and multiple psychiatric admissions, obsessive-compulsive disorder, and skin picking. His medical history was notable for long-standing urinary incontinence, hypertension, and sleep apnea; he had undergone laser ablation of the prostate 4 years earlier, as well as bilateral inguinal hernia repair and rotator cuff repair. Medications at the time of admission included fluoxetine, lurasidone, valproic acid, aspirin, and lisinopril, as well as lorazepam and trazodone as needed. Lithium had caused tremor, aripiprazole had caused muscle rigidity and tremor, and gabapentin had caused grogginess. The patient did not smoke tobacco, and he drank alcohol less than once monthly; he had previously smoked marijuana several times daily but had been abstinent for 2 years. He was retired from employment as a laborer. He was divorced and resided in an assisted-living facility. His family history was notable for major depression in his mother and bipolar disorder in one of his children.
The temperature was 36.1[degrees]C, the heart rate 74 beats per minute, the blood pressure 110/61 mm Hg, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.5. The patient was wheelchair-bound. He was described as well-groomed and cooperative, with appropriate eye contact. He was oriented to time, place, and person. His speech was fluent and indicated a logical thought process but was considered to be ""slow."" Some of his responses seemed slow, but naming, repetition, attention, concentration, and memory were intact. His mood and affect were described as depressed, and he had suicidal ideation. Results of cranial nerve examination were normal, except for reduced facial expression. Motor examination showed mildly increased tone in the lower legs and left arm, with bradykinesia, and was otherwise normal. The gait was described as being ""slow to start"" with a ""magnetic quality"" and then as ""shuffling"" for a few steps. The remainder of the neurologic and general physical examinations was normal.
The white-cell count, platelet count, and levels of hemoglobin, calcium, and albumin were normal, as were results of liver-function tests. Other laboratory test results are shown in Table 1.
Dr. Glover: MRI of the head (Figure 2), performed with and without the administration of contrast material, revealed the old infarct in the left corona radiata, features of mild small-vessel disease, and mild diffuse brain parenchymal volume loss with prominence of the ventricles and sylvian fissures. There was no abnormal enhancement. Coronal reformatted images showed a callosal angle (the angle at which the two lateral ventricles meet at the level of the posterior commissure) of 66 degrees.	
Figure 2 
Dr. Luccarelli: Diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms include depression, suicidal ideation, gait disturbance, tremor, muscle rigidity, and a shuffling gait. These symptoms, along with the MRI findings of mild diffuse brain parenchymal volume loss with prominence of the ventricles and sylvian fissures, suggest a neurodegenerative disorder. The patient's gait disturbance, tremor, and muscle rigidity are characteristic of Parkinson's disease. The patient's depression and cognitive impairment could be due to Parkinson's disease as well, as these are common non-motor symptoms of the disease. The patient's symptoms did not improve with psychiatric medications, further suggesting a neurodegenerative process rather than a purely psychiatric one. \n\nDiagnosis: Parkinson's disease.""
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        ""content"": ""This is a 70-year-old man with a history of bipolar disorder who presents with depressed mood, suicidal ideation, and gait disturbance. His history is significant for multiple falls, tremor, muscle rigidity, and a shuffling gait. He also has a history of head trauma. The differential diagnosis for this patient includes Parkinson's disease, normal pressure hydrocephalus (NPH), and a psychiatric disorder such as major depressive disorder or bipolar disorder. The patient's tremor, muscle rigidity, and shuffling gait are suggestive of Parkinson's disease. However, his MRI does not show the characteristic findings of Parkinson's disease, such as loss of the substantia nigra. The patient's MRI does show mild prominence of ventricles, sulci, and cisterns, which could be indicative of NPH. NPH is characterized by the triad of gait disturbance, dementia, and urinary incontinence, all of which this patient has. The patient's psychiatric history and current depressive symptoms could suggest a psychiatric disorder, but this would not explain his gait disturbance and other neurological symptoms. Given the patient's symptoms and MRI findings, NPH is the most likely diagnosis.\n\nDiagnosis: Normal Pressure Hydrocephalus (NPH)""
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10.1056/NEJMcpc2027094,"Case 9-2021: A 16-Year-Old Boy with Headache, Abdominal Pain, and Hypertension","White-cell count (per μl) 450 ,000 27,140
Differential count (per μl)
Neutrophils 180 100 22,820
Lymphocytes 1200–5200 2330
Monocytes 20 00 1210
Eosinophils 0–1000 110
Basophils  0 550
Hematocrit (%) 37.0–49.0 40.4
Hemoglobin (g/dl) 13.0–16.0 13.0
Platelet count (per μl)   278,000
Lactic acid (mmol/liter)   3.4
Sodium (mmol/liter)   135
Potassium (mmol/liter)   4.9
Chloride (mmol/liter)   99
Carbon dioxide (mmol/liter)   20
Anion gap (mmol/liter)   16
Urea nitrogen (mg/dl)   21
Creatinine (mg/dl)   1.64
Glucose (mg/dl)   241
Aspartate aminotransferase (U/liter)   23
Alanine aminotransferase (U/liter)   22
Alkaline phosphatase (U/liter) 82–331 93
Total bilirubin (mg/dl)  0.9
Protein (g/dl)
Total 6. .3 6.1
Albumin   3.6
Globulin   2.5
Calcium (mg/dl)   8.9
High-sensitivity troponin T (ng/liter)   188",Pheochromocytoma.,Pheochromocytoma with hypertensive emergency.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 16-year-old boy was admitted to this hospital because of headache, nausea, vomiting, and abdominal pain.
The patient had been well until 17 months before this admission, when he began to have episodes of headache and neck pain multiple times per week after an all-terrain vehicle (ATV) accident. Two months later, the patient collided with another adolescent while he was playing soccer, and the episodes of headache and neck pain worsened. He rated the pain at 8 on a scale of 0 to 10, with 10 indicating the most severe pain.
Fifteen months before this admission, the patient was evaluated at the pediatric clinic of another hospital. On examination, the pulse was 95 beats per minute and the blood pressure 117/78 mm Hg. There was mild tenderness in the area of the trapezius muscle. A radiograph of the cervical spine was normal. During the next 15 months, the patient was followed in the pediatric and neurology clinics of the other hospital. Ibuprofen, nortriptyline, sumatriptan, cyclobenzaprine, and diazepam were prescribed, but the headache did not abate. He underwent physical therapy, chiropractic adjustment, massage therapy, and acupuncture, but the symptoms persisted.
Three months before this admission, nausea began to occur during the episodes of headache. The pain became more intense when the patient was lying down or was physically active, resulting in tunnel vision and vomiting; after he vomited, the pain became less intense. He was evaluated at the pediatric clinic of the other hospital. On examination, the pulse was 104 beats per minute and the blood pressure 128/80 mm Hg. At the recommendation of his physicians, the patient stopped participating in all sports.
Two days before this admission, the pain worsened and awoke the patient from sleep. The nausea was constant, and the vomiting occurred two times per day. The patient was unable to attend school because of the symptoms. His parents took him to the pediatric clinic of the other hospital. On examination, the temperature was 36.8[degrees]C, the pulse 115 beats per minute, and the blood pressure 120/64 mm Hg. The height was 183.6 cm, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 27.0. The physical examination was normal. A probable diagnosis of mixed migraines and tension headaches was made. Prednisone, zolmitriptan, and ondansetron were prescribed, and the patient was sent home.
On the day of this admission, the patient had new severe pain on the right side of the abdomen that awoke him from sleep. The headache, neck pain, and nausea were constant. The patient was taken to the emergency department of the other hospital. On examination, the temperature was 36.8[degrees]C, the pulse 160 beats per minute, the blood pressure 239/162 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while he was receiving oxygen through a nasal cannula at a rate of 4 liters per minute. The white-cell count was 22,380 per microliter (reference range at other hospital, 3800 to 10,500), the lactic acid level 2.7 mmol per liter (24 mg per deciliter; reference range, 0.5 to 2.2 mmol per liter [5 to 20 mg per deciliter]), and the creatinine level 1.3 mg per deciliter (115 [mu]mol per liter; reference range, 0.6 to 1.3 mg per deciliter [53 to 115 [mu]mol per liter]). An electrocardiogram (ECG) showed sinus tachycardia with increased R-wave and S-wave amplitudes in the precordial leads, as well as nonspecific repolarization abnormalities. One hour later, a repeat ECG showed an ectopic atrial rhythm with frequent premature ventricular contractions at a rate of 66 beats per minute.
Intravenous hydromorphone, morphine, ondansetron, metoclopramide, and lactated Ringer's solution were administered. A nitroglycerin infusion was started, and the systolic blood pressure decreased to 143 mm Hg; the infusion was stopped, and the systolic blood pressure increased to 212 mm Hg. Intravenous labetalol was administered, and the systolic blood pressure decreased to 92 mm Hg. An esmolol infusion was started, and the patient was transferred to the pediatric intensive care unit (PICU) of this hospital, arriving 3 hours after presentation to the other hospital. Shortly after his arrival, the esmolol infusion was stopped.
On admission to this hospital, additional history was obtained. The patient had played paintball a few days earlier but did not recall any direct trauma to the chest or abdomen. A review of systems was notable for heat intolerance and night sweats. He had a history of acne and had received a diagnosis of pneumonia involving the right upper lobe 10 months before this admission. He had normal growth and development and had received all routine childhood vaccines. His medications included doxycycline and topical tretinoin, clindamycin, and benzoyl peroxide, in addition to zolmitriptan and ondansetron; he had not started taking the recently prescribed prednisone. There were no known drug allergies.
The patient lived in a suburban area of New England with his parents and younger brother. He performed well in high school. Before the recent progression of his symptoms, he had participated in soccer, basketball, and track. He did not smoke tobacco or use illicit drugs. He drank one or two alcoholic beverages per month. His father and paternal grandparents had hypertension, and his maternal aunts had migraines; his mother and brother were healthy.
On examination, the temperature was 36.6[degrees]C, the pulse 126 beats per minute, the blood pressure 90/44 mm Hg, the respiratory rate 15 breaths per minute, and the oxygen saturation 100% while the patient was receiving oxygen through a nasal cannula at a rate of 4 liters per minute. He appeared tired, pale, and diaphoretic. He was in distress because of the pain; he spoke in brief sentences and had frequent hiccups. The abdomen was nondistended with marked tenderness in the right upper quadrant and right flank, with rebound and guarding. The skin was warm and clammy, and some inguinal hyperpigmentation was present. No cafe au lait spots were noted.
The white-cell count was 27,140 per microliter (reference range at this hospital, 4500 to 13,000), the lactic acid level 3.4 mmol per liter (31 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter [5 to 18 mg per deciliter]), the creatinine level 1.64 mg per deciliter (145 [mu]mol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 [mu]mol per liter]), and the high-sensitivity troponin T level 188 ng per liter (reference range, 0 to 14). Additional laboratory test results are shown in Table 1. On hospital day 2, urinalysis revealed 1+ blood, trace ketones, a pH of 5.0, and a specific gravity of 1.015; microscopic examination of the urinary sediment revealed squamous cells, crystals, and mucin, as well as 3 to 5 hyaline casts per high-power field, less than 10 white cells per high-power field, and no red cells.	
Table 1 
A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 16-year-old boy was admitted to this hospital because of headache, nausea, vomiting, and abdominal pain.
The patient had been well until 17 months before this admission, when he began to have episodes of headache and neck pain multiple times per week after an all-terrain vehicle (ATV) accident. Two months later, the patient collided with another adolescent while he was playing soccer, and the episodes of headache and neck pain worsened. He rated the pain at 8 on a scale of 0 to 10, with 10 indicating the most severe pain.
Fifteen months before this admission, the patient was evaluated at the pediatric clinic of another hospital. On examination, the pulse was 95 beats per minute and the blood pressure 117/78 mm Hg. There was mild tenderness in the area of the trapezius muscle. A radiograph of the cervical spine was normal. During the next 15 months, the patient was followed in the pediatric and neurology clinics of the other hospital. Ibuprofen, nortriptyline, sumatriptan, cyclobenzaprine, and diazepam were prescribed, but the headache did not abate. He underwent physical therapy, chiropractic adjustment, massage therapy, and acupuncture, but the symptoms persisted.
Three months before this admission, nausea began to occur during the episodes of headache. The pain became more intense when the patient was lying down or was physically active, resulting in tunnel vision and vomiting; after he vomited, the pain became less intense. He was evaluated at the pediatric clinic of the other hospital. On examination, the pulse was 104 beats per minute and the blood pressure 128/80 mm Hg. At the recommendation of his physicians, the patient stopped participating in all sports.
Two days before this admission, the pain worsened and awoke the patient from sleep. The nausea was constant, and the vomiting occurred two times per day. The patient was unable to attend school because of the symptoms. His parents took him to the pediatric clinic of the other hospital. On examination, the temperature was 36.8[degrees]C, the pulse 115 beats per minute, and the blood pressure 120/64 mm Hg. The height was 183.6 cm, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 27.0. The physical examination was normal. A probable diagnosis of mixed migraines and tension headaches was made. Prednisone, zolmitriptan, and ondansetron were prescribed, and the patient was sent home.
On the day of this admission, the patient had new severe pain on the right side of the abdomen that awoke him from sleep. The headache, neck pain, and nausea were constant. The patient was taken to the emergency department of the other hospital. On examination, the temperature was 36.8[degrees]C, the pulse 160 beats per minute, the blood pressure 239/162 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while he was receiving oxygen through a nasal cannula at a rate of 4 liters per minute. The white-cell count was 22,380 per microliter (reference range at other hospital, 3800 to 10,500), the lactic acid level 2.7 mmol per liter (24 mg per deciliter; reference range, 0.5 to 2.2 mmol per liter [5 to 20 mg per deciliter]), and the creatinine level 1.3 mg per deciliter (115 [mu]mol per liter; reference range, 0.6 to 1.3 mg per deciliter [53 to 115 [mu]mol per liter]). An electrocardiogram (ECG) showed sinus tachycardia with increased R-wave and S-wave amplitudes in the precordial leads, as well as nonspecific repolarization abnormalities. One hour later, a repeat ECG showed an ectopic atrial rhythm with frequent premature ventricular contractions at a rate of 66 beats per minute.
Intravenous hydromorphone, morphine, ondansetron, metoclopramide, and lactated Ringer's solution were administered. A nitroglycerin infusion was started, and the systolic blood pressure decreased to 143 mm Hg; the infusion was stopped, and the systolic blood pressure increased to 212 mm Hg. Intravenous labetalol was administered, and the systolic blood pressure decreased to 92 mm Hg. An esmolol infusion was started, and the patient was transferred to the pediatric intensive care unit (PICU) of this hospital, arriving 3 hours after presentation to the other hospital. Shortly after his arrival, the esmolol infusion was stopped.
On admission to this hospital, additional history was obtained. The patient had played paintball a few days earlier but did not recall any direct trauma to the chest or abdomen. A review of systems was notable for heat intolerance and night sweats. He had a history of acne and had received a diagnosis of pneumonia involving the right upper lobe 10 months before this admission. He had normal growth and development and had received all routine childhood vaccines. His medications included doxycycline and topical tretinoin, clindamycin, and benzoyl peroxide, in addition to zolmitriptan and ondansetron; he had not started taking the recently prescribed prednisone. There were no known drug allergies.
The patient lived in a suburban area of New England with his parents and younger brother. He performed well in high school. Before the recent progression of his symptoms, he had participated in soccer, basketball, and track. He did not smoke tobacco or use illicit drugs. He drank one or two alcoholic beverages per month. His father and paternal grandparents had hypertension, and his maternal aunts had migraines; his mother and brother were healthy.
On examination, the temperature was 36.6[degrees]C, the pulse 126 beats per minute, the blood pressure 90/44 mm Hg, the respiratory rate 15 breaths per minute, and the oxygen saturation 100% while the patient was receiving oxygen through a nasal cannula at a rate of 4 liters per minute. He appeared tired, pale, and diaphoretic. He was in distress because of the pain; he spoke in brief sentences and had frequent hiccups. The abdomen was nondistended with marked tenderness in the right upper quadrant and right flank, with rebound and guarding. The skin was warm and clammy, and some inguinal hyperpigmentation was present. No cafe au lait spots were noted.
The white-cell count was 27,140 per microliter (reference range at this hospital, 4500 to 13,000), the lactic acid level 3.4 mmol per liter (31 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter [5 to 18 mg per deciliter]), the creatinine level 1.64 mg per deciliter (145 [mu]mol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 [mu]mol per liter]), and the high-sensitivity troponin T level 188 ng per liter (reference range, 0 to 14). Additional laboratory test results are shown in Table 1. On hospital day 2, urinalysis revealed 1+ blood, trace ketones, a pH of 5.0, and a specific gravity of 1.015; microscopic examination of the urinary sediment revealed squamous cells, crystals, and mucin, as well as 3 to 5 hyaline casts per high-power field, less than 10 white cells per high-power field, and no red cells.	
Table 1 
A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Pheochromocytoma\n\nThe patient's symptoms of headache, nausea, vomiting, and abdominal pain, along with his history of hypertension, are consistent with pheochromocytoma. This is a rare tumor that develops in the adrenal glands and can cause high blood pressure, rapid heart rate, sweating, and severe headaches. The patient's elevated white blood cell count and lactic acid level also suggest a stress response, which can be caused by a pheochromocytoma. The patient's symptoms worsened with physical activity and improved with rest, which is consistent with the episodic nature of symptoms seen in pheochromocytoma. The patient's high blood pressure and heart rate, along with his elevated troponin T level, suggest that the tumor may be causing a stress response in the heart. The patient's abdominal pain and tenderness in the right upper quadrant and right flank suggest that the tumor may be located in the right adrenal gland.""
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        ""content"": ""The patient's symptoms of headache, nausea, vomiting, and abdominal pain, along with a history of hypertension in the family, suggest a possible cardiovascular issue. The patient's high blood pressure and tachycardia, along with the elevated white cell count and lactic acid level, suggest a possible infection or inflammation. The patient's abdominal pain and the presence of blood in the urine suggest a possible kidney issue. The patient's history of an ATV accident and a collision during a soccer game suggest a possible injury that may have caused damage to the kidneys or other organs. The patient's symptoms did not improve with various treatments for headache, suggesting that the cause of the symptoms is not a simple headache or tension. The patient's symptoms worsened when lying down or being physically active, suggesting a possible issue with blood flow or pressure in the body. The patient's symptoms of heat intolerance and night sweats, along with the presence of hyperpigmentation in the inguinal area, suggest a possible endocrine issue. The patient's elevated troponin T level suggests possible damage to the heart. Considering all these factors, the most likely diagnosis is pheochromocytoma, a rare tumor of the adrenal glands that can cause high blood pressure, headaches, sweating, and symptoms of a panic attack.\n\nDiagnosis: Pheochromocytoma.""
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        ""content"": ""The patient is a 16-year-old boy presenting with severe headache, nausea, vomiting, and abdominal pain. His symptoms began after an ATV accident and worsened after a collision during a soccer game. His symptoms have persisted despite various treatments and have recently worsened, with the addition of constant nausea and new severe abdominal pain. His physical examination is notable for marked tenderness in the right upper quadrant and right flank, with rebound and guarding. His lab results show an elevated white cell count, lactic acid level, creatinine level, and high-sensitivity troponin T level. \n\nThe differential diagnosis for this patient includes migraines, tension headaches, concussion or other traumatic brain injury, intracranial hypertension, and abdominal conditions such as appendicitis, cholecystitis, or kidney stones. Given the patient's history of trauma, a concussion or other traumatic brain injury could be possible, but these would not typically cause the severe abdominal pain the patient is experiencing. Migraines and tension headaches could explain the patient's headaches, but again, would not typically cause severe abdominal pain. Intracranial hypertension could potentially cause both headaches and nausea/vomiting, but would not typically cause abdominal pain. Appendicitis or cholecystitis could potentially cause both abdominal pain and systemic symptoms such as nausea and vomiting, but would not typically cause headaches. Kidney stones could potentially cause both abdominal pain and systemic symptoms, but again, would not typically cause headaches.\n\nGiven the patient's severe abdominal pain and the findings on physical examination, an abdominal condition seems most likely. The patient's elevated white cell count and lactic acid level suggest an acute inflammatory or infectious process. His elevated creatinine level suggests possible kidney involvement, and his elevated high-sensitivity troponin T level suggests possible heart involvement. \n\nThe patient's symptoms, physical examination findings, and lab results are most consistent with a diagnosis of pheochromocytoma. This is a rare tumor that develops in the adrenal glands and produces excess amounts of adrenaline and noradrenaline, which can cause symptoms such as severe headaches, high blood pressure, rapid heartbeat, sweating, and abdominal pain. The patient's history of heat intolerance and night sweats, as well as his elevated blood pressure and heart rate, are also consistent with this diagnosis.\n\nDiagnosis: Pheochromocytoma.""
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10.1056/NEJMcpc2027092,Case 8-2021: A 34-Year-Old Woman with Cholangiocarcinoma,,Intrahepatic cholangiocarcinoma.,Intrahepatic cholangiocarcinoma.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 34-year-old woman was evaluated in the oncology clinic of this hospital for the management of relapsed, metastatic intrahepatic cholangiocarcinoma.
The patient had been well until 3 years before this evaluation, when acute abdominal and back pain developed, and she presented to the emergency department of another hospital. As part of the evaluation, abdominal ultrasonography was performed and reportedly revealed a lesion in the right lobe of the liver. Additional imaging studies were obtained.
Dr. Theodore T. Pierce: Magnetic resonance imaging (MRI) revealed a heterogeneous, hypoenhancing, lobulated lesion that measured 6.1 cm by 4.5 cm (Figure 1A), with imaging characteristics suggestive of primary or metastatic cancer. The lesion was associated with peripheral biliary dilatation, which suggested biliary obstruction (Figure 1B); restricted diffusion, indicating high tissue density (Figure 1C); peripheral rim enhancement on arterial phase imaging, reflecting increased vascularity at the rim of the lesion (Figure 1D); and delayed enhancement of the more central areas of the lesion, indicating fibrosis (Figure 1E and 1F). Taken together, these features are atypical of benign lesions, such as hemangiomas, focal nodular hyperplasia, and hepatic adenoma, and are most consistent with cholangiocarcinoma.	
Figure 1 Figure 1Opens a popup window	Opens a popup window	Opens a popup window
Positron-emission tomography and computed tomography (PET-CT), performed after the administration of intravenous 18F-fluorodeoxyglucose (FDG) tracer, revealed FDG avidity in the hepatic mass in the right lobe. No additional sites of hypermetabolism were noted.
Dr. Chen: Given the concern for cancer, blood samples were obtained for testing for tumor markers. The level of CA 19-9 was elevated, at 110 IU per milliliter (reference value, <35), but the levels of alpha-fetoprotein and carcinoembryonic antigen were normal. An ultrasound-guided core-needle biopsy of the liver mass in the right lobe was performed, and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 34-year-old woman was evaluated in the oncology clinic of this hospital for the management of relapsed, metastatic intrahepatic cholangiocarcinoma.
The patient had been well until 3 years before this evaluation, when acute abdominal and back pain developed, and she presented to the emergency department of another hospital. As part of the evaluation, abdominal ultrasonography was performed and reportedly revealed a lesion in the right lobe of the liver. Additional imaging studies were obtained.
Dr. Theodore T. Pierce: Magnetic resonance imaging (MRI) revealed a heterogeneous, hypoenhancing, lobulated lesion that measured 6.1 cm by 4.5 cm (Figure 1A), with imaging characteristics suggestive of primary or metastatic cancer. The lesion was associated with peripheral biliary dilatation, which suggested biliary obstruction (Figure 1B); restricted diffusion, indicating high tissue density (Figure 1C); peripheral rim enhancement on arterial phase imaging, reflecting increased vascularity at the rim of the lesion (Figure 1D); and delayed enhancement of the more central areas of the lesion, indicating fibrosis (Figure 1E and 1F). Taken together, these features are atypical of benign lesions, such as hemangiomas, focal nodular hyperplasia, and hepatic adenoma, and are most consistent with cholangiocarcinoma.	
Figure 1 Figure 1Opens a popup window	Opens a popup window	Opens a popup window
Positron-emission tomography and computed tomography (PET-CT), performed after the administration of intravenous 18F-fluorodeoxyglucose (FDG) tracer, revealed FDG avidity in the hepatic mass in the right lobe. No additional sites of hypermetabolism were noted.
Dr. Chen: Given the concern for cancer, blood samples were obtained for testing for tumor markers. The level of CA 19-9 was elevated, at 110 IU per milliliter (reference value, <35), but the levels of alpha-fetoprotein and carcinoembryonic antigen were normal. An ultrasound-guided core-needle biopsy of the liver mass in the right lobe was performed, and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with acute abdominal and back pain and was found to have a lesion in the right lobe of the liver. MRI imaging revealed characteristics consistent with primary or metastatic cancer, specifically cholangiocarcinoma. PET-CT scan confirmed FDG avidity in the hepatic mass with no additional sites of hypermetabolism. Blood tests showed elevated levels of CA 19-9, a tumor marker often associated with cholangiocarcinoma, while levels of alpha-fetoprotein and carcinoembryonic antigen were normal. An ultrasound-guided core-needle biopsy of the liver mass was performed to confirm the diagnosis.\n\nDiagnosis: Metastatic intrahepatic cholangiocarcinoma.""
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        ""content"": ""The patient is a 34-year-old woman presenting with a history of acute abdominal and back pain. Imaging studies revealed a heterogeneous, hypoenhancing, lobulated lesion in the right lobe of the liver. The lesion was associated with peripheral biliary dilatation, restricted diffusion, peripheral rim enhancement on arterial phase imaging, and delayed enhancement of the more central areas of the lesion. These features are atypical of benign lesions and are most consistent with cholangiocarcinoma. Further, PET-CT revealed FDG avidity in the hepatic mass in the right lobe with no additional sites of hypermetabolism noted. Blood samples showed an elevated level of CA 19-9, a tumor marker often associated with cholangiocarcinoma, while the levels of alpha-fetoprotein and carcinoembryonic antigen were normal. An ultrasound-guided core-needle biopsy of the liver mass in the right lobe was performed. Given the imaging findings, elevated CA 19-9, and the patient's symptoms, the most likely diagnosis is cholangiocarcinoma.\n\nDiagnosis: Cholangiocarcinoma.""
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10.1056/NEJMcpc2027093,"Case 7-2021: A 19-Year-Old Man with Shock, Multiple Organ Failure, and Rash","Hematocrit (%)   48.8
Hemoglobin (g/dl)   16.4
White-cell count (per μl) 450 ,000 7930
Differential count (per μl)
Neutrophils   4591
Bands  00 761
Lymphocytes   420
Eosinophils   206
Basophils  00 71
Myelocytes 0 698
Metamyelocytes 0 1182
Red-cell count (per μl) 4,000,000–5,200,000 5,380,000
Smear description Toxic granulation, Döhle bodies, 
vacuolated neutrophils, 
burr cells
Platelet count (per μl)   12,000
Erythrocyte sedimentation rate (mm/hr)  0 2
Prothrombin time (sec)   69.9
Prothrombin-time international normalized ratio   7.9
Activated partial-thromboplastin time (sec) 22. 6.0 >150.0
Sodium (mmol/liter)   152
Potassium (mmol/liter)   3.4
Chloride (mmol/liter)   107
Carbon dioxide (mmol/liter)   25
Anion gap (mmol/liter)   20
Calcium (mg/dl)   6.1
Phosphorus (mg/dl)   2.7
Magnesium (mg/dl)   1.1
Urea nitrogen (mg/dl)   15
Creatinine (mg/dl)   2.31
Glucose (mg/dl)   82
Protein (g/dl)
Total 6. .3 2.7
Albumin   1.6
Globulin   1.1
Aspartate aminotransferase (U/liter)   31
Alanine aminotransferase (U/liter)   14
Alkaline phosphatase (U/liter)   120
Bilirubin (mg/dl)
Total  2.5
Direct 0.  2.2
Lactic acid (mmol/liter)        9.4                                                                                     d-Dimer (ng/ml)   >10,000
C-reactive protein (mg/liter)  .0 81.4
Fibrinogen (mg/dl) 15 0 <60
Antithrombin III activity (%) 8 0 28
Protein C activity (%) 7 0 5
Protein S activity (%) 7 0 25
Lupus anticoagulant screen Negative Positive
Venous blood gases
Fraction of inspired oxygen 0.60
pH   7.17
Partial pressure of carbon dioxide (mm Hg)   74
Partial pressure of oxygen (mm Hg)   <28
Base excess (mmol/liter) ‚àí4.7",Meningococcal purpura fulminans.,Purpura fulminans due to meningococcemia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 19-year-old man was admitted to the pediatric intensive care unit (PICU) of this hospital because of shock, multiple organ failure, and rash.
The patient had been well until 20 hours before this admission, when diffuse abdominal pain and nausea developed after he ate rice, chicken, and lo mein leftovers from a restaurant meal. Multiple episodes of emesis occurred, with vomitus that was either bilious or red-brown. The abdominal pain and vomiting were followed by the development of chills, generalized weakness, progressively worsening diffuse myalgias, chest pain, shortness of breath, headache, neck stiffness, and blurry vision. Five hours before this admission, purplish discoloration of the skin developed, and a friend took the patient to the emergency department of another hospital for evaluation.
On arrival at the emergency department of the other hospital, 4.5 hours before this admission, the patient reported diffuse myalgias that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. On examination, he appeared pale, anxious, and moderately distressed; he answered questions appropriately and was oriented to person, place, time, and situation. The temperature was 37.4[degrees]C, the pulse 147 beats per minute, the blood pressure 154/124 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. The oral mucous membranes were dry. On auscultation of the heart, tachycardia was present with a regular rhythm. The radial pulses were normal. The lungs were clear, without crackles, rhonchi, or wheezes. The abdomen was soft and nondistended, without tenderness; the patient vomited yellow-green material during the examination. The skin was warm and dry and had a mottled appearance.
Blood specimens were obtained and sent to the laboratory for culture, a complete blood count, and tests of renal function, liver function, and coagulation, as well as measurement of levels of electrolytes, glucose, lipase, lactic acid, and troponin. A urine specimen was sent for urinalysis and culture, and a nasopharyngeal swab was obtained for influenza virus nucleic acid testing. Approximately 40 minutes after the patient's arrival at the other hospital, ondansetron, ceftriaxone, and a 2-liter bolus of 0.90% normal saline were administered intravenously.
During the next 30 minutes, tachypnea worsened and labored breathing, hypoxemia, and cyanosis developed. Supplemental oxygen was administered through a nonrebreather face mask, resulting in an oxygen saturation of 83%; then, oxygen was administered through a high-flow nasal cannula at a rate of 40 liters per minute. Intravenous doses of dexamethasone and vancomycin were given.
During the following 40 minutes, the systolic blood pressure fell to 70 mm Hg and the dorsalis pedis pulses were noted to be weak. Approximately 110 minutes after the patient's arrival at the other hospital, a triple-lumen central venous catheter was placed in the right femoral vein and a continuous intravenous infusion of norepinephrine was initiated. After intravenous doses of midazolam, etomidate, and fentanyl were administered, tracheal intubation was performed and mechanical ventilation with pressure-regulated volume control was begun, with a tidal volume of 6 ml per kilogram of body weight, a rate of 24 breaths per minute, a positive end-expiratory pressure of 10 cm of water, and a fraction of inspired oxygen (Fio2) of 100%. A continuous infusion of propofol was begun.
Hypotension persisted, and a diffuse purpuric rash developed. Approximately 2 hours after the patient's arrival at the other hospital, a dose of piperacillin-tazobactam was administered, a 1-liter bolus of 0.45% normal saline with 150 meq of sodium bicarbonate was given, and a Foley catheter was inserted. Twenty minutes later, a continuous intravenous infusion of phenylephrine was added, followed 7 minutes later by a vasopressin infusion. The patient was transported by helicopter to the PICU of this hospital.
On the patient's admission to this hospital, additional history was obtained from family members. A friend who had eaten the same meal as the patient the evening before admission had vomited once shortly thereafter but had not become progressively ill. The patient had a history of anxiety and depression, as well as intermittent ear infections during childhood. He had no known drug allergies. He had reportedly received all routine childhood vaccinations. He smoked two packs of cigarettes weekly, smoked marijuana daily, and drank two alcoholic beverages approximately 2 times per week. He used dextromethorphan and diphenhydramine recreationally but did not use other illicit drugs.
The patient lived in northern New England with his mother, brother, and three cats but had been staying with a friend for 5 days before admission, during which time he had visited a beach along the ocean and a music venue. He worked part-time at a restaurant; he had not traveled recently or had any other exposure to animals or ill persons. His father had coronary artery disease, his mother had hypothyroidism, and his brother had had viral meningitis at 6 weeks of age.
On examination, the patient was pharmacologically sedated. The temperature was 40.8[degrees]C, the pulse 166 beats per minute, the blood pressure 120/53 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 95% while he was receiving mechanical ventilation with an Fio2 of 50%. He opened his eyes occasionally. The pupils were equal and reactive to light. The femoral pulses were palpable, but the peripheral pulses were not palpable and the digits were cold. There was diffuse anasarca and oozing from venipuncture sites and from the site of central venous catheter insertion. A diffuse reticular purpuric rash was present on the face, chest, abdomen, back, arms, and legs, sparing the palms and soles (Fig. 1). A Foley catheter was in place, without urine output. Laboratory test results are shown in Table 1. Chest radiography revealed perihilar airspace and diffuse interstitial opacities and bilateral small, layering pleural effusions.	
Figure 1
Dr. Manuella Lahoud-Rahme: A transthoracic echocardiogram was obtained while the patient was receiving norepinephrine, epinephrine, and vasopressin. The left ventricle had moderate dysfunction with regional wall-motion abnormalities; septal motion was decreased, but apical motion appeared to be preserved. The right ventricle had mild-to-moderate dysfunction with underfilling. There was no pericardial effusion.
Dr. Lucas: Approximately 7 hours after admission to this hospital, a diagnostic test result was received and additional management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 19-year-old man was admitted to the pediatric intensive care unit (PICU) of this hospital because of shock, multiple organ failure, and rash.
The patient had been well until 20 hours before this admission, when diffuse abdominal pain and nausea developed after he ate rice, chicken, and lo mein leftovers from a restaurant meal. Multiple episodes of emesis occurred, with vomitus that was either bilious or red-brown. The abdominal pain and vomiting were followed by the development of chills, generalized weakness, progressively worsening diffuse myalgias, chest pain, shortness of breath, headache, neck stiffness, and blurry vision. Five hours before this admission, purplish discoloration of the skin developed, and a friend took the patient to the emergency department of another hospital for evaluation.
On arrival at the emergency department of the other hospital, 4.5 hours before this admission, the patient reported diffuse myalgias that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. On examination, he appeared pale, anxious, and moderately distressed; he answered questions appropriately and was oriented to person, place, time, and situation. The temperature was 37.4[degrees]C, the pulse 147 beats per minute, the blood pressure 154/124 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. The oral mucous membranes were dry. On auscultation of the heart, tachycardia was present with a regular rhythm. The radial pulses were normal. The lungs were clear, without crackles, rhonchi, or wheezes. The abdomen was soft and nondistended, without tenderness; the patient vomited yellow-green material during the examination. The skin was warm and dry and had a mottled appearance.
Blood specimens were obtained and sent to the laboratory for culture, a complete blood count, and tests of renal function, liver function, and coagulation, as well as measurement of levels of electrolytes, glucose, lipase, lactic acid, and troponin. A urine specimen was sent for urinalysis and culture, and a nasopharyngeal swab was obtained for influenza virus nucleic acid testing. Approximately 40 minutes after the patient's arrival at the other hospital, ondansetron, ceftriaxone, and a 2-liter bolus of 0.90% normal saline were administered intravenously.
During the next 30 minutes, tachypnea worsened and labored breathing, hypoxemia, and cyanosis developed. Supplemental oxygen was administered through a nonrebreather face mask, resulting in an oxygen saturation of 83%; then, oxygen was administered through a high-flow nasal cannula at a rate of 40 liters per minute. Intravenous doses of dexamethasone and vancomycin were given.
During the following 40 minutes, the systolic blood pressure fell to 70 mm Hg and the dorsalis pedis pulses were noted to be weak. Approximately 110 minutes after the patient's arrival at the other hospital, a triple-lumen central venous catheter was placed in the right femoral vein and a continuous intravenous infusion of norepinephrine was initiated. After intravenous doses of midazolam, etomidate, and fentanyl were administered, tracheal intubation was performed and mechanical ventilation with pressure-regulated volume control was begun, with a tidal volume of 6 ml per kilogram of body weight, a rate of 24 breaths per minute, a positive end-expiratory pressure of 10 cm of water, and a fraction of inspired oxygen (Fio2) of 100%. A continuous infusion of propofol was begun.
Hypotension persisted, and a diffuse purpuric rash developed. Approximately 2 hours after the patient's arrival at the other hospital, a dose of piperacillin-tazobactam was administered, a 1-liter bolus of 0.45% normal saline with 150 meq of sodium bicarbonate was given, and a Foley catheter was inserted. Twenty minutes later, a continuous intravenous infusion of phenylephrine was added, followed 7 minutes later by a vasopressin infusion. The patient was transported by helicopter to the PICU of this hospital.
On the patient's admission to this hospital, additional history was obtained from family members. A friend who had eaten the same meal as the patient the evening before admission had vomited once shortly thereafter but had not become progressively ill. The patient had a history of anxiety and depression, as well as intermittent ear infections during childhood. He had no known drug allergies. He had reportedly received all routine childhood vaccinations. He smoked two packs of cigarettes weekly, smoked marijuana daily, and drank two alcoholic beverages approximately 2 times per week. He used dextromethorphan and diphenhydramine recreationally but did not use other illicit drugs.
The patient lived in northern New England with his mother, brother, and three cats but had been staying with a friend for 5 days before admission, during which time he had visited a beach along the ocean and a music venue. He worked part-time at a restaurant; he had not traveled recently or had any other exposure to animals or ill persons. His father had coronary artery disease, his mother had hypothyroidism, and his brother had had viral meningitis at 6 weeks of age.
On examination, the patient was pharmacologically sedated. The temperature was 40.8[degrees]C, the pulse 166 beats per minute, the blood pressure 120/53 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 95% while he was receiving mechanical ventilation with an Fio2 of 50%. He opened his eyes occasionally. The pupils were equal and reactive to light. The femoral pulses were palpable, but the peripheral pulses were not palpable and the digits were cold. There was diffuse anasarca and oozing from venipuncture sites and from the site of central venous catheter insertion. A diffuse reticular purpuric rash was present on the face, chest, abdomen, back, arms, and legs, sparing the palms and soles (Fig. 1). A Foley catheter was in place, without urine output. Laboratory test results are shown in Table 1. Chest radiography revealed perihilar airspace and diffuse interstitial opacities and bilateral small, layering pleural effusions.	
Figure 1
Dr. Manuella Lahoud-Rahme: A transthoracic echocardiogram was obtained while the patient was receiving norepinephrine, epinephrine, and vasopressin. The left ventricle had moderate dysfunction with regional wall-motion abnormalities; septal motion was decreased, but apical motion appeared to be preserved. The right ventricle had mild-to-moderate dysfunction with underfilling. There was no pericardial effusion.
Dr. Lucas: Approximately 7 hours after admission to this hospital, a diagnostic test result was received and additional management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of abdominal pain, nausea, vomiting, chills, generalized weakness, myalgias, chest pain, shortness of breath, headache, neck stiffness, blurry vision, and purplish discoloration of the skin, along with the rapid progression of his condition, suggest a severe systemic infection. The fact that his friend, who ate the same meal, also vomited but did not become progressively ill, suggests that the patient's condition is not due to food poisoning. The patient's rapid deterioration, including shock, multiple organ failure, and rash, along with the development of a purpuric rash, are suggestive of a severe bacterial infection, such as meningococcal septicemia. Meningococcal septicemia can cause rapid onset of symptoms and can lead to shock and multiple organ failure. The patient's symptoms of neck stiffness and blurry vision could be indicative of meningitis, which can occur in conjunction with meningococcal septicemia. \n\nDiagnosis: Meningococcal septicemia.""
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10.1056/NEJMcpc2027089,"Case 6-2021: A 65-Year-Old Man with Eye Pain and Decreased Vision
","Hemoglobin (g/dl)   12.5
Hematocrit (%)   39.8
Platelet count (per μl)   131,000
White-cell count (per μl)   8090
Differential count (per μl)
Neutrophils   4290
Lymphocytes   2990
Monocytes   650
Eosinophils   80
Basophils  00 80
Erythrocyte sedimentation rate 
(mm/hr)
 0 19
Prothrombin time (sec)   12.9
Prothrombin-time international 
normalized ratio
  1.0
IgG (mg/dl)   951
IgA (mg/dl)   23
IgM (mg/dl)   540
Serum protein electrophoresis No M component IgM kappa M component in the 
gamma region 
at a level of 
0.36 g/dl
Kappa light chain (mg/dl)   145.1
Lambda light chain (mg/dl)   11.4",Lymphoplasmacytic lymphoma of the central nervous system (Bing‚Äö√Ñ√¨Neel syndrom,Bing–Neel syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 65-year-old man was admitted to this hospital because of bilateral eye pain and decreased vision.
The patient had been in his usual state of health until 8 days before this admission, when constant aching pain developed in the left eye and the left side of the head. During the next few days, the vision in the left eye gradually became blurry. Three days before this admission, redness developed in the right eye. The patient used tetrahydrozoline eye drops, but symptoms did not abate. One day before this admission, pain developed in the right eye that was similar to the pain in the left eye. The patient sought evaluation by his primary care physician, who recommended that he present to the emergency department of this hospital for further evaluation.
On arrival, the patient rated the eye pain and headache at 2 on a scale of 0 to 10 (with 10 indicating the most severe pain). The pain was not worse with eye movement or accompanied by flashing lights, floaters, or discharge. The patient reported no trauma but noted weight loss of 4.5 kg in the past 2 weeks, as well as pain with chewing food. He did not have scalp tenderness, fever, chills, nausea, vomiting, numbness, weakness, or slurred speech.
The patient had a history of Waldenstrom's macroglobulinemia, which had been diagnosed 2 years before this admission and treated with plasmapheresis, dexamethasone, and four cycles of bortezomib (with discontinuation of bortezomib after 4 months because of peripheral neuropathy), as well as six cycles of bendamustine. During the 9 months that followed the completion of treatment with bendamustine, there was active surveillance of the blood IgM level. One month before this admission, the IgM level was 1001 mg per deciliter (reference range, 53 to 334), and biopsy of the bone marrow revealed persistent disease. One week before this admission, the patient took his first dose of ibrutinib, which had been prescribed 3 months earlier.
Other medical history included latent tuberculosis, depression, anxiety, prediabetes, folate deficiency, and seasonal allergies. Medications included ibrutinib, isoniazid, pyridoxine, sertraline, citalopram, hydroxyzine, cetirizine, fluticasone nasal spray, and a multivitamin. Rituximab had caused anaphylaxis. The patient did not smoke tobacco, use illicit drugs, or drink alcohol. He was originally from Central America and had immigrated to the United States 50 years earlier; 1 month earlier, he had moved from the West Coast to an urban area of New England. He lived in an apartment with his niece and cousins and worked in construction. His family history was unknown.
On examination, the temperature was 36.3[degrees]C, the blood pressure 104/69 mm Hg, the pulse 60 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. Visual acuity was 20/20 in the right eye and 20/100 in the left eye with correction. On confrontation testing, visual fields in the left eye were deficient in the inferior temporal and nasal aspects. On the Ishihara color test, all plates were identified with the right eye but only the control plate was identified with the left eye. The pupils were symmetric and reactive to light; an afferent pupillary defect was present in the left eye. There was no proptosis. Subconjunctival hemorrhage was present in the right eye; pterygia were present in both eyes. On funduscopic examination, the optic disk in the left eye was edematous. Results of tests of cranial nerve function, power, sensation, reflexes, coordination, and gait were normal.
The blood hemoglobin level was 12.5 g per deciliter (reference range, 13.5 to 17.5), the hematocrit 39.8% (reference range, 41.0 to 53.0), the white-cell count 8090 per microliter (reference range, 4500 to 11,000), and the platelet count 131,000 per microliter (reference range, 150,000 to 400,000). The IgM level was 540 mg per deciliter; the level of IgM kappa M component in the gamma region was 0.36 g per deciliter. Blood levels of electrolytes were normal, as were the results of tests of kidney and liver function. Tests for Lyme disease, syphilis, toxoplasmosis, and bartonellosis were negative. Tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2 were negative. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Javier M. Romero: Computed tomography (CT) of the head, performed with and without the administration of intravenous contrast material, revealed mild thickening and perineural enhancement along the entire length of the left optic nerve (Figure 1A and 1B). There was a deformity of the left lamina papyracea with medial deviation of the medial and superior rectus muscle, as well as postoperative changes in the sinuses. Magnetic resonance imaging (MRI) of the head and orbits, performed with and without the administration of contrast material, was limited by artifact but revealed increased signal intensity and possible focal enhancement within the retrobulbar segment of the left optic nerve (Figure 1C and 1D).	
Figure 1 
Dr. Chwalisz: The patient was admitted to this hospital, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 65-year-old man was admitted to this hospital because of bilateral eye pain and decreased vision.
The patient had been in his usual state of health until 8 days before this admission, when constant aching pain developed in the left eye and the left side of the head. During the next few days, the vision in the left eye gradually became blurry. Three days before this admission, redness developed in the right eye. The patient used tetrahydrozoline eye drops, but symptoms did not abate. One day before this admission, pain developed in the right eye that was similar to the pain in the left eye. The patient sought evaluation by his primary care physician, who recommended that he present to the emergency department of this hospital for further evaluation.
On arrival, the patient rated the eye pain and headache at 2 on a scale of 0 to 10 (with 10 indicating the most severe pain). The pain was not worse with eye movement or accompanied by flashing lights, floaters, or discharge. The patient reported no trauma but noted weight loss of 4.5 kg in the past 2 weeks, as well as pain with chewing food. He did not have scalp tenderness, fever, chills, nausea, vomiting, numbness, weakness, or slurred speech.
The patient had a history of Waldenstrom's macroglobulinemia, which had been diagnosed 2 years before this admission and treated with plasmapheresis, dexamethasone, and four cycles of bortezomib (with discontinuation of bortezomib after 4 months because of peripheral neuropathy), as well as six cycles of bendamustine. During the 9 months that followed the completion of treatment with bendamustine, there was active surveillance of the blood IgM level. One month before this admission, the IgM level was 1001 mg per deciliter (reference range, 53 to 334), and biopsy of the bone marrow revealed persistent disease. One week before this admission, the patient took his first dose of ibrutinib, which had been prescribed 3 months earlier.
Other medical history included latent tuberculosis, depression, anxiety, prediabetes, folate deficiency, and seasonal allergies. Medications included ibrutinib, isoniazid, pyridoxine, sertraline, citalopram, hydroxyzine, cetirizine, fluticasone nasal spray, and a multivitamin. Rituximab had caused anaphylaxis. The patient did not smoke tobacco, use illicit drugs, or drink alcohol. He was originally from Central America and had immigrated to the United States 50 years earlier; 1 month earlier, he had moved from the West Coast to an urban area of New England. He lived in an apartment with his niece and cousins and worked in construction. His family history was unknown.
On examination, the temperature was 36.3[degrees]C, the blood pressure 104/69 mm Hg, the pulse 60 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. Visual acuity was 20/20 in the right eye and 20/100 in the left eye with correction. On confrontation testing, visual fields in the left eye were deficient in the inferior temporal and nasal aspects. On the Ishihara color test, all plates were identified with the right eye but only the control plate was identified with the left eye. The pupils were symmetric and reactive to light; an afferent pupillary defect was present in the left eye. There was no proptosis. Subconjunctival hemorrhage was present in the right eye; pterygia were present in both eyes. On funduscopic examination, the optic disk in the left eye was edematous. Results of tests of cranial nerve function, power, sensation, reflexes, coordination, and gait were normal.
The blood hemoglobin level was 12.5 g per deciliter (reference range, 13.5 to 17.5), the hematocrit 39.8% (reference range, 41.0 to 53.0), the white-cell count 8090 per microliter (reference range, 4500 to 11,000), and the platelet count 131,000 per microliter (reference range, 150,000 to 400,000). The IgM level was 540 mg per deciliter; the level of IgM kappa M component in the gamma region was 0.36 g per deciliter. Blood levels of electrolytes were normal, as were the results of tests of kidney and liver function. Tests for Lyme disease, syphilis, toxoplasmosis, and bartonellosis were negative. Tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2 were negative. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Javier M. Romero: Computed tomography (CT) of the head, performed with and without the administration of intravenous contrast material, revealed mild thickening and perineural enhancement along the entire length of the left optic nerve (Figure 1A and 1B). There was a deformity of the left lamina papyracea with medial deviation of the medial and superior rectus muscle, as well as postoperative changes in the sinuses. Magnetic resonance imaging (MRI) of the head and orbits, performed with and without the administration of contrast material, was limited by artifact but revealed increased signal intensity and possible focal enhancement within the retrobulbar segment of the left optic nerve (Figure 1C and 1D).	
Figure 1 
Dr. Chwalisz: The patient was admitted to this hospital, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of bilateral eye pain, decreased vision, and headache, along with the findings of optic disk edema in the left eye and perineural enhancement along the left optic nerve on CT, suggest optic neuritis. The patient's history of Waldenstrom's macroglobulinemia, a type of non-Hodgkin lymphoma, raises the possibility of a paraneoplastic syndrome or direct infiltration of the optic nerve by lymphoma cells. However, the patient's recent initiation of ibrutinib, a Bruton's tyrosine kinase inhibitor used in the treatment of several B-cell malignancies including Waldenstrom's macroglobulinemia, is notable. Ibrutinib has been associated with various ophthalmologic side effects, including vision changes and optic neuritis. Therefore, the patient's symptoms may be a side effect of his recent initiation of ibrutinib therapy.\n\nDiagnosis: Ibrutinib-induced optic neuritis.""
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        ""content"": ""The patient's symptoms of bilateral eye pain, decreased vision, and headache, along with the history of Waldenstrom's macroglobulinemia, suggest a neurological complication related to the underlying disease. The CT and MRI findings of thickening and enhancement along the left optic nerve further support this. Waldenstrom's macroglobulinemia can cause hyperviscosity syndrome, which can lead to various neurological symptoms including vision changes. However, the patient's IgM levels are not extremely high, which is typically seen in hyperviscosity syndrome. Another possibility is Bing-Neel syndrome, a rare complication of Waldenstrom's macroglobulinemia where malignant cells infiltrate the central nervous system. This can cause a variety of neurological symptoms, including vision changes and headaches. The patient's recent weight loss and pain with chewing could also be related to this. \n\nDiagnosis: Bing-Neel syndrome.""
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        ""content"": ""The patient is a 65-year-old man presenting with bilateral eye pain, decreased vision, and weight loss. He has a history of Waldenstrom's macroglobulinemia, a type of non-Hodgkin lymphoma that produces an excess of IgM antibodies. The differential diagnosis for this patient includes optic neuritis, glaucoma, uveitis, and central retinal vein occlusion. However, given the patient's history of Waldenstrom's macroglobulinemia and the recent increase in IgM levels, it is also necessary to consider a lymphoma-related cause for his symptoms. The CT and MRI scans show thickening and enhancement along the left optic nerve, which could be due to infiltration by lymphoma cells. The patient's symptoms are not consistent with glaucoma, which typically presents with increased intraocular pressure, and uveitis, which would likely cause more inflammation. Central retinal vein occlusion would typically present with sudden, painless vision loss, which is not consistent with this patient's symptoms. Given the patient's history and the imaging findings, the most likely diagnosis is optic nerve infiltration by Waldenstrom's macroglobulinemia.\n\nDiagnosis: Optic nerve infiltration by Waldenstrom's macroglobulinemia.""
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10.1056/NEJMcpc1913474,Case 5-2021: A 68-Year-Old Man with Delirium and Renal Insufficiency,"Hemoglobin (g/dl) 12.7–16.7 12.3 13.8–17.4 10.6   9.2
Hematocrit (%) 38.1–50.1 36.4   30.7   26.8
White-cell count (per μl) 3800–10,050 2120 440 ,300 3000   2740
Differential count (per μl)
Neutrophils 1187 2790   2512
Lymphocytes 487 60   79
Monocytes 402 90   128
Eosinophils 0 0   0
Immature granulocytes 21 60 0–100 19
Platelet count (per μl)   125,000   92,000   58,000
Sodium (mmol/liter) 134–145 133 134–145 135   142
Potassium (mmol/liter) 3.5–5.1 4.0 3.5–5.1 4.4   3.3
Chloride (mmol/liter) 96–108 98 96–108 96   104
Carbon dioxide (mmol/liter) 22–32 19 22–32 21   22
Urea nitrogen (mg/dl) 8–28 54 8–28 55   47
Creatinine (mg/dl)   3.2   3.4   2.96
Glucose (mg/dl) 7 8 97 7 8 96   89
Phosphorus (mg/dl) 2.3–4.6 4.8 2.3–4.6 4.4   3.2
Calcium (mg/dl)   11.9   9.6   9.8
25-Hydroxyvitamin D (ng/ml)   20   2 0 25
Parathyroid hormone (pg/ml) 15–65 <6 15–65 17             7                                                 Parathyroid hormone–related peptide (pmol/
liter)
0. .3 3.5
1,25-Dihydroxyvitamin D (pg/ml) 19.9–79.3 71.8                                                                 Total protein (g/dl) 6.2–7.9 6.9 6.2–7.9 6.1 6. .3 5.8
Albumin (g/dl) 3.4–5.2 3.9 3.4–5.2 3.6   3.1
Alanine aminotransferase (U/liter) 0–65 68 0–65 34   47
Aspartate aminotransferase (U/liter) 0–43 89 0–43 27   23
Alkaline phosphatase (U/liter) 29–126 259 29–126 104   138
Bone-specific alkaline phosphatase (μg/liter) 6.5–20.1 21.6
Thyrotropin (μIU/ml) 0.27–4.20 8.74 0.30–4.50 2.16 0.4–5.0 5.83
Erythrocyte sedimentation rate (mm/hr)   13   46
Vitamin B12 (pg/ml) 30 000 201 >250 738
C-reactive protein (mg/liter) <5.0 54.4  .0 140.0
Iron (μg/dl) 50–160 66 45–160 13
Total iron-binding capacity (μg/dl) 250–430 178 23 4 159
Ferritin (μg/liter) 41–306 776 2 00 805
Urine
Color Yellow Yellow Yellow Yellow Yellow Yellow
Clarity Clear Slightly cloudy Clear Clear Clear Clear
pH 5.0–7.5 5.0   6.0   5.0
Specific gravity   1.011   1.009   1.009
Glucose Negative Negative Negative Negative Negative Negative
Ketones Negative Negative Negative Negative Negative Negative
Leukocyte esterase Negative Negative Negative Negative Negative +1
Nitrite Negative Negative Negative Negative Negative Negative
Blood Negative Large Negative Negative Negative Negative
Protein Negative 30 mg/dl Negative 30 mg/dl Negative Negative
Red cells (per high-power field)   >100 <2 1    
White cells (per high-power field)   0–5 <4 6   5–10
Bacteria None Rare None Negative None None",Disseminated Mycobacterium bovis infection,Disseminated bacille Calmette–Guérin infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old man was transferred to this hospital because of neurologic decline, progressive renal insufficiency, and leukopenia.
Seven months before this admission, the patient was admitted to another hospital after routine laboratory testing had identified abnormalities, including a creatinine level of 3.2 mg per deciliter (283 mmol per liter; reference range, 0.50 to 1.40 mg per deciliter [44 to 124 mmol per liter]), a blood urea nitrogen level of 54 mg per deciliter (19 mmol per liter; reference range, 7 to 30 mg per deciliter [2.5 to 11 mmol per liter]), and a calcium level of 12.1 mg per deciliter (3.0 mmol per liter; reference range, 8.8 to 10.6 mg per deciliter [2.2 to 2.6 mmol per liter]). Twelve months earlier, the creatinine level had been 1.7 mg per deciliter (150 mmol per liter). On admission to the other hospital, he reported unintentional weight loss of 14 kg over the preceding 12 months, malaise, waking every 2 hours to empty his bladder, and new mild exertional dyspnea. The temperature was 36.6[degrees]C, the heart rate 92 beats per minute, the blood pressure 117/74 mm Hg, and the oxygen saturation 96% while he was breathing ambient air. The weight was 68 kg and the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) 23.5. Examination was notable for cachexia and hepatosplenomegaly (with the liver and spleen palpable 6 cm below the costal margin) without lymphadenopathy. The remainder of the examination was reportedly normal. Blood levels of magnesium, bilirubin, globulin, creatine kinase, uric acid, and N-terminal pro-B-type natriuretic peptide were normal; other laboratory test results are shown in Table 1. Serum protein electrophoresis results were normal; urine protein electrophoresis revealed polyclonal light-chain bands.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Jo-Anne O. Shepard: Computed tomography (CT) of the abdomen and pelvis, performed without the administration of intravenous contrast material, reportedly revealed focal nodular soft-tissue thickening along the aortic arch, descending thoracic aorta, and abdominal aorta. Splenomegaly and left paraaortic adenopathy were present. Small pulmonary nodules and patchy consolidation were observed, along with a small left pleural effusion.
Dr. Matza: After treatment with intravenous normal saline and furosemide, the calcium level normalized and the creatinine level decreased to 2.3 mg per deciliter (203 mmol per liter). The patient was discharged on the fourth hospital day.
Dr. Rory K. Crotty: A bone marrow biopsy performed 2 weeks later at the first hospital revealed hypercellular marrow and multiple nonnecrotizing granulomas. Staining for acid-fast bacilli and fungi was negative. No cultures were obtained.
Dr. Matza: The angiotensin-converting enzyme (ACE) level was 89 U per liter (reference range, 9 to 67). A diagnosis of sarcoidosis was considered, and therapy with high-dose oral prednisone was started.
One month later, the ACE level decreased to 41 U per liter, and the patient's energy level and appetite improved. Attempts to taper the dose of prednisone were unsuccessful owing to increased fatigue and exertional dyspnea.
Three months later, the patient was evaluated by a pulmonologist at the first hospital for pulmonary sarcoidosis. Trimethoprim-sulfamethoxazole was initiated for prophylaxis against pneumocystis while the patient continued to receive high-dose prednisone. Tests of pulmonary function showed mild obstruction, with a clinically significant response after the use of a bronchodilator, and moderate restriction, with moderately reduced diffusing capacity of the lung for carbon monoxide. A second attempt to taper the dose of prednisone was unsuccessful owing to increased fatigue and exertional dyspnea.
During the next 2 months, intermittent confusion, progressive weakness in the legs, right foot drop, and increasing unsteadiness and gait instability developed; the patient began to use a walker to ambulate. He also had at least two falls. He required help from his wife to perform activities of daily living, including bathing and dressing.
The patient was evaluated by a rheumatologist at the first hospital. Complement levels were normal, as was the level of rheumatoid factor. Tests for antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), and anticyclic citrullinated peptide antibodies were negative. Weekly treatment with oral methotrexate and folic acid was started for presumed sarcoidosis.
Eleven days later, the patient presented to a second hospital with a new facial droop on the left side, slurred speech, and confusion. The temperature was 36.4[degrees]C, the heart rate 102 beats per minute, the blood pressure 141/86 mm Hg, and the oxygen saturation 99% while he was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. The weight was 63 kg and the BMI 21.9. The patient was oriented to person, place, and time; neurologic examination was notable for a mild facial droop on the left side, mildly increased muscle tone, right foot drop, and symmetric mild weakness in the arms and upper legs. Cachexia, tachycardia, and splenomegaly were noted. Other laboratory test results are shown in Table 1.
Dr. Pamela W. Schaefer: Magnetic resonance imaging (MRI) of the head revealed a 12-mm right subdural hygroma with a midline shift of 10 mm, a right cerebellar cavernous malformation, and numerous punctate foci (in the pons, left cerebellum, right occipital lobe, and left thalamus) characterized by hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging and restricted diffusion.
Dr. Matza: Clopidogrel and levetiracetam were initiated. Echocardiography did not show intracardiac thrombus or shunting; carotid ultrasonography did not show stenosis. Electromyography revealed evidence of mild L5-S1 radiculopathy and right ulnar and median neuropathy, but there was no evidence of myopathy or upper motor neuron disease. Owing to progressive leukopenia (white-cell count, 1390 per microliter) and thrombocytopenia (platelet count, 51,000 per microliter), methotrexate, clopidogrel, levetiracetam, and trimethoprim-sulfamethoxazole were discontinued; cyanocobalamin was started.
On the fourth hospital day, a fever with a temperature of 38.3[degrees]C developed; specimens of blood and urine were obtained for culture, and intravenous vancomycin and cefepime were initiated. The C-reactive protein level was 101.8 mg per liter. Blood tests for ANA, ANCA, rheumatoid factor, influenza type A and B antigens, human immunodeficiency virus (HIV) type 1 p24 antigen, antibodies to HIV types 1 and 2, hepatitis B virus surface antigen, hepatitis B virus core antibodies, cytomegalovirus DNA, Epstein-Barr virus DNA, and parvovirus IgM were negative, as were urine tests for legionella antigen and histoplasma antigen. A rapid plasma reagin test was negative, and an interferon-[gamma] release assay for the detection of Mycobacterium tuberculosis was reported as indeterminate.
Dr. Shepard: CT of the chest, abdomen, and pelvis, performed without the administration of intravenous contrast material, revealed scattered ground-glass opacities in the lungs, nodular and consolidative opacities in the lungs, mildly enlarged mediastinal lymph nodes, small pleural effusions, and splenomegaly (with the spleen measuring 16 cm in the cephalocaudad dimension; normal length, <13 cm). Focal soft-tissue thickening along the aortic arch and descending thoracic aorta and prominence of the soft tissue surrounding the infrarenal abdominal aorta were also noted.
The next day, magnetic resonance angiography was performed. A T2-weighted fat-saturated image (Figure 1A) showed signal hyperintensity in the soft tissue around the infrarenal aorta and in the adjacent left paraaortic lymph nodes that was indicative of adenopathy, with a focal abdominal aortic pseudoaneurysm seen on time-of-flight imaging (Figure 1B).	
Figure 1
Dr. Matza: On the eighth hospital day, a bone marrow biopsy was performed. On the ninth day, the patient was transferred to this hospital.
On the patient's arrival, a review of systems was limited owing to delirium, and history was obtained in part from the patient's family. The review was notable for months of fatigue, malaise, leg weakness, right foot drop, waxing and waning confusion, exertional dyspnea, and an inability to walk and perform activities of daily living. Palpitations, dry cough, easy bruising, and irritable bladder were present, but he had no chills, anorexia, joint pain, erythema, rashes, nodules, myalgia, chest pain, dizziness, productive cough, hemoptysis, orthopnea, wheezing, gastrointestinal symptoms, dysuria, hematuria, ocular or nasal symptoms, skin or nail changes, or headache.
The patient's medical history was notable for hypothyroidism, hypertension, hypercholesterolemia, progressive kidney disease, degenerative joint disease of the lumbar spine, scoliosis, tubular adenoma, and leukopenia. Eight years before this admission, a mass in the bladder that measured 4.5 cm by 4.0 cm was noted on ultrasonography, which had been performed for evaluation of hematuria. Transurethral resection of the bladder tumor was performed at another hospital, but the resection was reportedly incomplete. Histologic examination revealed non-muscle-invasive papillary urothelial carcinoma. Repeat cystoscopy and transurethral resection, performed 3, 8, and 16 months after the initial procedures, each revealed fragments of non-muscle-invasive papillary urothelial carcinoma, and intravesical bacille Calmette-Guerin (BCG) was administered. Cystoscopy, performed 1 year before this admission for the management of bladder stones, identified a recurrent polypoid bladder tumor, which was treated with transurethral resection.
Outpatient medications included prednisone, methotrexate, folic acid, aspirin, levothyroxine, simvastatin, tamsulosin, cholecalciferol, sodium bicarbonate, calcium carbonate, omeprazole, trimethoprim-sulfamethoxazole, fluticasone-salmeterol, and as-needed inhaled albuterol. Penicillin had caused an unknown reaction.
The patient was a retired pharmacist and lived with his wife. He had a remote history of smoking a half pack of cigarettes daily for 2 years and drank alcohol infrequently. He had not traveled recently and had had no environmental, animal, or toxic exposures. There was no family history of autoimmune, neurologic, infectious, or pulmonary disorders.
The temperature was 36.8[degrees]C, the heart rate 100 beats per minute, the blood pressure 122/76 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 94% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. The weight was 54 kg and the BMI 18.8. He was anxious, cachectic, and appeared chronically ill. He correctly reported his name, location, and the time and date; however, he was unable to follow simple two-step commands. The cranial-nerve examination revealed a subtle facial droop on the left side. There were tremors in the arms and legs at rest and with motion, as well as right foot drop and diffusely increased tone. Finger-nose-finger testing showed dysmetria. Bibasilar crackles (greater in the left lung than in the right) were heard on lung auscultation. Hepatosplenomegaly was present. There were diffuse ecchymoses on the trunk, arms, and legs. The remainder of the examination was normal.
The international normalized ratio and blood levels of ammonia, bilirubin, creatine kinase, folic acid, globulin, haptoglobin, lactate dehydrogenase, lactic acid, and magnesium were normal. The ACE level was 36 U per liter (reference range, 8 to 53). Serum protein electrophoresis showed no bands, but a mild, diffuse decrease in globulin was noted. The urine free kappa light-chain level was 134.2 mg per deciliter (reference range, 0.4 to 15.1), and the urine free lambda light-chain level was 35.6 mg per deciliter (reference range, 0.8 to 10.1), with a normal ratio (3.77; reference range, 0.50 to 4.00). Other laboratory test results are shown in Table 1. Cultures of blood, urine, and sputum were obtained. During the first 3 days of this admission, the patient became lethargic; when he was awakened, his speech was incoherent and dysarthric.
Dr. Schaefer: On the third hospital day, MRI of the head (Figure 2) with magnetic resonance angiography revealed a stable right subdural hygroma with a midline shift of 10 mm, as well as a stable right cerebellar cavernous malformation. There were punctate and patchy foci characterized by hyperintensity on FLAIR imaging and restricted diffusion in the midbrain, pons, medulla, left cerebellum, right occipital lobe, and left thalamus; the foci had increased in size and extent from the previous study.	
Figure 2
Dr. Shepard: Positron-emission tomography (PET)-CT (Figure 1D through 1F) revealed multiple foci of 18F-fluorodeoxyglucose (FDG) uptake in periaortic soft tissue and paraaortic lymph nodes, in the axial skeleton (cervical vertebral body, ribs, manubrium, and sacrum), and in the left testis.
Dr. Matza: Blood tests for alpha-fetoprotein, 1,3-[beta]-d-glucan, coxiella antibodies, cytomegalovirus IgM and IgG, cryptococcal antigen, human chorionic gonadotropin, and Treponema pallidum antibodies were negative, as was a urine test for histoplasma antigen. Electroencephalographic monitoring showed frequent sharp, irregular delta and theta discharges; treatment with levetiracetam was started.
On the fourth hospital day, the temperature was 38.3[degrees]C. Ultrasound images showed testes of normal size and echotexture without focal lesions, but the epididymides were enlarged and heterogeneous. The kidneys were normal in size, with diffusely echogenic parenchyma, and a 19-mm bladder stone was present. A transthoracic echocardiogram showed normal ventricular function, no evidence of clinically significant valvular disease, and a mildly dilated aorta. Flow cytometry showed a markedly reduced CD4+ T-cell count (11 per microliter; reference range, 348 to 1456). Antibody tests for bartonella and brucella were negative.
Somnolence progressed, and on the fifth hospital day, the right pupil was noted to be slightly larger than the left and the patient had increased tremor. Fosphenytoin therapy was initiated, and he was transferred to the neurologic intensive care unit. The oxygen saturation declined to 90% while he was receiving supplemental oxygen through a nasal cannula at a rate of 3 liters per minute, and a Cheyne-Stokes pattern of respiration was observed. The trachea was intubated, and mechanical ventilation was initiated.
A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old man was transferred to this hospital because of neurologic decline, progressive renal insufficiency, and leukopenia.
Seven months before this admission, the patient was admitted to another hospital after routine laboratory testing had identified abnormalities, including a creatinine level of 3.2 mg per deciliter (283 mmol per liter; reference range, 0.50 to 1.40 mg per deciliter [44 to 124 mmol per liter]), a blood urea nitrogen level of 54 mg per deciliter (19 mmol per liter; reference range, 7 to 30 mg per deciliter [2.5 to 11 mmol per liter]), and a calcium level of 12.1 mg per deciliter (3.0 mmol per liter; reference range, 8.8 to 10.6 mg per deciliter [2.2 to 2.6 mmol per liter]). Twelve months earlier, the creatinine level had been 1.7 mg per deciliter (150 mmol per liter). On admission to the other hospital, he reported unintentional weight loss of 14 kg over the preceding 12 months, malaise, waking every 2 hours to empty his bladder, and new mild exertional dyspnea. The temperature was 36.6[degrees]C, the heart rate 92 beats per minute, the blood pressure 117/74 mm Hg, and the oxygen saturation 96% while he was breathing ambient air. The weight was 68 kg and the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) 23.5. Examination was notable for cachexia and hepatosplenomegaly (with the liver and spleen palpable 6 cm below the costal margin) without lymphadenopathy. The remainder of the examination was reportedly normal. Blood levels of magnesium, bilirubin, globulin, creatine kinase, uric acid, and N-terminal pro-B-type natriuretic peptide were normal; other laboratory test results are shown in Table 1. Serum protein electrophoresis results were normal; urine protein electrophoresis revealed polyclonal light-chain bands.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Jo-Anne O. Shepard: Computed tomography (CT) of the abdomen and pelvis, performed without the administration of intravenous contrast material, reportedly revealed focal nodular soft-tissue thickening along the aortic arch, descending thoracic aorta, and abdominal aorta. Splenomegaly and left paraaortic adenopathy were present. Small pulmonary nodules and patchy consolidation were observed, along with a small left pleural effusion.
Dr. Matza: After treatment with intravenous normal saline and furosemide, the calcium level normalized and the creatinine level decreased to 2.3 mg per deciliter (203 mmol per liter). The patient was discharged on the fourth hospital day.
Dr. Rory K. Crotty: A bone marrow biopsy performed 2 weeks later at the first hospital revealed hypercellular marrow and multiple nonnecrotizing granulomas. Staining for acid-fast bacilli and fungi was negative. No cultures were obtained.
Dr. Matza: The angiotensin-converting enzyme (ACE) level was 89 U per liter (reference range, 9 to 67). A diagnosis of sarcoidosis was considered, and therapy with high-dose oral prednisone was started.
One month later, the ACE level decreased to 41 U per liter, and the patient's energy level and appetite improved. Attempts to taper the dose of prednisone were unsuccessful owing to increased fatigue and exertional dyspnea.
Three months later, the patient was evaluated by a pulmonologist at the first hospital for pulmonary sarcoidosis. Trimethoprim-sulfamethoxazole was initiated for prophylaxis against pneumocystis while the patient continued to receive high-dose prednisone. Tests of pulmonary function showed mild obstruction, with a clinically significant response after the use of a bronchodilator, and moderate restriction, with moderately reduced diffusing capacity of the lung for carbon monoxide. A second attempt to taper the dose of prednisone was unsuccessful owing to increased fatigue and exertional dyspnea.
During the next 2 months, intermittent confusion, progressive weakness in the legs, right foot drop, and increasing unsteadiness and gait instability developed; the patient began to use a walker to ambulate. He also had at least two falls. He required help from his wife to perform activities of daily living, including bathing and dressing.
The patient was evaluated by a rheumatologist at the first hospital. Complement levels were normal, as was the level of rheumatoid factor. Tests for antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), and anticyclic citrullinated peptide antibodies were negative. Weekly treatment with oral methotrexate and folic acid was started for presumed sarcoidosis.
Eleven days later, the patient presented to a second hospital with a new facial droop on the left side, slurred speech, and confusion. The temperature was 36.4[degrees]C, the heart rate 102 beats per minute, the blood pressure 141/86 mm Hg, and the oxygen saturation 99% while he was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. The weight was 63 kg and the BMI 21.9. The patient was oriented to person, place, and time; neurologic examination was notable for a mild facial droop on the left side, mildly increased muscle tone, right foot drop, and symmetric mild weakness in the arms and upper legs. Cachexia, tachycardia, and splenomegaly were noted. Other laboratory test results are shown in Table 1.
Dr. Pamela W. Schaefer: Magnetic resonance imaging (MRI) of the head revealed a 12-mm right subdural hygroma with a midline shift of 10 mm, a right cerebellar cavernous malformation, and numerous punctate foci (in the pons, left cerebellum, right occipital lobe, and left thalamus) characterized by hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging and restricted diffusion.
Dr. Matza: Clopidogrel and levetiracetam were initiated. Echocardiography did not show intracardiac thrombus or shunting; carotid ultrasonography did not show stenosis. Electromyography revealed evidence of mild L5-S1 radiculopathy and right ulnar and median neuropathy, but there was no evidence of myopathy or upper motor neuron disease. Owing to progressive leukopenia (white-cell count, 1390 per microliter) and thrombocytopenia (platelet count, 51,000 per microliter), methotrexate, clopidogrel, levetiracetam, and trimethoprim-sulfamethoxazole were discontinued; cyanocobalamin was started.
On the fourth hospital day, a fever with a temperature of 38.3[degrees]C developed; specimens of blood and urine were obtained for culture, and intravenous vancomycin and cefepime were initiated. The C-reactive protein level was 101.8 mg per liter. Blood tests for ANA, ANCA, rheumatoid factor, influenza type A and B antigens, human immunodeficiency virus (HIV) type 1 p24 antigen, antibodies to HIV types 1 and 2, hepatitis B virus surface antigen, hepatitis B virus core antibodies, cytomegalovirus DNA, Epstein-Barr virus DNA, and parvovirus IgM were negative, as were urine tests for legionella antigen and histoplasma antigen. A rapid plasma reagin test was negative, and an interferon-[gamma] release assay for the detection of Mycobacterium tuberculosis was reported as indeterminate.
Dr. Shepard: CT of the chest, abdomen, and pelvis, performed without the administration of intravenous contrast material, revealed scattered ground-glass opacities in the lungs, nodular and consolidative opacities in the lungs, mildly enlarged mediastinal lymph nodes, small pleural effusions, and splenomegaly (with the spleen measuring 16 cm in the cephalocaudad dimension; normal length, <13 cm). Focal soft-tissue thickening along the aortic arch and descending thoracic aorta and prominence of the soft tissue surrounding the infrarenal abdominal aorta were also noted.
The next day, magnetic resonance angiography was performed. A T2-weighted fat-saturated image (Figure 1A) showed signal hyperintensity in the soft tissue around the infrarenal aorta and in the adjacent left paraaortic lymph nodes that was indicative of adenopathy, with a focal abdominal aortic pseudoaneurysm seen on time-of-flight imaging (Figure 1B).	
Figure 1
Dr. Matza: On the eighth hospital day, a bone marrow biopsy was performed. On the ninth day, the patient was transferred to this hospital.
On the patient's arrival, a review of systems was limited owing to delirium, and history was obtained in part from the patient's family. The review was notable for months of fatigue, malaise, leg weakness, right foot drop, waxing and waning confusion, exertional dyspnea, and an inability to walk and perform activities of daily living. Palpitations, dry cough, easy bruising, and irritable bladder were present, but he had no chills, anorexia, joint pain, erythema, rashes, nodules, myalgia, chest pain, dizziness, productive cough, hemoptysis, orthopnea, wheezing, gastrointestinal symptoms, dysuria, hematuria, ocular or nasal symptoms, skin or nail changes, or headache.
The patient's medical history was notable for hypothyroidism, hypertension, hypercholesterolemia, progressive kidney disease, degenerative joint disease of the lumbar spine, scoliosis, tubular adenoma, and leukopenia. Eight years before this admission, a mass in the bladder that measured 4.5 cm by 4.0 cm was noted on ultrasonography, which had been performed for evaluation of hematuria. Transurethral resection of the bladder tumor was performed at another hospital, but the resection was reportedly incomplete. Histologic examination revealed non-muscle-invasive papillary urothelial carcinoma. Repeat cystoscopy and transurethral resection, performed 3, 8, and 16 months after the initial procedures, each revealed fragments of non-muscle-invasive papillary urothelial carcinoma, and intravesical bacille Calmette-Guerin (BCG) was administered. Cystoscopy, performed 1 year before this admission for the management of bladder stones, identified a recurrent polypoid bladder tumor, which was treated with transurethral resection.
Outpatient medications included prednisone, methotrexate, folic acid, aspirin, levothyroxine, simvastatin, tamsulosin, cholecalciferol, sodium bicarbonate, calcium carbonate, omeprazole, trimethoprim-sulfamethoxazole, fluticasone-salmeterol, and as-needed inhaled albuterol. Penicillin had caused an unknown reaction.
The patient was a retired pharmacist and lived with his wife. He had a remote history of smoking a half pack of cigarettes daily for 2 years and drank alcohol infrequently. He had not traveled recently and had had no environmental, animal, or toxic exposures. There was no family history of autoimmune, neurologic, infectious, or pulmonary disorders.
The temperature was 36.8[degrees]C, the heart rate 100 beats per minute, the blood pressure 122/76 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 94% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. The weight was 54 kg and the BMI 18.8. He was anxious, cachectic, and appeared chronically ill. He correctly reported his name, location, and the time and date; however, he was unable to follow simple two-step commands. The cranial-nerve examination revealed a subtle facial droop on the left side. There were tremors in the arms and legs at rest and with motion, as well as right foot drop and diffusely increased tone. Finger-nose-finger testing showed dysmetria. Bibasilar crackles (greater in the left lung than in the right) were heard on lung auscultation. Hepatosplenomegaly was present. There were diffuse ecchymoses on the trunk, arms, and legs. The remainder of the examination was normal.
The international normalized ratio and blood levels of ammonia, bilirubin, creatine kinase, folic acid, globulin, haptoglobin, lactate dehydrogenase, lactic acid, and magnesium were normal. The ACE level was 36 U per liter (reference range, 8 to 53). Serum protein electrophoresis showed no bands, but a mild, diffuse decrease in globulin was noted. The urine free kappa light-chain level was 134.2 mg per deciliter (reference range, 0.4 to 15.1), and the urine free lambda light-chain level was 35.6 mg per deciliter (reference range, 0.8 to 10.1), with a normal ratio (3.77; reference range, 0.50 to 4.00). Other laboratory test results are shown in Table 1. Cultures of blood, urine, and sputum were obtained. During the first 3 days of this admission, the patient became lethargic; when he was awakened, his speech was incoherent and dysarthric.
Dr. Schaefer: On the third hospital day, MRI of the head (Figure 2) with magnetic resonance angiography revealed a stable right subdural hygroma with a midline shift of 10 mm, as well as a stable right cerebellar cavernous malformation. There were punctate and patchy foci characterized by hyperintensity on FLAIR imaging and restricted diffusion in the midbrain, pons, medulla, left cerebellum, right occipital lobe, and left thalamus; the foci had increased in size and extent from the previous study.	
Figure 2
Dr. Shepard: Positron-emission tomography (PET)-CT (Figure 1D through 1F) revealed multiple foci of 18F-fluorodeoxyglucose (FDG) uptake in periaortic soft tissue and paraaortic lymph nodes, in the axial skeleton (cervical vertebral body, ribs, manubrium, and sacrum), and in the left testis.
Dr. Matza: Blood tests for alpha-fetoprotein, 1,3-[beta]-d-glucan, coxiella antibodies, cytomegalovirus IgM and IgG, cryptococcal antigen, human chorionic gonadotropin, and Treponema pallidum antibodies were negative, as was a urine test for histoplasma antigen. Electroencephalographic monitoring showed frequent sharp, irregular delta and theta discharges; treatment with levetiracetam was started.
On the fourth hospital day, the temperature was 38.3[degrees]C. Ultrasound images showed testes of normal size and echotexture without focal lesions, but the epididymides were enlarged and heterogeneous. The kidneys were normal in size, with diffusely echogenic parenchyma, and a 19-mm bladder stone was present. A transthoracic echocardiogram showed normal ventricular function, no evidence of clinically significant valvular disease, and a mildly dilated aorta. Flow cytometry showed a markedly reduced CD4+ T-cell count (11 per microliter; reference range, 348 to 1456). Antibody tests for bartonella and brucella were negative.
Somnolence progressed, and on the fifth hospital day, the right pupil was noted to be slightly larger than the left and the patient had increased tremor. Fosphenytoin therapy was initiated, and he was transferred to the neurologic intensive care unit. The oxygen saturation declined to 90% while he was receiving supplemental oxygen through a nasal cannula at a rate of 3 liters per minute, and a Cheyne-Stokes pattern of respiration was observed. The trachea was intubated, and mechanical ventilation was initiated.
A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms include neurologic decline, progressive renal insufficiency, and leukopenia. He also has a history of unintentional weight loss, malaise, waking every 2 hours to empty his bladder, and new mild exertional dyspnea. His lab results show abnormalities in creatinine and calcium levels. He also has hepatosplenomegaly and cachexia. His bone marrow biopsy revealed hypercellular marrow and multiple nonnecrotizing granulomas. His ACE level was elevated, leading to a consideration of sarcoidosis. However, his symptoms did not improve with prednisone treatment. He also developed intermittent confusion, progressive weakness in the legs, right foot drop, and increasing unsteadiness and gait instability. His MRI revealed a right subdural hygroma with a midline shift of 10 mm, a right cerebellar cavernous malformation, and numerous punctate foci. His PET-CT revealed multiple foci of 18F-fluorodeoxyglucose (FDG) uptake in periaortic soft tissue and paraaortic lymph nodes, in the axial skeleton, and in the left testis. All these findings suggest a systemic disease that affects multiple organs. The presence of non-necrotizing granulomas in the bone marrow, elevated ACE levels, and the FDG uptake in the lymph nodes and axial skeleton are suggestive of sarcoidosis. However, the neurologic symptoms and the findings on the MRI are not typical for sarcoidosis. The presence of FDG uptake in the left testis raises the possibility of testicular lymphoma, which can present with systemic symptoms and can cause neurologic symptoms due to central nervous system involvement. However, the ultrasound of the testes did not show any focal lesions. The presence of a right subdural hygroma and the neurologic symptoms could also suggest a subdural hematoma, but this would not explain the systemic symptoms and the renal insufficiency. The presence of FDG uptake in the periaortic soft tissue and paraaortic lymph nodes could suggest aortitis, but this would not explain the neurologic symptoms and the renal insufficiency. The presence of FDG uptake in the axial skeleton could suggest metastatic cancer, but the bone marrow biopsy did not show any malignant cells. The presence of multiple punctate foci on the MRI could suggest multiple sclerosis, but this would not explain the systemic symptoms and the renal insufficiency. The presence of a right cerebellar cavernous malformation could suggest a vascular malformation, but this would not explain the systemic symptoms and the renal insufficiency. The presence of a right foot drop could suggest a peripheral neuropathy, but this would not explain the systemic symptoms and the renal insufficiency. The presence of cachexia and the unintentional weight loss could suggest a chronic wasting disease such as cancer or AIDS, but the patient's HIV test was negative and the bone marrow biopsy did not show any malignant cells. The presence of hepatosplenomegaly could suggest a liver disease such as cirrhosis or a blood disease such as leukemia, but the patient's liver function tests were normal and the bone marrow biopsy did not show any malignant cells. The presence of an elevated creatinine level and a history of progressive kidney disease could suggest a kidney disease such as chronic kidney disease or glomerulonephritis, but the patient's urine tests did not show any signs of kidney damage. The presence of an elevated calcium level could suggest a parathyroid disease such as hyperparathyroidism, but the patient's parathyroid hormone level was not reported. The presence of a low white blood cell count could suggest a bone marrow disease such as aplastic anemia or leukemia, but the bone marrow biopsy did not show any signs of these diseases. The presence of a low platelet count could suggest a blood disease such as thrombocytopenia or a liver disease such as cirrhosis, but the patient's liver function tests were normal and the bone marrow biopsy did not show any signs of these diseases. The presence of a high ACE level could suggest a lung disease such as sarcoidosis or a kidney disease such as renal artery stenosis, but the patient's lung function tests were normal and his kidney function tests showed renal insufficiency. The presence of a high C-reactive protein level could suggest an inflammatory disease such as rheumatoid arthritis or a bacterial infection, but the patient's rheumatoid factor level was normal and his blood cultures were negative. The presence of a high N-terminal pro-B-type natriuretic peptide level could suggest a heart disease such as heart failure or a kidney disease such as chronic kidney disease, but the patient's echocardiogram was normal and his kidney function tests showed renal insufficiency. The presence of a high uric acid level could suggest a metabolic disease such""
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        ""content"": ""The patient's symptoms include neurologic decline, progressive renal insufficiency, and leukopenia. He also has a history of unintentional weight loss, malaise, waking every 2 hours to empty his bladder, and new mild exertional dyspnea. His lab results show abnormalities in creatinine and calcium levels. He also has hepatosplenomegaly and cachexia. His symptoms and lab results suggest a systemic disease. The presence of nonnecrotizing granulomas in the bone marrow biopsy and elevated ACE levels suggest sarcoidosis. However, the patient's condition did not improve with prednisone treatment, which is typically effective for sarcoidosis. The patient also developed new symptoms including confusion, progressive weakness in the legs, right foot drop, and increasing unsteadiness and gait instability. His lab results also show leukopenia and thrombocytopenia. The presence of multiple foci of FDG uptake in periaortic soft tissue and paraaortic lymph nodes, in the axial skeleton, and in the left testis on PET-CT suggest malignancy. The patient's symptoms, lab results, and imaging findings are consistent with Erdheim-Chester disease, a rare form of non-Langerhans cell histiocytosis.\n\nDiagnosis: Erdheim-Chester disease.""
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        ""content"": ""The patient is a 68-year-old man with a history of bladder cancer who presents with neurologic decline, progressive renal insufficiency, and leukopenia. His symptoms include unintentional weight loss, malaise, nocturia, mild exertional dyspnea, cachexia, hepatosplenomegaly, and hypercalcemia. His condition has been progressively worsening over the past seven months. The differential diagnosis for this patient includes sarcoidosis, lymphoma, multiple myeloma, and systemic lupus erythematosus (SLE). \n\nSarcoidosis was initially considered due to the presence of nonnecrotizing granulomas in the bone marrow and elevated ACE levels. However, the patient's symptoms did not improve with high-dose prednisone, which is typically effective in treating sarcoidosis. \n\nLymphoma could explain the patient's symptoms, including weight loss, malaise, hepatosplenomegaly, and hypercalcemia. However, the patient's bone marrow biopsy did not show any malignant cells, making this diagnosis less likely. \n\nMultiple myeloma could also explain the patient's symptoms, including renal insufficiency, hypercalcemia, and bone pain. However, the patient's serum and urine protein electrophoresis did not show any monoclonal proteins, which are typically present in multiple myeloma. \n\nSLE could explain the patient's symptoms, including fatigue, weight loss, and renal insufficiency. However, the patient's ANA and anti-dsDNA tests were negative, making this diagnosis less likely. \n\nGiven the patient's symptoms, the presence of nonnecrotizing granulomas in the bone marrow, the elevated ACE levels, and the lack of response to high-dose prednisone, the most likely diagnosis is sarcoidosis. However, the patient's symptoms and laboratory findings are also consistent with Erdheim-Chester disease, a rare form of non-Langerhans cell histiocytosis. This disease is characterized by the infiltration of tissues with lipid-laden macrophages, multinucleated giant cells, and inflammatory infiltrates. It can affect multiple organ systems, including the skeletal, cardiovascular, and central nervous systems. \n\nDiagnosis: Erdheim-Chester disease.""
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}",Erdheim-Chester disease,N
10.1056/NEJMcpc2027088,Case 4-2021: A 70-Year-Old Woman with Dyspnea on Exertion and Abnormal Findings on Chest Imaging,"FEV1
Value (liters) 1.69 1.41 1.30 1.48 1.41 1.56 1.05 1.37 1.30 1.31
% of predicted value 60 55 51 57 50 55 54 51 57                                                                                                                                          FVC
Value (liters) 2.11 2.13 2.32 2.48 2.08 2.50 1.67 2.01 1.93 1.99
% of predicted value 60 66 73 76 56 68 65 57 66
Ratio of FEV1 to FVC 0.80 0.66 0.56 0.60 0.68 0.62 0.63 0.68 0.67 0.66
Total lung capacity
Value (liters) 4.30 5.02 4.34 4.56 4.81
% of predicted value 79 69 77 81 86
Residual volume
Value (liters) 1.80 2.52 2.33 2.41 2.71
% of predicted value 85 110 104 104
DLco corrected for hemo‚Äë
globin
Value (ml/min/mm Hg) 17.9 18.31 15.22 14.41 13.75
% of predicted value 71 75 64 66 63
Bronchodilator testing† FEV1, 1.40 liters No response FEV1, 1.58 liters No response","Diffuse idiopathic pulmonary neuroendocrine 
cell hyperplasia.",Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old woman was evaluated at the pulmonary clinic of this hospital because of increasing dyspnea on exertion and abnormal findings on chest imaging.
In childhood, the patient had eczema, recurrent episodes of bronchitis with a cough productive of mucus, and allergic rhinitis; these conditions abated in adulthood. Twenty years before this evaluation, she had community-acquired pneumonia. Fifteen years before this evaluation, she had an inhalation exposure to aerosolized brick and mortar at a construction site near her home; she subsequently had bronchitis that was treated with a course of nebulizers and inhaled glucocorticoids.
Twelve years before this evaluation, the patient began to have episodes of coryza, nasal congestion, itchy and watery eyes, and wheezing, especially in the spring or with exposure to cats, dogs, or dust. She was seen by an allergist. Skin-prick testing elicited a response to dust mites, and intradermal testing elicited a response to tree mix and dog dander. Results of pulmonary-function tests are shown in Table 1. Presumptive diagnoses of asthma and seasonal and environmental allergies were made. She received prescriptions for fexofenadine, mometasone, and inhaled albuterol, to be taken as needed.	
Table 1 
Eleven years before this evaluation, computed tomography (CT) of the abdomen incidentally revealed mild mosaic attenuation - a patchy ground-glass pattern - at the lung bases. Ten years before this evaluation, the patient was seen by her primary care physician because of several weeks of nonproductive cough, nasal congestion, and intermittent wheezing; she received prescriptions for oral loratadine and inhaled pirbuterol, to be taken as needed. Eight years before this evaluation, she was referred to an allergist. She was considered to have a cough in response to angiotensin-converting-enzyme inhibitors. Six years 3 months before this evaluation, she consulted with another allergist. Results of pulmonary-function tests are shown in Table 1. The blood IgE level was 1532 kU per liter (reference range at other institution, <127), with positive titers in response to cat dander, dog dander, and dust mites. Inhaled fluticasone was prescribed. Three months later, she had mild dyspnea on exertion and occasional wheezing. Pulmonary-function tests showed minimal change (Table 1); inhaled fluticasone-salmeterol was prescribed.
Five years 9 months before this evaluation, the patient was referred for pulmonary consultation. She reported intermittent wheezing, mild exertional dyspnea after climbing two flights of stairs or carrying groceries, occasional gastroesophageal reflux, and snoring. The heart rate was 72 beats per minute, and the oxygen saturation 95% while she was breathing ambient air at rest. Examination revealed upper-airway wheezing and was otherwise normal. After the patient climbed four flights of stairs, the heart rate was 102 beats per minute, and the oxygen saturation 91% while she was breathing ambient air. Results of pulmonary-function tests are shown in Table 1. A chest radiograph was reportedly normal. Blood levels of electrolytes, urea nitrogen, creatinine, and hemoglobin were normal, as was the platelet count; the white-cell count was 11,900 per microliter (reference range, 4500 to 11,000) and the eosinophil count was 390 per microliter (reference range, <600), with a relative eosinophil count of 3.2% (reference range, 0 to 3). Antinuclear antibody (ANA) and antineutrophil cytoplasmic antibody (ANCA) levels were undetectable.
Dr. Amita Sharma: Chest CT, performed without the administration of contrast material, revealed bilateral mosaic attenuation, as well as several lung nodules measuring 2 to 4 mm in diameter. There was no evidence of bronchiectasis.
Dr. Medoff: The patient was seen by an otolaryngologist. External and fiberoptic examinations, including examination of the vocal cords, were normal. A sleep study revealed mild sleep apnea, with an apnea-hypopnea index of 7.2 events per hour (reference range, <5). The patient was unable to receive supplemental oxygen at night and positive-pressure ventilation owing to side effects.
Five years before this evaluation, the patient underwent cardiac evaluation because of ongoing dyspnea on exertion. A transthoracic echocardiogram was normal. Results of an exercise stress test (treadmill test) were submaximal, with a maximum heart rate at 74% of the age-predicted value but without abnormal findings on electrocardiography. Results of pulmonary-function tests are shown in Table 1. Three months later, the patient attended follow-up with her pulmonologist; inhaled budesonide-formoterol was substituted for inhaled fluticasone-salmeterol, and weight loss was advised.
Dr. Sharma: Four years before this evaluation, repeat chest CT, performed without the administration of contrast material, revealed bilateral mosaic attenuation and multiple bilateral lung nodules measuring 2 to 4 mm in diameter. All the findings were stable from the previous CT scan.
Dr. Medoff: The patient was seen by a second pulmonologist, and inhaled budesonide was substituted for inhaled budesonide-formoterol for the treatment of mild intermittent asthma. Results of pulmonary-function tests obtained 4 years before this evaluation are shown in Table 1. Subsequently, the patient was evaluated annually by her first pulmonologist, but after 3 years, she consulted with a third pulmonologist regarding recurrent dyspnea on exertion. Results of pulmonary-function tests obtained 7 months before this evaluation are shown in Table 1.
Dr. Sharma: At that time, chest CT, performed after the administration of intravenous contrast material, revealed bilateral mosaic attenuation and a nodule measuring 6 mm in diameter in the posterior right upper lobe, along with other, diffuse lung nodules measuring 2 to 4 mm in diameter.
Dr. Medoff: The blood hemoglobin level, platelet count, and white-cell count were normal; the eosinophil count was 437 per microliter, with a relative eosinophil count of 4.9%. The ANA titer was 1:1280, with a homogeneous staining pattern. The IgE level was 2685 kU per liter (reference range at other institution, <114), with positive titers in response to cat dander, dog dander, dust mites, and Cladosporium herbarum. Treatment with oral montelukast and inhaled fluticasone-umeclidinium-vilanterol was started, along with supplemental oxygen to be used at night and with exertion. After 1 month, the patient's symptoms had not abated, and subcutaneous benralizumab was prescribed.
Three months before this evaluation, the patient's symptoms remained unchanged. Results of pulmonary-function tests are shown in Table 1. One month later, 18F-fluorodeoxyglucose (FDG)-positron-emission tomography and CT revealed no areas of abnormal FDG avidity in the lungs. Eight weeks later, the patient was referred to the pulmonary clinic of this hospital.
The patient reported intermittent wheezing and progressive mild exertional dyspnea after climbing one to two flights of stairs. She had stopped playing a team aerobic sport because of difficulty breathing. The symptoms did not abate with use of the inhaler or benralizumab; they never occurred at rest. She occasionally had a nonproductive cough without hemoptysis, and she had a ""raspy"" voice that had become worse in recent months. Coryza, nasal congestion, and watery eyes were not present. She had gained 15 kg during the previous 5 years.
The patient's medical history included eczema, hypothyroidism, obesity, dyslipidemia, hypertension, borderline diabetes, calcium oxalate nephrolithiasis, glaucoma, and colonic polyps. She had undergone tonsillectomy and multiple procedures for the treatment of nephrolithiasis, including shock-wave lithotripsy and ureteroscopy.
Medications included oral aspirin, amlodipine, atenolol, atorvastatin, atovaquone, levothyroxine, loratadine, losartan, and montelukast, along with a multivitamin; inhaled fluticasone-umeclidinium-vilanterol; and subcutaneous benralizumab. Sulfa drugs had caused anaphylaxis, lisinopril had caused a cough, and macrolides had caused diarrhea.
The patient worked as an educator. She had no known exposure to asbestos, mold, solvents, or chemicals. She was a lifelong nonsmoker and did not have secondhand exposure to tobacco; she drank one glass of wine per week and did not use illicit drugs. She had traveled to coastal areas of Florida and Massachusetts, as well as other areas of New England, but she had not traveled to other areas of the United States or outside the country. The patient was married and lived in Massachusetts with her spouse. There had been no pets in her home for approximately 10 years. There were no damp areas in her home; she used a vacuum cleaner with a high-efficiency particulate air (HEPA) filter and allergen-proof bedsheets.
The patient's family history was notable for coronary artery and peripheral artery disease in her father, a sister, and her brother; skin cancer in her mother; breast cancer in a sister; and hypertension and diabetes in multiple relatives. She had two healthy adult children. There was no history of allergic, immunologic, pulmonary, or rheumatologic disease.
The temperature was 36.6[degrees]C, the heart rate 67 beats per minute, the blood pressure 142/91 mm Hg, and the oxygen saturation 92% while the patient was breathing ambient air. After she climbed two flights of stairs, the oxygen saturation was 87% while she was breathing ambient air. She had a cushingoid appearance. The nasal and oral mucosa appeared normal. There was no tracheal deviation or stridor. Lung auscultation revealed normal breath sounds. There was no clubbing or edema. Mild scattered eczematous plaques were present on the forearms and shins. There were mild Heberden's nodes but no other joint, skin, or nail abnormalities. The remainder of the examination was normal.
The blood hemoglobin level, white-cell count, differential count (with 0% eosinophils), platelet count, erythrocyte sedimentation rate, and creatine kinase level were normal. The IgE level was 1307 IU per milliliter (reference range at this hospital, 0 to 100), and a hypersensitivity pneumonitis panel was negative. The thyrotropin level was 8.07 [mu]IU per milliliter (reference range, 0.40 to 5.00), and the aldolase level 9.3 U per liter (reference range, <7.7). The ANA titer was 1:5120, with a homogeneous and speckled staining pattern; the anticytoplasmic antibody titer was 1:1280, with a filamentous and granular staining pattern; and ANCA testing was negative. A transthoracic echocardiogram was normal.
Ten weeks after evaluation, at follow-up in the pulmonary clinic, a myositis antibody panel was negative, except for a weakly positive titer in response to anti-Ku antibodies. Tests were negative for ANCA, anti-cyclic citrullinated peptide, rheumatoid factor, and anti-double-stranded DNA, anti-Ro, anti-La, anti-Smith, antiribonucleoprotein, antitopoisomerase I (anti-Scl-70), antimitochondrial, antithyroperoxidase, and anti-histidyl-transfer RNA synthase (anti-Jo-1) antibodies.
Dr. Sharma: Chest CT (Figure 1A and 1B), performed without the administration of contrast material, revealed diffuse bilateral mosaic attenuation and multiple bilateral lung nodules, including a 6-mm nodule in the right upper lobe. There was no evidence of pulmonary fibrosis, bronchiectasis, or lymphadenopathy.	
Figure 1 
Dr. Medoff: Five days later, the patient was evaluated by a rheumatologist at this hospital. A tapering course of oral prednisone was prescribed for the treatment of possible interstitial pneumonia with autoimmune features.
Ten weeks after the visit with the rheumatologist, the eczematous rash had improved but dyspnea on exertion persisted during long walks. An examination in the pulmonary clinic was notable for clear lung fields and an oxygen saturation of 95% while the patient was breathing ambient air. Results of pulmonary-function tests are shown in Table 1.
Dr. Sharma: Chest CT, performed without the administration of contrast material, again showed extensive bilateral mosaic attenuation and numerous bilateral solid lung nodules, with the largest nodule, measuring 6 mm in diameter, located in the right upper lobe. There was no evidence of bronchiectasis or reticulation. Expiratory CT (Figure 1C and 1D) confirmed the presence of air trapping.
Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old woman was evaluated at the pulmonary clinic of this hospital because of increasing dyspnea on exertion and abnormal findings on chest imaging.
In childhood, the patient had eczema, recurrent episodes of bronchitis with a cough productive of mucus, and allergic rhinitis; these conditions abated in adulthood. Twenty years before this evaluation, she had community-acquired pneumonia. Fifteen years before this evaluation, she had an inhalation exposure to aerosolized brick and mortar at a construction site near her home; she subsequently had bronchitis that was treated with a course of nebulizers and inhaled glucocorticoids.
Twelve years before this evaluation, the patient began to have episodes of coryza, nasal congestion, itchy and watery eyes, and wheezing, especially in the spring or with exposure to cats, dogs, or dust. She was seen by an allergist. Skin-prick testing elicited a response to dust mites, and intradermal testing elicited a response to tree mix and dog dander. Results of pulmonary-function tests are shown in Table 1. Presumptive diagnoses of asthma and seasonal and environmental allergies were made. She received prescriptions for fexofenadine, mometasone, and inhaled albuterol, to be taken as needed.	
Table 1 
Eleven years before this evaluation, computed tomography (CT) of the abdomen incidentally revealed mild mosaic attenuation - a patchy ground-glass pattern - at the lung bases. Ten years before this evaluation, the patient was seen by her primary care physician because of several weeks of nonproductive cough, nasal congestion, and intermittent wheezing; she received prescriptions for oral loratadine and inhaled pirbuterol, to be taken as needed. Eight years before this evaluation, she was referred to an allergist. She was considered to have a cough in response to angiotensin-converting-enzyme inhibitors. Six years 3 months before this evaluation, she consulted with another allergist. Results of pulmonary-function tests are shown in Table 1. The blood IgE level was 1532 kU per liter (reference range at other institution, <127), with positive titers in response to cat dander, dog dander, and dust mites. Inhaled fluticasone was prescribed. Three months later, she had mild dyspnea on exertion and occasional wheezing. Pulmonary-function tests showed minimal change (Table 1); inhaled fluticasone-salmeterol was prescribed.
Five years 9 months before this evaluation, the patient was referred for pulmonary consultation. She reported intermittent wheezing, mild exertional dyspnea after climbing two flights of stairs or carrying groceries, occasional gastroesophageal reflux, and snoring. The heart rate was 72 beats per minute, and the oxygen saturation 95% while she was breathing ambient air at rest. Examination revealed upper-airway wheezing and was otherwise normal. After the patient climbed four flights of stairs, the heart rate was 102 beats per minute, and the oxygen saturation 91% while she was breathing ambient air. Results of pulmonary-function tests are shown in Table 1. A chest radiograph was reportedly normal. Blood levels of electrolytes, urea nitrogen, creatinine, and hemoglobin were normal, as was the platelet count; the white-cell count was 11,900 per microliter (reference range, 4500 to 11,000) and the eosinophil count was 390 per microliter (reference range, <600), with a relative eosinophil count of 3.2% (reference range, 0 to 3). Antinuclear antibody (ANA) and antineutrophil cytoplasmic antibody (ANCA) levels were undetectable.
Dr. Amita Sharma: Chest CT, performed without the administration of contrast material, revealed bilateral mosaic attenuation, as well as several lung nodules measuring 2 to 4 mm in diameter. There was no evidence of bronchiectasis.
Dr. Medoff: The patient was seen by an otolaryngologist. External and fiberoptic examinations, including examination of the vocal cords, were normal. A sleep study revealed mild sleep apnea, with an apnea-hypopnea index of 7.2 events per hour (reference range, <5). The patient was unable to receive supplemental oxygen at night and positive-pressure ventilation owing to side effects.
Five years before this evaluation, the patient underwent cardiac evaluation because of ongoing dyspnea on exertion. A transthoracic echocardiogram was normal. Results of an exercise stress test (treadmill test) were submaximal, with a maximum heart rate at 74% of the age-predicted value but without abnormal findings on electrocardiography. Results of pulmonary-function tests are shown in Table 1. Three months later, the patient attended follow-up with her pulmonologist; inhaled budesonide-formoterol was substituted for inhaled fluticasone-salmeterol, and weight loss was advised.
Dr. Sharma: Four years before this evaluation, repeat chest CT, performed without the administration of contrast material, revealed bilateral mosaic attenuation and multiple bilateral lung nodules measuring 2 to 4 mm in diameter. All the findings were stable from the previous CT scan.
Dr. Medoff: The patient was seen by a second pulmonologist, and inhaled budesonide was substituted for inhaled budesonide-formoterol for the treatment of mild intermittent asthma. Results of pulmonary-function tests obtained 4 years before this evaluation are shown in Table 1. Subsequently, the patient was evaluated annually by her first pulmonologist, but after 3 years, she consulted with a third pulmonologist regarding recurrent dyspnea on exertion. Results of pulmonary-function tests obtained 7 months before this evaluation are shown in Table 1.
Dr. Sharma: At that time, chest CT, performed after the administration of intravenous contrast material, revealed bilateral mosaic attenuation and a nodule measuring 6 mm in diameter in the posterior right upper lobe, along with other, diffuse lung nodules measuring 2 to 4 mm in diameter.
Dr. Medoff: The blood hemoglobin level, platelet count, and white-cell count were normal; the eosinophil count was 437 per microliter, with a relative eosinophil count of 4.9%. The ANA titer was 1:1280, with a homogeneous staining pattern. The IgE level was 2685 kU per liter (reference range at other institution, <114), with positive titers in response to cat dander, dog dander, dust mites, and Cladosporium herbarum. Treatment with oral montelukast and inhaled fluticasone-umeclidinium-vilanterol was started, along with supplemental oxygen to be used at night and with exertion. After 1 month, the patient's symptoms had not abated, and subcutaneous benralizumab was prescribed.
Three months before this evaluation, the patient's symptoms remained unchanged. Results of pulmonary-function tests are shown in Table 1. One month later, 18F-fluorodeoxyglucose (FDG)-positron-emission tomography and CT revealed no areas of abnormal FDG avidity in the lungs. Eight weeks later, the patient was referred to the pulmonary clinic of this hospital.
The patient reported intermittent wheezing and progressive mild exertional dyspnea after climbing one to two flights of stairs. She had stopped playing a team aerobic sport because of difficulty breathing. The symptoms did not abate with use of the inhaler or benralizumab; they never occurred at rest. She occasionally had a nonproductive cough without hemoptysis, and she had a ""raspy"" voice that had become worse in recent months. Coryza, nasal congestion, and watery eyes were not present. She had gained 15 kg during the previous 5 years.
The patient's medical history included eczema, hypothyroidism, obesity, dyslipidemia, hypertension, borderline diabetes, calcium oxalate nephrolithiasis, glaucoma, and colonic polyps. She had undergone tonsillectomy and multiple procedures for the treatment of nephrolithiasis, including shock-wave lithotripsy and ureteroscopy.
Medications included oral aspirin, amlodipine, atenolol, atorvastatin, atovaquone, levothyroxine, loratadine, losartan, and montelukast, along with a multivitamin; inhaled fluticasone-umeclidinium-vilanterol; and subcutaneous benralizumab. Sulfa drugs had caused anaphylaxis, lisinopril had caused a cough, and macrolides had caused diarrhea.
The patient worked as an educator. She had no known exposure to asbestos, mold, solvents, or chemicals. She was a lifelong nonsmoker and did not have secondhand exposure to tobacco; she drank one glass of wine per week and did not use illicit drugs. She had traveled to coastal areas of Florida and Massachusetts, as well as other areas of New England, but she had not traveled to other areas of the United States or outside the country. The patient was married and lived in Massachusetts with her spouse. There had been no pets in her home for approximately 10 years. There were no damp areas in her home; she used a vacuum cleaner with a high-efficiency particulate air (HEPA) filter and allergen-proof bedsheets.
The patient's family history was notable for coronary artery and peripheral artery disease in her father, a sister, and her brother; skin cancer in her mother; breast cancer in a sister; and hypertension and diabetes in multiple relatives. She had two healthy adult children. There was no history of allergic, immunologic, pulmonary, or rheumatologic disease.
The temperature was 36.6[degrees]C, the heart rate 67 beats per minute, the blood pressure 142/91 mm Hg, and the oxygen saturation 92% while the patient was breathing ambient air. After she climbed two flights of stairs, the oxygen saturation was 87% while she was breathing ambient air. She had a cushingoid appearance. The nasal and oral mucosa appeared normal. There was no tracheal deviation or stridor. Lung auscultation revealed normal breath sounds. There was no clubbing or edema. Mild scattered eczematous plaques were present on the forearms and shins. There were mild Heberden's nodes but no other joint, skin, or nail abnormalities. The remainder of the examination was normal.
The blood hemoglobin level, white-cell count, differential count (with 0% eosinophils), platelet count, erythrocyte sedimentation rate, and creatine kinase level were normal. The IgE level was 1307 IU per milliliter (reference range at this hospital, 0 to 100), and a hypersensitivity pneumonitis panel was negative. The thyrotropin level was 8.07 [mu]IU per milliliter (reference range, 0.40 to 5.00), and the aldolase level 9.3 U per liter (reference range, <7.7). The ANA titer was 1:5120, with a homogeneous and speckled staining pattern; the anticytoplasmic antibody titer was 1:1280, with a filamentous and granular staining pattern; and ANCA testing was negative. A transthoracic echocardiogram was normal.
Ten weeks after evaluation, at follow-up in the pulmonary clinic, a myositis antibody panel was negative, except for a weakly positive titer in response to anti-Ku antibodies. Tests were negative for ANCA, anti-cyclic citrullinated peptide, rheumatoid factor, and anti-double-stranded DNA, anti-Ro, anti-La, anti-Smith, antiribonucleoprotein, antitopoisomerase I (anti-Scl-70), antimitochondrial, antithyroperoxidase, and anti-histidyl-transfer RNA synthase (anti-Jo-1) antibodies.
Dr. Sharma: Chest CT (Figure 1A and 1B), performed without the administration of contrast material, revealed diffuse bilateral mosaic attenuation and multiple bilateral lung nodules, including a 6-mm nodule in the right upper lobe. There was no evidence of pulmonary fibrosis, bronchiectasis, or lymphadenopathy.	
Figure 1 
Dr. Medoff: Five days later, the patient was evaluated by a rheumatologist at this hospital. A tapering course of oral prednisone was prescribed for the treatment of possible interstitial pneumonia with autoimmune features.
Ten weeks after the visit with the rheumatologist, the eczematous rash had improved but dyspnea on exertion persisted during long walks. An examination in the pulmonary clinic was notable for clear lung fields and an oxygen saturation of 95% while the patient was breathing ambient air. Results of pulmonary-function tests are shown in Table 1.
Dr. Sharma: Chest CT, performed without the administration of contrast material, again showed extensive bilateral mosaic attenuation and numerous bilateral solid lung nodules, with the largest nodule, measuring 6 mm in diameter, located in the right upper lobe. There was no evidence of bronchiectasis or reticulation. Expiratory CT (Figure 1C and 1D) confirmed the presence of air trapping.
Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Hypersensitivity Pneumonitis. The patient's history of recurrent bronchitis, eczema, and allergic rhinitis, along with her elevated IgE levels and positive skin-prick and intradermal tests, suggest an allergic or hypersensitivity reaction. Her symptoms of dyspnea on exertion and wheezing, along with the findings of mosaic attenuation and multiple lung nodules on CT, are consistent with hypersensitivity pneumonitis, a condition caused by inhalation of allergens that leads to inflammation and damage in the lungs. The patient's lack of response to asthma and allergy treatments, as well as the absence of bronchiectasis or reticulation on CT, further support this diagnosis.""
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        ""content"": ""The patient's history of eczema, recurrent bronchitis, and allergic rhinitis, along with her positive response to skin-prick testing for dust mites, tree mix, and dog dander, suggest a history of atopy. Her symptoms of dyspnea on exertion, wheezing, and cough, along with the findings of mosaic attenuation and multiple lung nodules on CT, suggest a pulmonary condition. The patient's elevated IgE levels and eosinophil count, along with her positive response to allergens, suggest an allergic or hypersensitivity reaction. The persistence of her symptoms despite treatment with various inhaled corticosteroids and bronchodilators, as well as the lack of improvement with oral prednisone, suggest a non-asthmatic condition. The presence of air trapping on expiratory CT is a characteristic finding in bronchiolitis. Given the patient's history of atopy, the most likely diagnosis is allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity reaction to Aspergillus species that primarily affects patients with asthma or cystic fibrosis. However, the patient's negative hypersensitivity pneumonitis panel and lack of improvement with corticosteroid treatment argue against this diagnosis. The patient's history of exposure to aerosolized brick and mortar, along with her persistent pulmonary symptoms and CT findings, raise the possibility of hypersensitivity pneumonitis, an allergic reaction to inhaled organic dusts. However, the patient's negative hypersensitivity pneumonitis panel argues against this diagnosis. Given the patient's history of atopy, her persistent pulmonary symptoms, the presence of multiple lung nodules on CT, and the lack of a clear alternative diagnosis, the most likely diagnosis is allergic bronchopulmonary aspergillosis (ABPA).\n\nDiagnosis: Allergic Bronchopulmonary Aspergillosis (ABPA)""
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        ""content"": ""The patient is a 70-year-old woman with a history of eczema, recurrent bronchitis, allergic rhinitis, and asthma. She presents with increasing dyspnea on exertion and abnormal findings on chest imaging. The differential diagnosis for this patient includes chronic obstructive pulmonary disease (COPD), asthma, interstitial lung disease, and hypersensitivity pneumonitis. The patient's history of recurrent bronchitis and asthma, along with her symptoms of wheezing and dyspnea on exertion, could suggest COPD or asthma. However, her pulmonary function tests do not show the typical obstructive pattern seen in these conditions. Interstitial lung disease could also present with dyspnea and abnormal chest imaging, but the patient's CT scans do not show the typical fibrotic changes seen in this condition. Hypersensitivity pneumonitis could also be a possibility given the patient's history of allergies and her exposure to aerosolized brick and mortar. However, her hypersensitivity pneumonitis panel was negative. The patient's chest CT scans show bilateral mosaic attenuation and multiple bilateral lung nodules, which are characteristic of a rare lung disease called pulmonary Langerhans cell histiocytosis (PLCH). This condition is often seen in smokers, but can also occur in non-smokers. The patient's history of eczema, a condition that involves overactive immune cells, could potentially predispose her to PLCH, which is caused by an overproduction of immune cells in the lungs. \n\nDiagnosis: Pulmonary Langerhans cell histiocytosis (PLCH)""
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10.1056/NEJMcpc2002416,Case 3-2021: A 48-Year-Old Man with Transient Vision Loss,"White-cell count (per μl)   6310
Differential count (per μl)
Neutrophils   4520
Lymphocytes   1160
Monocytes   440
Eosinophils   170
Basophils  00 20
Hemoglobin (g/dl)   11.6
Hematocrit (%)   35.0
Platelet count (per μl)   258,000
Erythrocyte sedimentation rate (mm/hr)   53
C-reactive protein (mg/liter)  .0 11.8
Alanine aminotransferase (U/liter)   245
Aspartate aminotransferase (U/liter)   154
Alkaline phosphatase (U/liter)   1924
Bilirubin (mg/dl)
Total  2.8
Direct  0.0
Protein (g/dl)
Total 6. .3 7.6
Albumin   4.2
Globulin   3.4
Cholesterol (mg/dl)
Total <200 280
Low-density lipoprotein   168",Systemic primary amyloidosis,Systemic primary amyloidosis,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old man was evaluated at this hospital because of transient vision loss.
The patient had been in his usual state of good health until 1 hour before evaluation, when he noticed white ""sparkles"" flickering in the vision of the left eye, followed by sudden blurriness. He had no floaters or eye pain. During the next 2 minutes, the blurry vision worsened and became ""dark,"" such that the patient could not see a hand in front of his face when he covered the right eye. He presented to this hospital for evaluation, arriving 1 hour after the onset of vision symptoms.
On presentation, the patient noted that the vision in the left eye was improving but remained blurry. The temperature was 36.7[degrees]C, the blood pressure 120/65 mm Hg, the heart rate 92 beats per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.2. Visual acuity was 20/20 in the right eye and was limited to hand motions at 0.9 m (3.0 ft) in the left eye; 2 hours later, visual acuity in the left eye was 20/40 for distance vision and 20/30 with correction for near vision. Results of the Ishihara color test were normal. The pupils were equal, round, and reactive to light, with no relative afferent pupillary defect. Extraocular movements were intact; visual fields were full in response to confrontation. Intraocular pressure and results of a slit-lamp examination of the anterior and posterior segments of the eye were normal bilaterally. There was severe ptosis of the left upper eyelid (margin reflex distance, 4 mm in the right eye and 1 mm in the left eye). A dilated fundus examination revealed normal optic disks, maculae, and vessels. A nontender, irregular mass was palpable under the left superior orbital rim, but there was no proptosis. The temporal arteries were prominent bilaterally, more so on the right side than on the left side, with normal pulsations and no tenderness. There was no tenderness of the scalp or temporomandibular joints. The remainder of the physical examination was normal.
A review of systems was notable for fatigue and weight loss of 4.5 kg in the past year, which the patient attributed to inactivity and decreased appetite. There was a 2-month history of bilateral jaw pain with chewing of firm foods but not with soft foods. There was lateral hip soreness in both hips after walking but no stiffness. There was a sensation of locking when flexing or extending the right first finger. Two days before evaluation, the patient had a temporal headache on the right side that resolved. He reported no numbness or weakness.
The patient had a history of presbyopia. He had not undergone any surgeries, was not currently taking any medications, and had no known allergies. He was born and raised in a country in Eurasia and had lived in the United States for 20 years. He traveled internationally for his work as a university professor. He was divorced and lived with his two children in a house in New England. He had smoked a half pack of cigarettes for 5 years but had quit smoking 20 years earlier. He drank alcohol rarely and did not use illicit drugs. His parents were alive and well, both of his grandmothers had had breast cancer, and there was no family history of ocular or autoimmune disease.
Laboratory evaluation revealed normocytic anemia and elevated levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Results of tests of kidney and thyroid function were normal, as were blood levels of electrolytes, calcium, glucose, glycated hemoglobin, creatine kinase, homocysteine, and lipoprotein(a). Testing for antinuclear antibodies was negative, and levels of IgG subclasses were normal. Other laboratory test results are shown in Table 1. Aspirin was administered, along with empirical treatment with intravenous methylprednisolone, and the patient was admitted to the hospital.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Hillary R. Kelly: Magnetic resonance imaging (MRI) of the head and orbits (Figure 1), performed before and after the administration of intravenous contrast material, revealed enlargement of the right medial rectus muscle with stranding of the adjacent extraconal fat, as well as an enhancing masslike lesion in the left anterior superior orbit, abutting the left lacrimal gland. The masslike lesion showed a hypointense signal on short-tau inversion recovery imaging. The brain parenchyma was normal. Magnetic resonance angiography of the head and neck was normal, as was ultrasonography of the temporal arteries. Ultrasonography of the abdomen revealed markedly heterogeneous liver parenchyma and an enlarged periportal lymph node, measuring 2 cm in largest dimension. Computed tomography (CT) of the chest, abdomen, and pelvis (Figure 1), performed after the administration of intravenous contrast material, revealed multiple punctate calcifications throughout the liver and hypoattenuation of the right hepatic lobe, as well as diffuse coalescent mesenteric and retroperitoneal lymphadenopathy with coarse calcifications. There was a prominent right hilar lymph node, measuring 10 mm in diameter. The lung parenchyma was unremarkable.	
Figure 1 Figure 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Serling-Boyd: On the second hospital day, diplopia occurred when the patient looked to the far right. On examination, there was mild limitation of abduction of the right eye. After a second dose of intravenous methylprednisolone was administered, the patient chose to leave the hospital against medical advice. After discharge, he took prednisone daily. During the next week, additional laboratory test results became available. Testing for antineutrophil cytoplasmic antibodies (ANCAs) was negative. Blood testing for blastomyces antigen, coccidioides antibodies, and histoplasma antibodies was negative, as was an interferon-[gamma] release assay for Mycobacterium tuberculosis.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old man was evaluated at this hospital because of transient vision loss.
The patient had been in his usual state of good health until 1 hour before evaluation, when he noticed white ""sparkles"" flickering in the vision of the left eye, followed by sudden blurriness. He had no floaters or eye pain. During the next 2 minutes, the blurry vision worsened and became ""dark,"" such that the patient could not see a hand in front of his face when he covered the right eye. He presented to this hospital for evaluation, arriving 1 hour after the onset of vision symptoms.
On presentation, the patient noted that the vision in the left eye was improving but remained blurry. The temperature was 36.7[degrees]C, the blood pressure 120/65 mm Hg, the heart rate 92 beats per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.2. Visual acuity was 20/20 in the right eye and was limited to hand motions at 0.9 m (3.0 ft) in the left eye; 2 hours later, visual acuity in the left eye was 20/40 for distance vision and 20/30 with correction for near vision. Results of the Ishihara color test were normal. The pupils were equal, round, and reactive to light, with no relative afferent pupillary defect. Extraocular movements were intact; visual fields were full in response to confrontation. Intraocular pressure and results of a slit-lamp examination of the anterior and posterior segments of the eye were normal bilaterally. There was severe ptosis of the left upper eyelid (margin reflex distance, 4 mm in the right eye and 1 mm in the left eye). A dilated fundus examination revealed normal optic disks, maculae, and vessels. A nontender, irregular mass was palpable under the left superior orbital rim, but there was no proptosis. The temporal arteries were prominent bilaterally, more so on the right side than on the left side, with normal pulsations and no tenderness. There was no tenderness of the scalp or temporomandibular joints. The remainder of the physical examination was normal.
A review of systems was notable for fatigue and weight loss of 4.5 kg in the past year, which the patient attributed to inactivity and decreased appetite. There was a 2-month history of bilateral jaw pain with chewing of firm foods but not with soft foods. There was lateral hip soreness in both hips after walking but no stiffness. There was a sensation of locking when flexing or extending the right first finger. Two days before evaluation, the patient had a temporal headache on the right side that resolved. He reported no numbness or weakness.
The patient had a history of presbyopia. He had not undergone any surgeries, was not currently taking any medications, and had no known allergies. He was born and raised in a country in Eurasia and had lived in the United States for 20 years. He traveled internationally for his work as a university professor. He was divorced and lived with his two children in a house in New England. He had smoked a half pack of cigarettes for 5 years but had quit smoking 20 years earlier. He drank alcohol rarely and did not use illicit drugs. His parents were alive and well, both of his grandmothers had had breast cancer, and there was no family history of ocular or autoimmune disease.
Laboratory evaluation revealed normocytic anemia and elevated levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Results of tests of kidney and thyroid function were normal, as were blood levels of electrolytes, calcium, glucose, glycated hemoglobin, creatine kinase, homocysteine, and lipoprotein(a). Testing for antinuclear antibodies was negative, and levels of IgG subclasses were normal. Other laboratory test results are shown in Table 1. Aspirin was administered, along with empirical treatment with intravenous methylprednisolone, and the patient was admitted to the hospital.	
Table 1 Table 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Hillary R. Kelly: Magnetic resonance imaging (MRI) of the head and orbits (Figure 1), performed before and after the administration of intravenous contrast material, revealed enlargement of the right medial rectus muscle with stranding of the adjacent extraconal fat, as well as an enhancing masslike lesion in the left anterior superior orbit, abutting the left lacrimal gland. The masslike lesion showed a hypointense signal on short-tau inversion recovery imaging. The brain parenchyma was normal. Magnetic resonance angiography of the head and neck was normal, as was ultrasonography of the temporal arteries. Ultrasonography of the abdomen revealed markedly heterogeneous liver parenchyma and an enlarged periportal lymph node, measuring 2 cm in largest dimension. Computed tomography (CT) of the chest, abdomen, and pelvis (Figure 1), performed after the administration of intravenous contrast material, revealed multiple punctate calcifications throughout the liver and hypoattenuation of the right hepatic lobe, as well as diffuse coalescent mesenteric and retroperitoneal lymphadenopathy with coarse calcifications. There was a prominent right hilar lymph node, measuring 10 mm in diameter. The lung parenchyma was unremarkable.	
Figure 1 Figure 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Serling-Boyd: On the second hospital day, diplopia occurred when the patient looked to the far right. On examination, there was mild limitation of abduction of the right eye. After a second dose of intravenous methylprednisolone was administered, the patient chose to leave the hospital against medical advice. After discharge, he took prednisone daily. During the next week, additional laboratory test results became available. Testing for antineutrophil cytoplasmic antibodies (ANCAs) was negative. Blood testing for blastomyces antigen, coccidioides antibodies, and histoplasma antibodies was negative, as was an interferon-[gamma] release assay for Mycobacterium tuberculosis.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of transient vision loss, fatigue, weight loss, jaw pain, and hip soreness, along with the physical findings of a mass under the left superior orbital rim and prominent temporal arteries, suggest a systemic inflammatory condition. The laboratory findings of normocytic anemia and elevated liver enzymes further support this. The MRI findings of an enhancing masslike lesion in the left anterior superior orbit and enlargement of the right medial rectus muscle suggest an inflammatory process. The CT findings of multiple punctate calcifications throughout the liver, hypoattenuation of the right hepatic lobe, and diffuse coalescent mesenteric and retroperitoneal lymphadenopathy with coarse calcifications suggest a granulomatous disease. The negative results for antinuclear antibodies and antineutrophil cytoplasmic antibodies, as well as for blastomyces antigen, coccidioides antibodies, and histoplasma antibodies, rule out autoimmune diseases and certain fungal infections. The patient's history of international travel and the finding of an enlarged periportal lymph node on abdominal ultrasonography raise the possibility of a parasitic infection. \n\nDiagnosis: Granulomatous disease, possibly due to a parasitic infection.""
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        ""content"": ""The patient's symptoms of transient vision loss, fatigue, weight loss, jaw pain, and hip soreness, along with the physical findings of an irregular mass under the left superior orbital rim and prominent temporal arteries, suggest a systemic inflammatory condition. The laboratory findings of normocytic anemia and elevated liver enzymes further support this. The MRI findings of an enhancing masslike lesion in the left anterior superior orbit and enlargement of the right medial rectus muscle suggest an inflammatory process affecting the eyes. The CT findings of multiple punctate calcifications throughout the liver, hypoattenuation of the right hepatic lobe, and diffuse coalescent mesenteric and retroperitoneal lymphadenopathy with coarse calcifications suggest a systemic process. The negative results for antinuclear antibodies, IgG subclasses, and antineutrophil cytoplasmic antibodies rule out many autoimmune conditions. The negative results for blastomyces antigen, coccidioides antibodies, histoplasma antibodies, and Mycobacterium tuberculosis rule out these infectious causes. Given the patient's symptoms, physical findings, and imaging results, the most likely diagnosis is a systemic vasculitis, specifically Giant Cell Arteritis (GCA). This condition often presents with vision loss, jaw claudication, and prominent temporal arteries. The presence of anemia and elevated liver enzymes are also consistent with this diagnosis.\n\nDiagnosis: Giant Cell Arteritis (GCA)""
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        ""content"": ""The patient is a 48-year-old man presenting with transient vision loss, fatigue, weight loss, jaw pain, and hip soreness. He also has an irregular mass under the left superior orbital rim and elevated liver enzymes. The differential diagnosis for this patient includes Giant Cell Arteritis (GCA), orbital pseudotumor, sarcoidosis, and malignancy. GCA is less likely given the patient's age (GCA typically affects individuals over 50), lack of scalp tenderness, and negative temporal artery ultrasound. Orbital pseudotumor usually presents with pain, which this patient does not have. Sarcoidosis could explain the patient's systemic symptoms, eye involvement, and liver abnormalities, but the patient lacks respiratory symptoms, which are common in sarcoidosis. Malignancy could also explain the patient's systemic symptoms and the mass under the orbital rim. The presence of multiple punctate calcifications throughout the liver and diffuse coalescent mesenteric and retroperitoneal lymphadenopathy with coarse calcifications seen on imaging are suggestive of a granulomatous disease or malignancy. Given the patient's systemic symptoms, eye involvement, liver abnormalities, and imaging findings, sarcoidosis is the most likely diagnosis.\n\nDiagnosis: Sarcoidosis.""
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10.1056/NEJMcpc2027086,Case 2-2021: A 26-Year-Old Pregnant Woman with Ventricular Tachycardia and Shock,"Hemoglobin (g/dl) 11.2–15.7 10.9 11.0   9.6
Hematocrit (%) 34.1–44.9 32.5 33.1   28.2
Platelet count (per μl)   132,000 190,000   158
White-cell count (per μl) 3980–10,040 8920 12,670   19,500
Differential count (per μl)
Neutrophils 1400–7700 6333 5448   16,302
Lymphocytes 110 00 892 3928   1014
Eosinophils 0–700 89 127   0
Bands 0–4 714 1140  00 838
Sodium (mmol/liter)   135 142   143
Potassium (mmol/liter) 3.5–5.1 3.6 3.8   4.0
Chloride (mmol/liter) 98–107 102 108   109
Carbon dioxide (mmol/liter) 21–32 20 19   21
Urea nitrogen (mg/dl) 7–18 9 8   9
Creatinine (mg/dl) 0.55–1.02 0.57 1.0   0.67
Glucose (mg/dl) 74–100 98 152   202
Calcium (mg/dl) 8.5–10.1 7.9 7.5   6.7
Total protein (g/dl) 6.4–8.2 4.9 5.0 6. .3 3.6
Albumin (g/dl)   1.9 1.6   1.9
Aspartate aminotransferase 
(U/liter)
5–37 26 44   648
Alanine aminotransferase 
(U/liter)
7–65 25 31   101
Alkaline phosphatase (U/liter) 45–117 142 141   132
Total bilirubin (mg/dl) 0.2–1.0 0.59 0.28  0.8
Magnesium (mg/dl) 1.6–2.6 2.0   1.8
Prothrombin time (sec) 9.5–12.1 10.1   15.0
International normalized ratio 0.91–1.16 0.97   1.2
Partial-thromboplastin time 
(sec)
23.9–31.3 73.8 22. 5.0 >150.0
Central venous oxygen satura‚Äë
tion (%)
7 0 76.9
Phosphorus (mg/dl)   4.1
Ionized calcium (mmol/liter)   0.96
Globulin (g/dl)   1.3
Lactic acid (mmol/liter)   1.3
Troponin T (ng/ml) <0.03 28.32
Creatine kinase (U/liter)   11,012
Creatine kinase MB isoenzyme 
(U/liter)
0.  552.0
Fibrinogen (mg/dl) 15 0    259                                                                               Arterial blood gases
Fraction of inspired oxygen 1.0 1.0
pH   7.19   7.31
Partial pressure of carbon 
dioxide (mm Hg)
  42.7   42
Partial pressure of oxygen 
(mm Hg)
75–100 251.9        449","Pregnancy-associated myocardial infarction, 
probably due to spontaneous coronary-artery 
dissection.",Cardiomyopathy most likely due to myocarditis or myocardial infarction.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 26-year-old pregnant woman was transferred to this hospital for evaluation and treatment of cardiogenic shock after a cardiac arrest resulting from ventricular tachycardia.
The patient had had two previous uncomplicated pregnancies and was currently pregnant at 32 weeks of gestation with monochorionic, diamniotic twins. Her pregnancy had been monitored for polyhydramnios by her obstetrician with the use of serial fetal ultrasonography.
Three weeks before presentation to this hospital, one of the patient's preschool-age children had an ear infection and the other had a sore throat. The patient had erythema in the eyes with greenish drainage, for which topical erythromycin and sulfacetamide were prescribed. One week later, a nonproductive cough complicated by a sore throat and ear pain developed. The patient also noted new edema in her legs that was not associated with pain, redness, or warmth. However, during the subsequent week, progressive pain in her right leg occurred, which prompted her to seek care at an emergency department of another hospital.
On examination, the temperature was 37.0[degrees]C, the pulse 113 beats per minute, and the blood pressure 90/50 mm Hg. Pitting edema of the legs was noted, with no associated erythema, warmth, or tenderness on palpation of the calves. Ultrasonography of the right leg reportedly showed no evidence of deep-vein thrombosis, and a rapid test for streptococcal antigen was negative. While the patient was in the emergency department, painful uterine contractions with back discomfort developed; the cervix was 2 cm dilated. She was admitted to the labor and delivery unit for management of preterm labor. Intramuscular betamethasone and magnesium sulfate were administered for maturation of the fetal lungs and tocolysis, respectively. Continuous intravenous infusion of lactated Ringer's solution was initiated. Subcutaneous heparin was not administered, because delivery was thought to be imminent. After 24 hours of magnesium sulfate therapy, the uterine contractions remained unchanged, and no further cervical dilatation was noted. Because of concern about preterm labor, she remained hospitalized, with continuous monitoring of the fetal heart rate.
Five days after admission to the labor and delivery unit, the patient had tenderness in the left leg, and the edema in both legs had worsened. She also had episodes of severe coughing but reported no chest pain or shortness of breath. On examination, the temperature was 36.9[degrees]C, the pulse 110 beats per minute, the blood pressure 96/51 mm Hg, and the oxygen saturation 98% while the patient was breathing ambient air. Auscultation of the lungs revealed expiratory wheezes. Laboratory test results are shown in Table 1. Doppler ultrasound examination of the legs revealed an occlusive thrombus in the left peroneal vein. The hematology service was consulted, and an intravenous heparin infusion was initiated. Intravenous furosemide and oral azithromycin and guaifenesin were also administered.	
Table 1
The next morning, after the patient had eaten breakfast, she had sudden severe, ""crushing"" chest pain and became unresponsive and pulseless. Telemetry revealed monomorphic ventricular tachycardia at a rate of 178 beats per minute, with a right bundle-branch block pattern with a superior axis. Cardiopulmonary resuscitation was initiated, and after the administration of epinephrine and cardioversion, the return of spontaneous circulation was achieved within 4 minutes. Intravenous infusions of norepinephrine, vasopressin, dopamine, propofol, and fentanyl were administered. The trachea was intubated, and ventilatory support was initiated. An emergency cesarean section was performed, and two healthy male infants were delivered, with an estimated intraoperative blood loss of 1600 ml. Laboratory test results are shown in Table 1.
Dr. Andrew S. Fox: Computed tomography (CT) of the chest (Figure 1A and 1B), performed after the administration of intravenous contrast material, revealed diffuse ground-glass opacities with interlobular septal thickening, findings that were consistent with pulmonary edema; bilateral pleural effusions and pericardial effusion; cardiomegaly with biventricular enlargement; and dilatation of the main pulmonary artery, which measured 3.8 cm in diameter. No pulmonary embolus was identified.	
Figure 1 
Dr. Thomas: A transthoracic echocardiogram showed biventricular dilatation and severely decreased biventricular systolic function, moderate mitral and tricuspid regurgitation, and a small circumferential pericardial effusion. Furosemide was administered intravenously, and the patient was transferred to a nearby tertiary care center for further treatment.
On arrival at the second hospital, 210 minutes after the cardiac arrest, the pulse was 177 beats per minute, and the mean arterial pressure was 65 mm Hg while the patient was receiving intravenous infusions of norepinephrine, dopamine, and vasopressin. Physical examination was notable for diffusely coarse breath sounds, rapid regular heart sounds, and generalized edema. Thirty minutes after arrival at the second hospital, the patient underwent cannulation for femoral venoarterial extracorporeal membrane oxygenation (ECMO), and an intravenous infusion of milrinone was initiated. Ventricular tachycardia recurred; intravenous magnesium and lidocaine were administered, and the arrhythmia was terminated with cardioversion. Plans were made to transfer the patient by helicopter to this hospital, and intravenous vecuronium was given in preparation for transport. During the flight, severe vaginal bleeding developed, and 2 units of packed red cells were transfused; however, the heparin infusion was continued, given the presence of the ECMO circuit.
On arrival at this hospital, 10 hours after the cardiac arrest, additional information was obtained from the patient's sister and grandmother. The patient had a history of childhood asthma, obesity, anxiety, and depression. She had previously delivered two healthy, full-term children; her current pregnancy was complicated by gestational diabetes mellitus and polyhydramnios of one of the fetuses. Her medication history included insulin, inhaled albuterol, sertraline, iron sulfate, and folic acid. She had had no known adverse drug reactions. She did not smoke tobacco, drink alcohol, or use illicit drugs. She was married and had two healthy preschool-age children, in addition to her two newborns. Her mother had died from ovarian cancer; her sister was healthy.
On examination, the temperature was 36.2[degrees]C, the pulse 123 beats per minute, and the mean arterial pressure 76 mm Hg without intrinsic arterial pulsatility while the patient was receiving ECMO support. The respiratory rate was 16 breaths per minute and the oxygen saturation 99% while the patient was receiving oxygen through volume assist-control mechanical ventilation, with a delivered tidal volume of 290 ml and a fraction of inspired oxygen of 1.0. The weight was 105 kg, the height 163 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 39.5. The central venous pressure was 4 mm Hg. The pupils were equal and briskly reactive to light; once the patient was weaned off propofol, she was able to follow commands and move her arms and legs. Breath sounds were coarse bilaterally and diminished at the bases. Heart sounds were distant. The abdomen was soft and obese; no active bleeding was noted from the surgical incision, but large-volume vaginal bleeding and clots were observed. The arms and legs were warm and had moderate symmetric pitting edema. The femoral venous and arterial cannulas were secured in place in the right groin. The blood level of thyrotropin was normal; other laboratory test results are shown in Table 1. Tests for influenza viruses, adenovirus, human metapneumovirus, and parainfluenza virus were negative.
Dr. Fox: Chest radiography (Figure 1C), performed at the time of transfer to this hospital, revealed interstitial opacities, a small left pleural effusion, and a dense retrocardiac opacity on the left side. The venous ECMO drainage cannula and a central venous catheter were visible in the right atrium.
Dr. Thomas: An electrocardiogram (Figure 2A) showed normal sinus rhythm, right bundle-branch block, borderline-low QRS voltage, and Q waves with T-wave inversions in the anterior and lateral leads.	
Figure 2
Dr. Doreen DeFaria Yeh: Transthoracic echocardiography (Figure 2B; and Videos 1 and 2, available with the full text of this article at
NEJM.org
), performed while the patient was receiving ECMO support, revealed a dilated left ventricular cavity with normal wall thickness and severe diffuse left ventricular hypokinesis that was most prominent in the anterior, anteroseptal, and lateral territories, with an estimated ejection fraction of 11%. Additional notable findings included moderate mitral and tricuspid regurgitation, moderate right ventricular dysfunction and dilatation, an estimated pulmonary-artery systolic pressure of 53 mm Hg, a small pericardial effusion, and a pleural effusion. The ECMO inflow cannula was visualized in the inferior vena cava, and consistent with systemic ECMO blood flows, the aortic valve was observed not to open during the cardiac cycle, which suggested very poor native left ventricular contraction. There was no evidence of intracardiac shunting.
Dr. Thomas: The dose of milrinone was increased, and the dopamine infusion was discontinued. An oxytocin infusion and rectal misoprostol were administered. Ongoing large-volume vaginal bleeding was observed, and an intrauterine balloon was placed to control the bleeding.
A diagnosis and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 26-year-old pregnant woman was transferred to this hospital for evaluation and treatment of cardiogenic shock after a cardiac arrest resulting from ventricular tachycardia.
The patient had had two previous uncomplicated pregnancies and was currently pregnant at 32 weeks of gestation with monochorionic, diamniotic twins. Her pregnancy had been monitored for polyhydramnios by her obstetrician with the use of serial fetal ultrasonography.
Three weeks before presentation to this hospital, one of the patient's preschool-age children had an ear infection and the other had a sore throat. The patient had erythema in the eyes with greenish drainage, for which topical erythromycin and sulfacetamide were prescribed. One week later, a nonproductive cough complicated by a sore throat and ear pain developed. The patient also noted new edema in her legs that was not associated with pain, redness, or warmth. However, during the subsequent week, progressive pain in her right leg occurred, which prompted her to seek care at an emergency department of another hospital.
On examination, the temperature was 37.0[degrees]C, the pulse 113 beats per minute, and the blood pressure 90/50 mm Hg. Pitting edema of the legs was noted, with no associated erythema, warmth, or tenderness on palpation of the calves. Ultrasonography of the right leg reportedly showed no evidence of deep-vein thrombosis, and a rapid test for streptococcal antigen was negative. While the patient was in the emergency department, painful uterine contractions with back discomfort developed; the cervix was 2 cm dilated. She was admitted to the labor and delivery unit for management of preterm labor. Intramuscular betamethasone and magnesium sulfate were administered for maturation of the fetal lungs and tocolysis, respectively. Continuous intravenous infusion of lactated Ringer's solution was initiated. Subcutaneous heparin was not administered, because delivery was thought to be imminent. After 24 hours of magnesium sulfate therapy, the uterine contractions remained unchanged, and no further cervical dilatation was noted. Because of concern about preterm labor, she remained hospitalized, with continuous monitoring of the fetal heart rate.
Five days after admission to the labor and delivery unit, the patient had tenderness in the left leg, and the edema in both legs had worsened. She also had episodes of severe coughing but reported no chest pain or shortness of breath. On examination, the temperature was 36.9[degrees]C, the pulse 110 beats per minute, the blood pressure 96/51 mm Hg, and the oxygen saturation 98% while the patient was breathing ambient air. Auscultation of the lungs revealed expiratory wheezes. Laboratory test results are shown in Table 1. Doppler ultrasound examination of the legs revealed an occlusive thrombus in the left peroneal vein. The hematology service was consulted, and an intravenous heparin infusion was initiated. Intravenous furosemide and oral azithromycin and guaifenesin were also administered.	
Table 1
The next morning, after the patient had eaten breakfast, she had sudden severe, ""crushing"" chest pain and became unresponsive and pulseless. Telemetry revealed monomorphic ventricular tachycardia at a rate of 178 beats per minute, with a right bundle-branch block pattern with a superior axis. Cardiopulmonary resuscitation was initiated, and after the administration of epinephrine and cardioversion, the return of spontaneous circulation was achieved within 4 minutes. Intravenous infusions of norepinephrine, vasopressin, dopamine, propofol, and fentanyl were administered. The trachea was intubated, and ventilatory support was initiated. An emergency cesarean section was performed, and two healthy male infants were delivered, with an estimated intraoperative blood loss of 1600 ml. Laboratory test results are shown in Table 1.
Dr. Andrew S. Fox: Computed tomography (CT) of the chest (Figure 1A and 1B), performed after the administration of intravenous contrast material, revealed diffuse ground-glass opacities with interlobular septal thickening, findings that were consistent with pulmonary edema; bilateral pleural effusions and pericardial effusion; cardiomegaly with biventricular enlargement; and dilatation of the main pulmonary artery, which measured 3.8 cm in diameter. No pulmonary embolus was identified.	
Figure 1 
Dr. Thomas: A transthoracic echocardiogram showed biventricular dilatation and severely decreased biventricular systolic function, moderate mitral and tricuspid regurgitation, and a small circumferential pericardial effusion. Furosemide was administered intravenously, and the patient was transferred to a nearby tertiary care center for further treatment.
On arrival at the second hospital, 210 minutes after the cardiac arrest, the pulse was 177 beats per minute, and the mean arterial pressure was 65 mm Hg while the patient was receiving intravenous infusions of norepinephrine, dopamine, and vasopressin. Physical examination was notable for diffusely coarse breath sounds, rapid regular heart sounds, and generalized edema. Thirty minutes after arrival at the second hospital, the patient underwent cannulation for femoral venoarterial extracorporeal membrane oxygenation (ECMO), and an intravenous infusion of milrinone was initiated. Ventricular tachycardia recurred; intravenous magnesium and lidocaine were administered, and the arrhythmia was terminated with cardioversion. Plans were made to transfer the patient by helicopter to this hospital, and intravenous vecuronium was given in preparation for transport. During the flight, severe vaginal bleeding developed, and 2 units of packed red cells were transfused; however, the heparin infusion was continued, given the presence of the ECMO circuit.
On arrival at this hospital, 10 hours after the cardiac arrest, additional information was obtained from the patient's sister and grandmother. The patient had a history of childhood asthma, obesity, anxiety, and depression. She had previously delivered two healthy, full-term children; her current pregnancy was complicated by gestational diabetes mellitus and polyhydramnios of one of the fetuses. Her medication history included insulin, inhaled albuterol, sertraline, iron sulfate, and folic acid. She had had no known adverse drug reactions. She did not smoke tobacco, drink alcohol, or use illicit drugs. She was married and had two healthy preschool-age children, in addition to her two newborns. Her mother had died from ovarian cancer; her sister was healthy.
On examination, the temperature was 36.2[degrees]C, the pulse 123 beats per minute, and the mean arterial pressure 76 mm Hg without intrinsic arterial pulsatility while the patient was receiving ECMO support. The respiratory rate was 16 breaths per minute and the oxygen saturation 99% while the patient was receiving oxygen through volume assist-control mechanical ventilation, with a delivered tidal volume of 290 ml and a fraction of inspired oxygen of 1.0. The weight was 105 kg, the height 163 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 39.5. The central venous pressure was 4 mm Hg. The pupils were equal and briskly reactive to light; once the patient was weaned off propofol, she was able to follow commands and move her arms and legs. Breath sounds were coarse bilaterally and diminished at the bases. Heart sounds were distant. The abdomen was soft and obese; no active bleeding was noted from the surgical incision, but large-volume vaginal bleeding and clots were observed. The arms and legs were warm and had moderate symmetric pitting edema. The femoral venous and arterial cannulas were secured in place in the right groin. The blood level of thyrotropin was normal; other laboratory test results are shown in Table 1. Tests for influenza viruses, adenovirus, human metapneumovirus, and parainfluenza virus were negative.
Dr. Fox: Chest radiography (Figure 1C), performed at the time of transfer to this hospital, revealed interstitial opacities, a small left pleural effusion, and a dense retrocardiac opacity on the left side. The venous ECMO drainage cannula and a central venous catheter were visible in the right atrium.
Dr. Thomas: An electrocardiogram (Figure 2A) showed normal sinus rhythm, right bundle-branch block, borderline-low QRS voltage, and Q waves with T-wave inversions in the anterior and lateral leads.	
Figure 2
Dr. Doreen DeFaria Yeh: Transthoracic echocardiography (Figure 2B; and Videos 1 and 2, available with the full text of this article at
NEJM.org
), performed while the patient was receiving ECMO support, revealed a dilated left ventricular cavity with normal wall thickness and severe diffuse left ventricular hypokinesis that was most prominent in the anterior, anteroseptal, and lateral territories, with an estimated ejection fraction of 11%. Additional notable findings included moderate mitral and tricuspid regurgitation, moderate right ventricular dysfunction and dilatation, an estimated pulmonary-artery systolic pressure of 53 mm Hg, a small pericardial effusion, and a pleural effusion. The ECMO inflow cannula was visualized in the inferior vena cava, and consistent with systemic ECMO blood flows, the aortic valve was observed not to open during the cardiac cycle, which suggested very poor native left ventricular contraction. There was no evidence of intracardiac shunting.
Dr. Thomas: The dose of milrinone was increased, and the dopamine infusion was discontinued. An oxytocin infusion and rectal misoprostol were administered. Ongoing large-volume vaginal bleeding was observed, and an intrauterine balloon was placed to control the bleeding.
A diagnosis and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""This is a pregnant woman who presents with cardiogenic shock after a cardiac arrest resulting from ventricular tachycardia. She had a history of childhood asthma, obesity, anxiety, and depression. Her current pregnancy was complicated by gestational diabetes mellitus and polyhydramnios of one of the fetuses. The differential diagnosis for this patient includes peripartum cardiomyopathy, myocarditis, pulmonary embolism, and acute coronary syndrome. The patient\u2019s CT scan of the chest did not reveal a pulmonary embolus, making pulmonary embolism less likely. The patient\u2019s EKG showed normal sinus rhythm, right bundle-branch block, borderline-low QRS voltage, and Q waves with T-wave inversions in the anterior and lateral leads. This is not characteristic of acute coronary syndrome, making it less likely. The patient\u2019s echocardiogram revealed a dilated left ventricular cavity with normal wall thickness and severe diffuse left ventricular hypokinesis that was most prominent in the anterior, anteroseptal, and lateral territories, with an estimated ejection fraction of 11%. This is characteristic of peripartum cardiomyopathy. Furthermore, the patient\u2019s other symptoms of edema in her legs and a nonproductive cough are supportive of heart failure. \n\nDiagnosis:\nPeripartum cardiomyopathy is the most likely diagnosis.""
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10.1056/NEJMcpc2027084,Case 1-2021: A 76-Year-Old Woman with Lethargy and Altered Mental Status,"White-cell count (per μl)   5800   4480
Differential count (per μl)
Neutrophils 1600–6100 4580   3340
Lymphocytes 120 700 640   460
Monocytes 20 00 450   550
Eosinophils 40–540 80   50
Basophils 1 0 20  00 10
Hemoglobin (g/dl) 11.2–15.7 8.6   9.2
Hematocrit (%) 34–45 26   27.6
Platelet count (per μl)   110,000   126,000
Sodium (mmol/liter)   130   136
Potassium (mmol/liter) 3.5–5.4 4.7   3.0
Chloride (mmol/liter) 96–108 100   95
Carbon dioxide (mmol/liter) 22–32 17   30
Anion gap (mmol/liter) 10–18 13   11
Urea nitrogen (mg/dl) 6–20 83   20
Creatinine (mg/dl) 0.4–1.1 4.9   1.99
Glucose (mg/dl) 70–100 118   138
Calcium (mg/dl) 8.4–10.3 7.6   8.3
N-terminal pro–B-type natriuretic 
peptide (pg/ml)
  47,920
Alanine aminotransferase (U/liter)   26
Aspartate aminotransferase (U/liter)   33
Alkaline phosphatase (U/liter)   144
Lactic acid (mmol/liter)   0.5",Mycobacterium tuberculosis meningitis,Disseminated tuberculosis with associated central nervous system vasculitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old woman was transferred to this hospital because of lethargy and altered mental status.
The patient had been well until 2 months before this evaluation, when she was admitted to another hospital for community-acquired pneumonia. Empirical treatment with ceftriaxone and azithromycin was administered, and her condition partially improved.
Two weeks later, the patient presented to the other hospital with recurrent dyspnea and lethargy. A partly loculated right pleural effusion was identified. Empirical treatment with vancomycin and piperacillin-tazobactam was administered intravenously. Thoracostomy (placement of a chest tube for drainage) was performed, and pleural fluid analysis revealed an exudative pleural effusion; Gram's staining showed no neutrophils or microorganisms, culture showed no growth, and cytologic testing showed no malignant cells. After a 1-week admission, the dyspnea abated, and the patient was discharged with instructions to complete a 2-week course of antibiotic therapy.
Two weeks before this evaluation, generalized weakness and lethargy developed, along with new diffuse headache. The patient's family thought that she appeared somnolent and ""clumsy"" while walking. Four days later, her family took her to the other hospital for evaluation. A review of systems was notable for dyspnea, leg edema, and hematochezia and no fever, chills, chest pain, cough, dysuria, hematuria, or melena. The temperature was 37.2[degrees]C, the heart rate 74 beats per minute, the blood pressure 176/101 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while she was receiving oxygen through a nasal cannula at a rate of 2 liters per minute. The patient was alert and oriented but appeared to be confused when recalling recent events. She had jugular venous distention, diffuse lung rales, and 2+ symmetric pitting edema of the lower legs up to the knees. The blood urea nitrogen level was 83 mg per deciliter (29.6 mmol per liter; reference range, 6 to 20 mg per deciliter [2.1 to 7.1 mmol per liter]), the creatinine level 4.9 mg per deciliter (433 [mu]mol per liter; reference range, 0.4 to 1.1 mg per deciliter [35 to 97 [mu]mol per liter]), and the hematocrit 26% (reference range, 34 to 45). Other laboratory test results are shown in Table 1.	
Table 1 
Dr. R. Gilberto Gonzalez: Chest radiography revealed a small right pleural effusion and moderate interstitial pulmonary edema. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed a chronic subcortical infarct of the right frontal lobe, as well as diffuse involutional changes and nonspecific white-matter hypodensities.
Dr. Merali: Oral labetalol, clonidine, and hydralazine and intravenous furosemide were administered to treat possible hypertensive emergency. During the next 2 days, the patient's headache and anemia worsened and dizziness developed. On the seventh hospital day, there was an acute episode of nonbloody emesis, followed by a generalized tonic-clonic seizure lasting 1 minute. The patient was transferred to the intensive care unit (ICU) of the other hospital.
Dr. Gonzalez: Repeat CT of the head, performed without the administration of intravenous contrast material, revealed findings similar to those of the previous study. Magnetic resonance imaging (MRI) of the head (Figure 1), performed without the administration of intravenous contrast material, revealed two foci of restricted diffusion in the right frontal lobe and the left cerebellar hemisphere, each measuring 1 cm in diameter, with surrounding signal hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. In addition, there was diffuse ventricular enlargement, with surrounding smooth hyperintensity on T2-weighted and FLAIR images; this finding is suggestive of communicating hydrocephalus with transependymal flow of cerebrospinal fluid (CSF). T2-weighted and FLAIR images also showed multiple foci of hyperintensity scattered throughout the deep white matter.	
Figure 1 
Dr. Merali: Video electroencephalography revealed epileptiform discharges predominantly in the frontal lobe, with generalized slowing. Levetiracetam, vancomycin, and ceftazidime were administered; intermittent hemodialysis was initiated.
During the next 3 days, the patient began to have a right gaze preference, left hemineglect, and aphasia. The temperature increased to 39.4[degrees]C, and chills developed. Blood specimens were obtained for microbiologic culture. Lumbar puncture was deferred, pending additional imaging studies to rule out a space-occupying lesion. Empirical treatment with vancomycin, ceftazidime, ampicillin, metronidazole, and acyclovir was administered intravenously. At the request of her family, the patient was transferred to the ICU of this hospital.
On arrival at this hospital, additional history was obtained from the patient's family. Two years earlier, the patient had received a diagnosis of gastric adenocarcinoma, which was treated with fluorouracil, leucovorin, and oxaliplatin. Therapy was discontinued after three of six cycles because of ileus, renal injury, and neutropenic fever. Robotic subtotal gastrectomy and Roux-en-Y gastric bypass were then performed; histologic examination of the resected tissue revealed a nearly complete response of the adenocarcinoma. Five months before the current evaluation, CT with 18F-fluorodeoxyglucose (FDG)-positron-emission tomography performed at the other hospital revealed FDG avidity in nonenlarged lymph nodes in the mediastinum, retroperitoneum, porta hepatis, and right cervical region. Biopsy was offered, but the patient chose to undergo active surveillance. Additional medical history included hypertension, hyperlipidemia, type 2 diabetes mellitus, hypothyroidism, and stage 5 chronic kidney disease. Medications included torsemide, amlodipine, clonidine, hydralazine, hydrochlorothiazide, labetalol, rosuvastatin, insulin, levothyroxine, cholecalciferol, mirtazapine, and oxycodone. There were no known drug allergies.
Four decades before the current admission, the patient had immigrated to the United States from an island off the west coast of Africa. She was widowed, had four children, and lived with a pet parrot in an urban area of New England. Two months before hospitalization, she had been independent in activities of daily living and had received minimal assistance, such as with buying groceries, from family members. The patient had traveled to her country of origin 8 years earlier and to South America and the Caribbean in the past year. She had had no sexual partners in the past three decades. She did not drink alcohol, smoke tobacco, or use illicit drugs. Her sister had received a diagnosis of pancreatic cancer at 60 years of age; there was no family history of rheumatologic, neurologic, cardiovascular, or renal disease.
On examination, the temperature was 36.8[degrees]C, the heart rate 93 beats per minute, the blood pressure 170/92 mm Hg, the respiratory rate 12 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 23.8. The patient was somnolent and variably oriented to self but not to situation, location, or time. She intermittently opened her eyes spontaneously but did not follow commands or reliably withdraw in response to noxious stimuli. Her face and pupils appeared symmetric; a right gaze preference and left hemineglect were present. There was no evidence of jugular venous distention, rales, or edema, and the abdominal examination was normal.
Testing for human immunodeficiency virus (HIV) type 1 and type 2 antibodies and p24 antigen was nonreactive. A test for antitreponemal antibodies was positive, and a rapid plasma reagin test was negative. Other laboratory test results are shown in Table 1.
Dr. Gonzalez: Repeat CT of the head, performed without the administration of intravenous contrast material, revealed foci of hypoattenuation in the left superior cerebellar hemisphere and the right frontal lobe that corresponded to the foci of restricted diffusion on MRI observed at the other hospital.
Dr. Merali: Empirical treatment with vancomycin, ceftriaxone, ampicillin, metronidazole, and acyclovir was administered intravenously. On the second hospital day, a lumbar puncture was performed. The opening pressure was 15 cm of water. The CSF was slightly yellow, with a glucose level of 18 mg per deciliter (1.0 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]) and a protein level of 173 mg per deciliter (reference range, 5 to 55). There were 236 nucleated cells per microliter (reference range, 0 to 5), of which 69% were neutrophils, 19% lymphocytes, and 12% monocytes. Gram's staining of the CSF showed abundant neutrophils and mononuclear cells; no organisms were identified. Transthoracic echocardiography revealed mild left ventricular hypokinesis and aortic sclerosis.
On the fourth hospital day, new right esophoria developed and the patient was less responsive. The trachea was intubated and mechanical ventilation was initiated for airway protection.
Dr. Gonzalez: Repeat MRI of the head (Figure 2), performed without the administration of intravenous contrast material, revealed enlargement of the previously observed lesions in the right frontal lobe and left cerebellum. There were additional foci of reduced diffusivity, with corresponding hyperintense signal abnormalities on T2-weighted and FLAIR images, involving both cerebral hemispheres, deep gray matter, the brain stem, and the cerebellum. Magnetic resonance angiography of the head, performed without the administration of intravenous contrast material, revealed multifocal narrowing of branches of the bilateral middle and posterior cerebral arteries. CT of the chest, abdomen, and pelvis, performed without the administration of intravenous contrast material, revealed small bilateral pleural effusions and no other abnormalities.	
Figure 2
Dr. Merali: Empirical treatment with methylprednisolone was started. The next day, repeat lumbar puncture was performed. The opening pressure was 16 cm of water. The CSF was slightly yellow, with a glucose level of 179 mg per deciliter (9.9 mmol per liter) and a protein level of 181 mg per deciliter. There were 286 nucleated cells per microliter, of which 83% were neutrophils, 9% lymphocytes, and 8% monocytes. Gram's staining of the CSF showed abundant neutrophils and moderate mononuclear cells; there were no organisms.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old woman was transferred to this hospital because of lethargy and altered mental status.
The patient had been well until 2 months before this evaluation, when she was admitted to another hospital for community-acquired pneumonia. Empirical treatment with ceftriaxone and azithromycin was administered, and her condition partially improved.
Two weeks later, the patient presented to the other hospital with recurrent dyspnea and lethargy. A partly loculated right pleural effusion was identified. Empirical treatment with vancomycin and piperacillin-tazobactam was administered intravenously. Thoracostomy (placement of a chest tube for drainage) was performed, and pleural fluid analysis revealed an exudative pleural effusion; Gram's staining showed no neutrophils or microorganisms, culture showed no growth, and cytologic testing showed no malignant cells. After a 1-week admission, the dyspnea abated, and the patient was discharged with instructions to complete a 2-week course of antibiotic therapy.
Two weeks before this evaluation, generalized weakness and lethargy developed, along with new diffuse headache. The patient's family thought that she appeared somnolent and ""clumsy"" while walking. Four days later, her family took her to the other hospital for evaluation. A review of systems was notable for dyspnea, leg edema, and hematochezia and no fever, chills, chest pain, cough, dysuria, hematuria, or melena. The temperature was 37.2[degrees]C, the heart rate 74 beats per minute, the blood pressure 176/101 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while she was receiving oxygen through a nasal cannula at a rate of 2 liters per minute. The patient was alert and oriented but appeared to be confused when recalling recent events. She had jugular venous distention, diffuse lung rales, and 2+ symmetric pitting edema of the lower legs up to the knees. The blood urea nitrogen level was 83 mg per deciliter (29.6 mmol per liter; reference range, 6 to 20 mg per deciliter [2.1 to 7.1 mmol per liter]), the creatinine level 4.9 mg per deciliter (433 [mu]mol per liter; reference range, 0.4 to 1.1 mg per deciliter [35 to 97 [mu]mol per liter]), and the hematocrit 26% (reference range, 34 to 45). Other laboratory test results are shown in Table 1.	
Table 1 
Dr. R. Gilberto Gonzalez: Chest radiography revealed a small right pleural effusion and moderate interstitial pulmonary edema. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed a chronic subcortical infarct of the right frontal lobe, as well as diffuse involutional changes and nonspecific white-matter hypodensities.
Dr. Merali: Oral labetalol, clonidine, and hydralazine and intravenous furosemide were administered to treat possible hypertensive emergency. During the next 2 days, the patient's headache and anemia worsened and dizziness developed. On the seventh hospital day, there was an acute episode of nonbloody emesis, followed by a generalized tonic-clonic seizure lasting 1 minute. The patient was transferred to the intensive care unit (ICU) of the other hospital.
Dr. Gonzalez: Repeat CT of the head, performed without the administration of intravenous contrast material, revealed findings similar to those of the previous study. Magnetic resonance imaging (MRI) of the head (Figure 1), performed without the administration of intravenous contrast material, revealed two foci of restricted diffusion in the right frontal lobe and the left cerebellar hemisphere, each measuring 1 cm in diameter, with surrounding signal hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. In addition, there was diffuse ventricular enlargement, with surrounding smooth hyperintensity on T2-weighted and FLAIR images; this finding is suggestive of communicating hydrocephalus with transependymal flow of cerebrospinal fluid (CSF). T2-weighted and FLAIR images also showed multiple foci of hyperintensity scattered throughout the deep white matter.	
Figure 1 
Dr. Merali: Video electroencephalography revealed epileptiform discharges predominantly in the frontal lobe, with generalized slowing. Levetiracetam, vancomycin, and ceftazidime were administered; intermittent hemodialysis was initiated.
During the next 3 days, the patient began to have a right gaze preference, left hemineglect, and aphasia. The temperature increased to 39.4[degrees]C, and chills developed. Blood specimens were obtained for microbiologic culture. Lumbar puncture was deferred, pending additional imaging studies to rule out a space-occupying lesion. Empirical treatment with vancomycin, ceftazidime, ampicillin, metronidazole, and acyclovir was administered intravenously. At the request of her family, the patient was transferred to the ICU of this hospital.
On arrival at this hospital, additional history was obtained from the patient's family. Two years earlier, the patient had received a diagnosis of gastric adenocarcinoma, which was treated with fluorouracil, leucovorin, and oxaliplatin. Therapy was discontinued after three of six cycles because of ileus, renal injury, and neutropenic fever. Robotic subtotal gastrectomy and Roux-en-Y gastric bypass were then performed; histologic examination of the resected tissue revealed a nearly complete response of the adenocarcinoma. Five months before the current evaluation, CT with 18F-fluorodeoxyglucose (FDG)-positron-emission tomography performed at the other hospital revealed FDG avidity in nonenlarged lymph nodes in the mediastinum, retroperitoneum, porta hepatis, and right cervical region. Biopsy was offered, but the patient chose to undergo active surveillance. Additional medical history included hypertension, hyperlipidemia, type 2 diabetes mellitus, hypothyroidism, and stage 5 chronic kidney disease. Medications included torsemide, amlodipine, clonidine, hydralazine, hydrochlorothiazide, labetalol, rosuvastatin, insulin, levothyroxine, cholecalciferol, mirtazapine, and oxycodone. There were no known drug allergies.
Four decades before the current admission, the patient had immigrated to the United States from an island off the west coast of Africa. She was widowed, had four children, and lived with a pet parrot in an urban area of New England. Two months before hospitalization, she had been independent in activities of daily living and had received minimal assistance, such as with buying groceries, from family members. The patient had traveled to her country of origin 8 years earlier and to South America and the Caribbean in the past year. She had had no sexual partners in the past three decades. She did not drink alcohol, smoke tobacco, or use illicit drugs. Her sister had received a diagnosis of pancreatic cancer at 60 years of age; there was no family history of rheumatologic, neurologic, cardiovascular, or renal disease.
On examination, the temperature was 36.8[degrees]C, the heart rate 93 beats per minute, the blood pressure 170/92 mm Hg, the respiratory rate 12 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 23.8. The patient was somnolent and variably oriented to self but not to situation, location, or time. She intermittently opened her eyes spontaneously but did not follow commands or reliably withdraw in response to noxious stimuli. Her face and pupils appeared symmetric; a right gaze preference and left hemineglect were present. There was no evidence of jugular venous distention, rales, or edema, and the abdominal examination was normal.
Testing for human immunodeficiency virus (HIV) type 1 and type 2 antibodies and p24 antigen was nonreactive. A test for antitreponemal antibodies was positive, and a rapid plasma reagin test was negative. Other laboratory test results are shown in Table 1.
Dr. Gonzalez: Repeat CT of the head, performed without the administration of intravenous contrast material, revealed foci of hypoattenuation in the left superior cerebellar hemisphere and the right frontal lobe that corresponded to the foci of restricted diffusion on MRI observed at the other hospital.
Dr. Merali: Empirical treatment with vancomycin, ceftriaxone, ampicillin, metronidazole, and acyclovir was administered intravenously. On the second hospital day, a lumbar puncture was performed. The opening pressure was 15 cm of water. The CSF was slightly yellow, with a glucose level of 18 mg per deciliter (1.0 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]) and a protein level of 173 mg per deciliter (reference range, 5 to 55). There were 236 nucleated cells per microliter (reference range, 0 to 5), of which 69% were neutrophils, 19% lymphocytes, and 12% monocytes. Gram's staining of the CSF showed abundant neutrophils and mononuclear cells; no organisms were identified. Transthoracic echocardiography revealed mild left ventricular hypokinesis and aortic sclerosis.
On the fourth hospital day, new right esophoria developed and the patient was less responsive. The trachea was intubated and mechanical ventilation was initiated for airway protection.
Dr. Gonzalez: Repeat MRI of the head (Figure 2), performed without the administration of intravenous contrast material, revealed enlargement of the previously observed lesions in the right frontal lobe and left cerebellum. There were additional foci of reduced diffusivity, with corresponding hyperintense signal abnormalities on T2-weighted and FLAIR images, involving both cerebral hemispheres, deep gray matter, the brain stem, and the cerebellum. Magnetic resonance angiography of the head, performed without the administration of intravenous contrast material, revealed multifocal narrowing of branches of the bilateral middle and posterior cerebral arteries. CT of the chest, abdomen, and pelvis, performed without the administration of intravenous contrast material, revealed small bilateral pleural effusions and no other abnormalities.	
Figure 2
Dr. Merali: Empirical treatment with methylprednisolone was started. The next day, repeat lumbar puncture was performed. The opening pressure was 16 cm of water. The CSF was slightly yellow, with a glucose level of 179 mg per deciliter (9.9 mmol per liter) and a protein level of 181 mg per deciliter. There were 286 nucleated cells per microliter, of which 83% were neutrophils, 9% lymphocytes, and 8% monocytes. Gram's staining of the CSF showed abundant neutrophils and moderate mononuclear cells; there were no organisms.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of lethargy, altered mental status, and recurrent dyspnea, along with her history of gastric adenocarcinoma, suggest a systemic disease. The presence of exudative pleural effusion and the lack of response to antibiotics suggest a non-infectious cause. The patient's neurological symptoms, including confusion, somnolence, and clumsiness, along with the findings of foci of restricted diffusion in the right frontal lobe and the left cerebellar hemisphere on MRI, suggest a central nervous system involvement. The patient's history of gastric adenocarcinoma raises the possibility of metastatic disease, but the lack of malignant cells in the pleural fluid analysis and the absence of any space-occupying lesions on imaging make this less likely. The patient's elevated temperature and chills, along with the presence of neutrophils in the CSF, suggest an inflammatory or infectious process. However, the lack of growth in cultures and the patient's lack of response to broad-spectrum antibiotics suggest a non-infectious cause. The presence of multiple foci of hyperintensity scattered throughout the deep white matter on MRI, along with the patient's symptoms of headache, anemia, and dizziness, suggest a vasculitic process. The patient's history of gastric adenocarcinoma and the presence of FDG avidity in nonenlarged lymph nodes in multiple locations on PET-CT suggest a paraneoplastic syndrome. The patient's neurological symptoms, the presence of neutrophils in the CSF, and the findings on MRI are consistent with a diagnosis of paraneoplastic limbic encephalitis, a type of paraneoplastic neurological syndrome.\n\nDiagnosis: Paraneoplastic Limbic Encephalitis.""
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        ""content"": ""The patient's symptoms of lethargy, altered mental status, and recurrent dyspnea, along with her history of gastric adenocarcinoma, suggest a systemic disease. The presence of foci of restricted diffusion in the right frontal lobe and the left cerebellar hemisphere on MRI, along with the enlargement of these lesions and the appearance of additional foci in both cerebral hemispheres, deep gray matter, the brain stem, and the cerebellum on repeat MRI, suggest a neurological condition. The patient's CSF analysis showing elevated protein and nucleated cells, predominantly neutrophils, suggests an inflammatory or infectious process. The patient's history of gastric adenocarcinoma and the presence of FDG avidity in nonenlarged lymph nodes in various regions on PET-CT raise the possibility of metastatic disease or paraneoplastic syndrome. However, the absence of malignant cells in the pleural fluid and the lack of growth in cultures argue against these possibilities. The presence of multifocal narrowing of branches of the bilateral middle and posterior cerebral arteries on magnetic resonance angiography suggests a vasculitic process. Given the patient's history of gastric adenocarcinoma, the neurological symptoms, and the findings on imaging and CSF analysis, the most likely diagnosis is paraneoplastic vasculitis.\n\nDiagnosis: Paraneoplastic Vasculitis.""
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        ""content"": ""This is a 76-year-old woman with a history of gastric adenocarcinoma who presents with altered mental status, lethargy, and headache. She also has a history of community-acquired pneumonia and a right pleural effusion. Her symptoms have worsened over the past two weeks, with the development of generalized weakness, somnolence, and clumsiness while walking. She has also developed dyspnea, leg edema, and hematochezia. Her physical examination is notable for confusion, jugular venous distention, diffuse lung rales, and pitting edema of the lower legs. Her lab results show elevated blood urea nitrogen and creatinine levels, indicating renal dysfunction, and a low hematocrit, indicating anemia. Her CT scan shows a chronic subcortical infarct of the right frontal lobe, diffuse involutional changes, and nonspecific white-matter hypodensities. Her MRI shows two foci of restricted diffusion in the right frontal lobe and the left cerebellar hemisphere, each measuring 1 cm in diameter, with surrounding signal hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. There is also diffuse ventricular enlargement, suggestive of communicating hydrocephalus with transependymal flow of cerebrospinal fluid (CSF). \n\nThe differential diagnosis for this patient includes central nervous system (CNS) infection, CNS malignancy, and CNS vasculitis. The patient's history of gastric adenocarcinoma raises the possibility of CNS metastasis. However, the presence of neutrophils in the CSF and the patient's fever suggest an infectious process. The patient's history of pneumonia and pleural effusion also support an infectious etiology. CNS vasculitis could also present with altered mental status and headache, but this is less likely given the patient's lack of other systemic symptoms of vasculitis. \n\nGiven the patient's history of gastric adenocarcinoma, the presence of neutrophils in the CSF, and the patient's fever, the most likely diagnosis is CNS infection secondary to immunosuppression from cancer. \n\nDiagnosis: Central nervous system infection secondary to immunosuppression from cancer.""
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10.1056/NEJMcpc1916251,Case 41-2020: A 62-Year-Old Man with Memory Loss and Odd Behavior,,Frontotemporal lobar degeneration with taupositive inclusions (FTLD-tau) consistent with Pick’s disease,Behavioral variant of frontotemporal dementia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 62-year-old, left-handed man was seen in the memory disorders clinic of this hospital because of memory loss, personality changes, and odd behavior.
Approximately 5 years before this evaluation, the patient's wife noticed that the patient was becoming more forgetful and napped frequently during the day. She also noticed that he lacked initiative in his professional work; for example, he was not charging or collecting payments for services. The patient's coworkers observed that he was having difficulty focusing and frequently required redirection when interacting with clients. The patient had no concerns other than intermittent mild headaches.
During the next few years, the patient's wife noticed that he became distant with family, was less talkative, and lacked interest in activities that he had previously enjoyed. He made numerous costly errors at work and also had odd behaviors. For example, he entered the kitchen of a local restaurant without permission; on another occasion, he inadvertently borrowed a vehicle from a colleague without first notifying that person. In another instance, while the patient's vehicle was stopped for a routine traffic infraction, he became irritable and briefly evaded police, incurring several legal violations.
One year before this evaluation, the patient was seen in the neurology and psychiatry clinics of another hospital at his wife's request. He had no concerns about his neurocognitive state. He noted that he was sleeping as little as 2 to 3 hours per night but had a good energy level. He reported intermittent mild headaches. He had no sinus pain, numbness, tingling, or constitutional symptoms. On examination, the patient was alert and oriented, with some inattention and confabulation. The remainder of the neurologic examination was normal. A complete blood count and blood levels of electrolytes and glucose were normal, as were results of tests of kidney, liver, and thyroid function. Tests for antinuclear antibodies and for Lyme disease were negative. The patient received diagnoses of attention deficit-hyperactivity disorder, adjustment disorder, and avoidant personality traits. Psychotherapy was initiated, and melatonin and dextroamphetamine-amphetamine were prescribed.
The patient had ongoing personality changes and difficulties with organization and daily functioning, and he was evaluated in the memory disorders clinic of this hospital at his wife's request. She reported that dextroamphetamine-amphetamine had not improved his overall organizational abilities. Although he was physically capable of conducting activities of daily living, he required prompting to perform tasks to maintain basic hygiene, such as bathing. He no longer participated in the management of family finances; he was unable to maintain employment and was receiving disability payments. He had new odd behaviors, such as urinating in public on a few occasions and frequently and unexpectedly visiting family members' workplaces and neighbors' homes at late hours. He also had obsessive behaviors, such as calling his children multiple times to confirm details before a scheduled gathering. The patient was unaware of his inappropriate and unusual behaviors. He did not report having anxiety, depression, or perceptual disturbances.
Approximately 10 years before the current evaluation, the patient had received a diagnosis of Waldenstrom's macroglobulinemia. Because he was asymptomatic, treatment was deferred. Two years before the current evaluation, computed tomography (CT) of the chest, abdomen, and pelvis was performed for disease surveillance. There were multiple enlarged hilar and retrocrural lymph nodes, measuring up to 1.2 cm in greatest dimension, with no evidence of organomegaly or focal osseous lesions. The patient attended routine oncology appointments for disease monitoring. Two months before the current evaluation, a complete blood count and a basic metabolic panel were normal. The blood IgM level was 2850 mg per deciliter (reference range, 40 to 230), and the [beta]2-microglobulin level 2.8 mg liter (reference range, 0 to 2.7); these values had been stable since the diagnosis of Waldenstrom's macroglobulinemia was established.
Other medical history included mitral regurgitation, nephrolithiasis, benign prostatic hyperplasia, bilateral knee osteoarthritis, and spinal stenosis. There was no history of head trauma, stroke, or seizure. Medications included a multivitamin and fish oil; there were no known allergies to medications. The patient did not drink alcohol, smoke tobacco, or use illicit drugs. He lived with his wife, and his daughters and grandchildren lived nearby. He had graduated from high school and trade school before serving in the navy for 2 years; he did not serve in a combat role or have known exposure to toxins. Both of his parents had heart disease, a sister had depression, and a maternal uncle had throat cancer. There was no family history of dementia, neurologic disorders, or psychiatric disorders.
On examination, the patient was well groomed, pleasant, and cooperative. Physical appearance was normal. His Mini-Mental State Examination score was 23 on a scale ranging from 0 to 30 (with higher scores indicating better cognitive function), and his Montreal Cognitive Assessment (MoCA) score was 15 on a scale ranging from 0 to 30 (with higher scores indicating better cognitive function).
Orientation was intact except for an error in recalling the date. On testing of attention, the patient had difficulty with serial sevens calculations and with the digit-span test, in which a sequence of numbers is read by the examiner and repeated by the patient; he repeated only four digits of the forward span correctly. On testing of memory, he repeated five out of five words after two trials and did not spontaneously recall any of the words after 5 minutes; he recalled three of the words when selecting from a written list of word choices. Spontaneous speech production was diminished. On testing of confrontation naming, he identified a camel when shown a picture of a giraffe. On testing of semantic and phonemic fluency, he spontaneously generated six animal names over a 1-minute period, as well as one word that begins with the letter ""F"" over a 1-minute period. The clock-drawing test showed good organization. The letter-number sequencing test (also known as the alternating trail-making test) revealed impaired set shifting, and Luria's three-step test revealed impaired motor sequencing. On testing of verbal abstraction, when the patient was asked to describe how a train and a bicycle are similar, he stated, ""A train is bigger than a bicycle and would crush the bicycle."" Judgment and insight were markedly impaired.
An evaluation of cranial nerve function, sensation, power, bulk, tone, coordination, and gait was normal. Deep-tendon reflexes were normal, and the toes were downgoing bilaterally. Bilateral grasp reflexes and palmomental reflexes were present. Testing for syphilis was negative. The blood folate level was 8.2 ng per milliliter (19 nmol per liter; reference range, >4.7 ng per milliliter [11 nmol per liter]), and the vitamin B12 level 258 pg per milliliter (190 pmol per liter; reference range, >231 pg per milliliter [170 pmol per liter]).
On neuropsychological assessment, social engagement was limited, with a few moments of giggling that was incongruent with the context. Spontaneous speech was fluent but impoverished. There was frequent use of the word ""thing"" to replace lower-frequency words and periodic use of phonemic paraphasias such as ""a fenco type of thing."" Thoughts were coherent but impoverished, tangential, and perseverative. Attention and executive functioning were markedly impaired during assessments of verbal fluency, divided attention, abstract reasoning, and inhibitory control. Visual memory was relatively intact, but verbal memory was impaired in terms of encoding and retrieval. When the patient was asked to describe an image, written language was severely impaired but oral language was relatively intact.
A diagnostic test was reviewed, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 62-year-old, left-handed man was seen in the memory disorders clinic of this hospital because of memory loss, personality changes, and odd behavior.
Approximately 5 years before this evaluation, the patient's wife noticed that the patient was becoming more forgetful and napped frequently during the day. She also noticed that he lacked initiative in his professional work; for example, he was not charging or collecting payments for services. The patient's coworkers observed that he was having difficulty focusing and frequently required redirection when interacting with clients. The patient had no concerns other than intermittent mild headaches.
During the next few years, the patient's wife noticed that he became distant with family, was less talkative, and lacked interest in activities that he had previously enjoyed. He made numerous costly errors at work and also had odd behaviors. For example, he entered the kitchen of a local restaurant without permission; on another occasion, he inadvertently borrowed a vehicle from a colleague without first notifying that person. In another instance, while the patient's vehicle was stopped for a routine traffic infraction, he became irritable and briefly evaded police, incurring several legal violations.
One year before this evaluation, the patient was seen in the neurology and psychiatry clinics of another hospital at his wife's request. He had no concerns about his neurocognitive state. He noted that he was sleeping as little as 2 to 3 hours per night but had a good energy level. He reported intermittent mild headaches. He had no sinus pain, numbness, tingling, or constitutional symptoms. On examination, the patient was alert and oriented, with some inattention and confabulation. The remainder of the neurologic examination was normal. A complete blood count and blood levels of electrolytes and glucose were normal, as were results of tests of kidney, liver, and thyroid function. Tests for antinuclear antibodies and for Lyme disease were negative. The patient received diagnoses of attention deficit-hyperactivity disorder, adjustment disorder, and avoidant personality traits. Psychotherapy was initiated, and melatonin and dextroamphetamine-amphetamine were prescribed.
The patient had ongoing personality changes and difficulties with organization and daily functioning, and he was evaluated in the memory disorders clinic of this hospital at his wife's request. She reported that dextroamphetamine-amphetamine had not improved his overall organizational abilities. Although he was physically capable of conducting activities of daily living, he required prompting to perform tasks to maintain basic hygiene, such as bathing. He no longer participated in the management of family finances; he was unable to maintain employment and was receiving disability payments. He had new odd behaviors, such as urinating in public on a few occasions and frequently and unexpectedly visiting family members' workplaces and neighbors' homes at late hours. He also had obsessive behaviors, such as calling his children multiple times to confirm details before a scheduled gathering. The patient was unaware of his inappropriate and unusual behaviors. He did not report having anxiety, depression, or perceptual disturbances.
Approximately 10 years before the current evaluation, the patient had received a diagnosis of Waldenstrom's macroglobulinemia. Because he was asymptomatic, treatment was deferred. Two years before the current evaluation, computed tomography (CT) of the chest, abdomen, and pelvis was performed for disease surveillance. There were multiple enlarged hilar and retrocrural lymph nodes, measuring up to 1.2 cm in greatest dimension, with no evidence of organomegaly or focal osseous lesions. The patient attended routine oncology appointments for disease monitoring. Two months before the current evaluation, a complete blood count and a basic metabolic panel were normal. The blood IgM level was 2850 mg per deciliter (reference range, 40 to 230), and the [beta]2-microglobulin level 2.8 mg liter (reference range, 0 to 2.7); these values had been stable since the diagnosis of Waldenstrom's macroglobulinemia was established.
Other medical history included mitral regurgitation, nephrolithiasis, benign prostatic hyperplasia, bilateral knee osteoarthritis, and spinal stenosis. There was no history of head trauma, stroke, or seizure. Medications included a multivitamin and fish oil; there were no known allergies to medications. The patient did not drink alcohol, smoke tobacco, or use illicit drugs. He lived with his wife, and his daughters and grandchildren lived nearby. He had graduated from high school and trade school before serving in the navy for 2 years; he did not serve in a combat role or have known exposure to toxins. Both of his parents had heart disease, a sister had depression, and a maternal uncle had throat cancer. There was no family history of dementia, neurologic disorders, or psychiatric disorders.
On examination, the patient was well groomed, pleasant, and cooperative. Physical appearance was normal. His Mini-Mental State Examination score was 23 on a scale ranging from 0 to 30 (with higher scores indicating better cognitive function), and his Montreal Cognitive Assessment (MoCA) score was 15 on a scale ranging from 0 to 30 (with higher scores indicating better cognitive function).
Orientation was intact except for an error in recalling the date. On testing of attention, the patient had difficulty with serial sevens calculations and with the digit-span test, in which a sequence of numbers is read by the examiner and repeated by the patient; he repeated only four digits of the forward span correctly. On testing of memory, he repeated five out of five words after two trials and did not spontaneously recall any of the words after 5 minutes; he recalled three of the words when selecting from a written list of word choices. Spontaneous speech production was diminished. On testing of confrontation naming, he identified a camel when shown a picture of a giraffe. On testing of semantic and phonemic fluency, he spontaneously generated six animal names over a 1-minute period, as well as one word that begins with the letter ""F"" over a 1-minute period. The clock-drawing test showed good organization. The letter-number sequencing test (also known as the alternating trail-making test) revealed impaired set shifting, and Luria's three-step test revealed impaired motor sequencing. On testing of verbal abstraction, when the patient was asked to describe how a train and a bicycle are similar, he stated, ""A train is bigger than a bicycle and would crush the bicycle."" Judgment and insight were markedly impaired.
An evaluation of cranial nerve function, sensation, power, bulk, tone, coordination, and gait was normal. Deep-tendon reflexes were normal, and the toes were downgoing bilaterally. Bilateral grasp reflexes and palmomental reflexes were present. Testing for syphilis was negative. The blood folate level was 8.2 ng per milliliter (19 nmol per liter; reference range, >4.7 ng per milliliter [11 nmol per liter]), and the vitamin B12 level 258 pg per milliliter (190 pmol per liter; reference range, >231 pg per milliliter [170 pmol per liter]).
On neuropsychological assessment, social engagement was limited, with a few moments of giggling that was incongruent with the context. Spontaneous speech was fluent but impoverished. There was frequent use of the word ""thing"" to replace lower-frequency words and periodic use of phonemic paraphasias such as ""a fenco type of thing."" Thoughts were coherent but impoverished, tangential, and perseverative. Attention and executive functioning were markedly impaired during assessments of verbal fluency, divided attention, abstract reasoning, and inhibitory control. Visual memory was relatively intact, but verbal memory was impaired in terms of encoding and retrieval. When the patient was asked to describe an image, written language was severely impaired but oral language was relatively intact.
A diagnostic test was reviewed, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Frontotemporal dementia (FTD)\n\nThe patient's symptoms of memory loss, personality changes, and odd behavior, along with his lack of insight into his condition, are indicative of a neurocognitive disorder. His symptoms have been progressive over a period of years, which is consistent with a degenerative brain disease. The patient's difficulties with attention, executive functioning, and verbal memory, along with his relatively intact visual memory, suggest a disorder that primarily affects the frontal and temporal lobes of the brain. His social disinhibition, apathy, and lack of initiative are also characteristic of frontotemporal dementia. The presence of grasp and palmomental reflexes, which are primitive reflexes, further suggest a frontal lobe disorder. The patient's relatively preserved orientation and visual memory, along with his fluent but impoverished spontaneous speech, are more consistent with FTD than with Alzheimer's disease, which typically presents with more pronounced memory impairment and language difficulties. The patient's history of Waldenstrom's macroglobulinemia is unlikely to be related to his neurocognitive symptoms, as this condition typically does not affect the brain.""
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        ""content"": ""The patient's symptoms include memory loss, personality changes, and odd behavior. These symptoms have been ongoing for several years and have progressively worsened. The patient's cognitive function is impaired, as evidenced by his low scores on the Mini-Mental State Examination and the Montreal Cognitive Assessment. His speech is fluent but impoverished, and he has difficulty with attention and executive functioning. He also has impaired verbal memory. These symptoms, along with the patient's age, suggest a neurodegenerative disorder. The patient's history of Waldenstrom's macroglobulinemia is notable, but his blood counts and metabolic panel were normal, suggesting that his cognitive symptoms are not due to this condition. The patient's symptoms do not fit the typical presentation of Alzheimer's disease, which usually involves memory loss as the primary symptom. Instead, his symptoms are more consistent with frontotemporal dementia, which can cause personality changes, odd behavior, and problems with language and executive function.\n\nDiagnosis: Frontotemporal Dementia""
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        ""content"": ""The patient is a 62-year-old man presenting with memory loss, personality changes, and odd behavior. The differential diagnosis for this patient includes Alzheimer's disease, frontotemporal dementia, vascular dementia, and dementia due to a general medical condition such as Waldenstrom's macroglobulinemia. Alzheimer's disease is less likely because the patient's symptoms are not primarily memory loss, and he does not have a family history of Alzheimer's. Vascular dementia is also less likely because the patient does not have a history of stroke or other vascular risk factors. Dementia due to Waldenstrom's macroglobulinemia is possible, but the patient's blood work and CT scans do not show any significant changes in his condition that would suggest it is causing his symptoms. The patient's symptoms of personality changes, odd behavior, and memory loss, along with his neuropsychological assessment showing impaired attention and executive functioning, are most consistent with frontotemporal dementia. This condition often presents with personality changes and odd behavior before memory loss, and it can cause significant impairment in attention and executive functioning. \n\nDiagnosis: Frontotemporal dementia.""
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10.1056/NEJMcpc2027083,Case 40-2020: A 24-Year-Old Man with Headache and Covid-19,"White-cell count (per μl) 400 ,000 8590   7970
Differential count (per μl)
Neutrophils 1800–7000 6470   5940
Lymphocytes   1250   980
Monocytes   730   1050
Hemoglobin (g/dl)   12.7   13.1
Hematocrit (%)   37.8   38.6
Platelet count (per μl)   305,000   353,000
Sodium (mmol/liter)   134   134
Potassium (mmol/liter) 3.6–5.1 3.8   3.4
Chloride (mmol/liter) 98–107 95   93
Carbon dioxide (mmol/liter) 22–32 26   23
Urea nitrogen (mg/dl) 6–20 6   5
Creatinine (mg/dl) 0.6–1.3 0.76   0.74
Glucose (mg/dl) 6 9 113   108
Alanine aminotransferase (U/liter) 10–50 19   32
Aspartate aminotransferase (U/liter) 15–41 27   20
Alkaline phosphatase (U/liter) 32–100 111   117
Total protein (g/dl) 6.1–8.1 8.4 6.3–8.3 8.2
Albumin (g/dl) 3.5–5.2 4.6   4.4
Globulin (g/dl)   3.8   3.8
Creatine kinase (U/liter)   49
Lactate dehydrogenase (U/liter) 11 10 166
Lactic acid (mmol/liter)   1.5
Procalcitonin (ng/ml) 0.00–0.08 0.04
C-reactive protein (mg/liter)  .0 0.7
Erythrocyte sedimentation rate (mm/hr)   22
Ferritin (μg/liter) 2 00 314
d-dimer (ng/ml)   401","Cryptococcal meningoencephalitis and advanced 
human immunodeficiency virus infection.","Cryptococcal meningoencephalitis and advanced 
human immunodeficiency virus infection.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 24-year-old man was admitted to this hospital in the spring of 2020 because of headache and coronavirus disease 2019 (Covid-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient had been in his usual state of health until 3 weeks before this admission, when fatigue, generalized weakness, and headache developed. He also had myalgias, nausea, and vomiting but no fever, cough, or diarrhea. Ibuprofen and aspirin did not alleviate the symptoms.
Two weeks later, headache and weakness persisted and new shortness of breath, pleuritic pain, and anorexia developed. Five days before this admission, the patient sought evaluation at a local urgent care clinic. The temperature was 36.8[degrees]C, and the oxygen saturation 98% while he was breathing ambient air. Physical examination was normal. Laboratory test results are shown in Table 1. A nasopharyngeal swab was obtained to test for SARS-CoV-2 RNA. Intramuscular ketorolac was administered, and the patient was discharged home with recommendations to quarantine.	
Table 1 
The next day, SARS-CoV-2 RNA was detected in the nasopharyngeal swab, and the patient had a telemedicine visit through the urgent care clinic. He reported headache, nausea, anorexia, and weakness. Four days later, the headache worsened, and he had presyncope; he sought evaluation at the emergency department of this hospital.
On arrival at the emergency department, multiple episodes of vomiting occurred. The patient described headache and pain localized behind the eyes, as well as persistent shortness of breath, pleuritic pain, myalgias, nausea, vomiting, and anorexia. There was no fever, cough, abdominal pain, or diarrhea. The patient had undergone an appendectomy during childhood; he reported no other known medical conditions, was taking no medications, and had no known allergies to medications.
The patient was born in Central America and was a university student there when he immigrated to the United States 3 months before admission. He worked in landscaping. He had had heterosexual contacts before immigration and reported that he had used condoms. He did not smoke tobacco or electronic cigarettes, drink alcohol, or use illicit drugs. He lived in an apartment in an urban area of Massachusetts with nine other people, including his brother and sister and their families. The patient did not know his family medical history.
On examination, the temperature was 36.1[degrees]C, the blood pressure 134/90 mm Hg, the heart rate 62 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 21.3. The patient appeared fatigued, diaphoretic, and lethargic. He was intermittently agitated and increasingly somnolent, falling asleep multiple times during a conversation. He frequently squeezed his eyes closed and used his hands to hit his head, stating that it hurt. The pupils were equal and reactive to light; there was no nuchal rigidity. He was alert and oriented and followed commands. Cranial nerve examination was normal, but rotation of the head or lifting of the leg caused pain in the head, eyes, and neck. The lungs were clear. The remainder of the examination was normal.
Results of urinalysis and urine and blood toxicologic screening were normal. Other laboratory test results are shown in Table 1. Chest radiography revealed no opacities. Acetaminophen and intravenous fluids were administered.
Ninety minutes later, the patient was found on the ground next to the stretcher, on his hands and knees, incontinent of urine. Intravenous vancomycin, ceftriaxone, and acyclovir were administered empirically.
Dr. R. Gilberto Gonzalez: Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed no intracranial hemorrhage, mass, or large infarct. There was subtle hypodensity of the basal ganglia. There was posterior flattening of both globes and a partially empty sella turcica. Magnetic resonance imaging (MRI) of the head, performed before and after the administration of intravenous contrast material, revealed posterior flattening of both globes and tapering of the transverse sinuses. T2-weighted images and T2-weighted, fluid-attenuated inversion recovery images showed multiple small hyperintense foci in the caudate nuclei and putamina (Figure 1); several foci appeared to be cystic. In addition, there were scattered hyperintense foci in the subcortical and periventricular white matter of the frontal lobes and the anterior corona radiata.	
Figure 1 
Dr. Shatzman: Lumbar puncture was performed. The opening pressure was higher than 55 cm of water, and the cerebrospinal fluid (CSF) was colorless. On CSF analysis, the total protein level was 47 mg per deciliter (reference range, 5 to 55), and the glucose level 42 mg per deciliter (2.3 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]). There were 108 white cells per microliter (reference range, 0 to 5), of which 81% were lymphocytes and 18% were monocytes.
The patient was admitted to the neurology intensive care unit (ICU) 17 hours after presentation. A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 24-year-old man was admitted to this hospital in the spring of 2020 because of headache and coronavirus disease 2019 (Covid-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient had been in his usual state of health until 3 weeks before this admission, when fatigue, generalized weakness, and headache developed. He also had myalgias, nausea, and vomiting but no fever, cough, or diarrhea. Ibuprofen and aspirin did not alleviate the symptoms.
Two weeks later, headache and weakness persisted and new shortness of breath, pleuritic pain, and anorexia developed. Five days before this admission, the patient sought evaluation at a local urgent care clinic. The temperature was 36.8[degrees]C, and the oxygen saturation 98% while he was breathing ambient air. Physical examination was normal. Laboratory test results are shown in Table 1. A nasopharyngeal swab was obtained to test for SARS-CoV-2 RNA. Intramuscular ketorolac was administered, and the patient was discharged home with recommendations to quarantine.	
Table 1 
The next day, SARS-CoV-2 RNA was detected in the nasopharyngeal swab, and the patient had a telemedicine visit through the urgent care clinic. He reported headache, nausea, anorexia, and weakness. Four days later, the headache worsened, and he had presyncope; he sought evaluation at the emergency department of this hospital.
On arrival at the emergency department, multiple episodes of vomiting occurred. The patient described headache and pain localized behind the eyes, as well as persistent shortness of breath, pleuritic pain, myalgias, nausea, vomiting, and anorexia. There was no fever, cough, abdominal pain, or diarrhea. The patient had undergone an appendectomy during childhood; he reported no other known medical conditions, was taking no medications, and had no known allergies to medications.
The patient was born in Central America and was a university student there when he immigrated to the United States 3 months before admission. He worked in landscaping. He had had heterosexual contacts before immigration and reported that he had used condoms. He did not smoke tobacco or electronic cigarettes, drink alcohol, or use illicit drugs. He lived in an apartment in an urban area of Massachusetts with nine other people, including his brother and sister and their families. The patient did not know his family medical history.
On examination, the temperature was 36.1[degrees]C, the blood pressure 134/90 mm Hg, the heart rate 62 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 21.3. The patient appeared fatigued, diaphoretic, and lethargic. He was intermittently agitated and increasingly somnolent, falling asleep multiple times during a conversation. He frequently squeezed his eyes closed and used his hands to hit his head, stating that it hurt. The pupils were equal and reactive to light; there was no nuchal rigidity. He was alert and oriented and followed commands. Cranial nerve examination was normal, but rotation of the head or lifting of the leg caused pain in the head, eyes, and neck. The lungs were clear. The remainder of the examination was normal.
Results of urinalysis and urine and blood toxicologic screening were normal. Other laboratory test results are shown in Table 1. Chest radiography revealed no opacities. Acetaminophen and intravenous fluids were administered.
Ninety minutes later, the patient was found on the ground next to the stretcher, on his hands and knees, incontinent of urine. Intravenous vancomycin, ceftriaxone, and acyclovir were administered empirically.
Dr. R. Gilberto Gonzalez: Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed no intracranial hemorrhage, mass, or large infarct. There was subtle hypodensity of the basal ganglia. There was posterior flattening of both globes and a partially empty sella turcica. Magnetic resonance imaging (MRI) of the head, performed before and after the administration of intravenous contrast material, revealed posterior flattening of both globes and tapering of the transverse sinuses. T2-weighted images and T2-weighted, fluid-attenuated inversion recovery images showed multiple small hyperintense foci in the caudate nuclei and putamina (Figure 1); several foci appeared to be cystic. In addition, there were scattered hyperintense foci in the subcortical and periventricular white matter of the frontal lobes and the anterior corona radiata.	
Figure 1 
Dr. Shatzman: Lumbar puncture was performed. The opening pressure was higher than 55 cm of water, and the cerebrospinal fluid (CSF) was colorless. On CSF analysis, the total protein level was 47 mg per deciliter (reference range, 5 to 55), and the glucose level 42 mg per deciliter (2.3 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]). There were 108 white cells per microliter (reference range, 0 to 5), of which 81% were lymphocytes and 18% were monocytes.
The patient was admitted to the neurology intensive care unit (ICU) 17 hours after presentation. A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Neurologic manifestation of COVID-19. \n\nThe patient's symptoms of headache, generalized weakness, myalgias, nausea, vomiting, shortness of breath, pleuritic pain, and anorexia, along with the detection of SARS-CoV-2 RNA in a nasopharyngeal swab, confirm the diagnosis of COVID-19. The worsening headache, presyncope, vomiting, and increasing somnolence suggest a neurologic manifestation of the disease. This is further supported by the findings on the CT and MRI scans, which show multiple small hyperintense foci in the caudate nuclei and putamina, and scattered hyperintense foci in the subcortical and periventricular white matter of the frontal lobes and the anterior corona radiata. The lumbar puncture results, showing an elevated opening pressure and an increased number of white cells in the cerebrospinal fluid, also point towards a neurologic involvement.""
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        ""content"": ""This is a young man who presents with headache, generalized weakness, myalgias, nausea, vomiting, shortness of breath, pleuritic pain, and anorexia. He has tested positive for SARS-CoV-2. The differential diagnosis for this patient includes viral meningitis, bacterial meningitis, encephalitis, and COVID-19 associated neurological complications. The patient's symptoms of headache, nausea, vomiting, and anorexia, along with his neurological signs of agitation, somnolence, and pain with head movement, are suggestive of meningitis or encephalitis. His CSF analysis shows lymphocytic predominance, which is more suggestive of viral meningitis or encephalitis than bacterial. However, his imaging shows multiple small hyperintense foci in the caudate nuclei and putamina, as well as scattered hyperintense foci in the subcortical and periventricular white matter of the frontal lobes and the anterior corona radiata. These findings are not typical for viral meningitis or encephalitis, but have been reported in patients with COVID-19. Therefore, the most likely diagnosis is COVID-19 associated neurological complications.\n\nDiagnosis: COVID-19 associated neurological complications.""
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10.1056/NEJMcpc2027078,Case 39-2020: A 29-Month-Old Boy with Seizure and Hypocalcemia,"Sodium (mmol/liter)   140
Potassium (mmol/liter)   4.1
Chloride (mmol/liter)   104
Carbon dioxide (mmol/liter)   20
Anion gap (mmol/liter)   16
Urea nitrogen (mg/dl) 5–20 17
Creatinine (mg/dl) 0.30–1.00 0.25
Glucose (mg/dl)   106
Calcium (mg/dl)   5.6
Ionized calcium (mmol/liter)   0.88
Magnesium (mg/dl)   1.9
Phosphorus (mg/dl) 4.5–5.5 4.3
Alkaline phosphatase (U/liter) 142–335 673
Parathyroid hormone (pg/ml)   177
Urine
Creatinine (mg/dl) Not defined 46
Calcium (mg/dl) Not defined 19.7
Phosphate (mg/dl) Not defined 47.8",Vitamin D deficiency,Vitamin D deficiency,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-month-old boy was transferred to this hospital because of a seizure and hypocalcemia.
Approximately 2 months before the current evaluation, the patient had a febrile seizure associated with an acute viral illness. After the seizure, his mother reported that his ""waddling"" gait had become more pronounced. Two weeks before the current evaluation, the patient was seen in the orthopedic clinic at another hospital. On examination, the cover-up test - in which the distal lower leg is covered and the alignment of the proximal lower leg is compared with that of the upper leg - was negative, a finding consistent with physiologic bowing of the leg. There was a pes planus (flatfoot) deformity that resolved when the patient was not bearing weight on the foot, and there was an external (positive) foot progression angle with ambulation. The mother was counseled that the findings were within the normal range for gait and musculoskeletal development. One day before the current evaluation, the mother noticed that the child's legs ""locked up"" and appeared ""shaky"" when he was walking over a threshold.
On the morning of the current evaluation, the patient's mother noticed that the child was grunting while sleeping, with his eyes rolled upward and his arms stiffened and flexed. After less than 1 minute, the grunting and movements stopped and the patient vomited. Emergency medical services were called, and the patient was transported to the emergency department of another hospital. Vital signs, mental status, and findings on physical examination were reportedly normal. Laboratory evaluation was notable for a blood calcium level of 5.0 mg per deciliter (1.25 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter [2.12 to 2.62 mmol per liter]). Intravenous calcium gluconate was administered. The patient was transferred to the emergency department of this hospital, arriving approximately 18 hours after a presumed seizure.
Further history was obtained from the patient's parents. The patient had been delivered at full term and had reportedly met developmental milestones for his age. His medical history was notable for atopic dermatitis, which had been diagnosed when he was 9 weeks of age, as well as multiple environmental and food allergies. One year earlier, evaluation by an allergist had revealed elevated levels on IgE tests specific to food allergens (milk, cashews, pistachios, egg whites, almonds, soybeans, chickpeas, green peas, lentils, peanuts, and sesame seeds) and environmental allergens (dogs, cats, and dust mites), although the patient later underwent food challenges to peanuts, legumes, almonds, and sesame seeds in an allergy clinic and had no symptoms. There were no known drug allergies. The patient had received diphenhydramine, hydroxyzine, epinephrine, and topical betamethasone as needed. He had not received any routine childhood vaccinations because of his parents' refusal.
The patient lived with his mother, father, two older siblings, and dog in New England. Although the mother was a vegetarian, she occasionally included chicken in the patient's ""natural"" and organic diet. The patient's mother had obsessive-compulsive disorder and anxiety, and his father had oral allergy syndrome and a history of varus knee deformity in childhood. The patient's two siblings had atopic dermatitis, environmental allergies, and food allergies. There was no family history of seizure.
On physical examination, the patient appeared well and was alert and interactive. The temperature was 36.9[degrees]C, the height 83.5 cm (3rd percentile for his age), and the weight 12.4 kg (24th percentile for his age). The blood pressure was 95/63 mm Hg, the pulse 114 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. Muscle spasms occurred in the arms and legs with passive movement. Chvostek's sign (contraction of the facial muscles) was not elicited after tapping on the region of the facial nerve anterior to the external auditory canal; Trousseau's sign (carpal spasm) was not elicited after exertion of pressure from inflation of a sphygmomanometer on the upper arm. Muscle power, bulk, tone, and deep-tendon reflexes were normal, as was the remainder of the examination.
The blood calcium level was 5.6 mg per deciliter (1.40 mmol per liter), the ionized calcium level 0.88 mmol per liter (reference range, 1.14 to 1.30), and the alkaline phosphatase level 673 U per liter (reference range, 142 to 335). Other laboratory test results are shown in Table 1. The patient was admitted to the pediatric intensive care unit.	
Table 1 
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-month-old boy was transferred to this hospital because of a seizure and hypocalcemia.
Approximately 2 months before the current evaluation, the patient had a febrile seizure associated with an acute viral illness. After the seizure, his mother reported that his ""waddling"" gait had become more pronounced. Two weeks before the current evaluation, the patient was seen in the orthopedic clinic at another hospital. On examination, the cover-up test - in which the distal lower leg is covered and the alignment of the proximal lower leg is compared with that of the upper leg - was negative, a finding consistent with physiologic bowing of the leg. There was a pes planus (flatfoot) deformity that resolved when the patient was not bearing weight on the foot, and there was an external (positive) foot progression angle with ambulation. The mother was counseled that the findings were within the normal range for gait and musculoskeletal development. One day before the current evaluation, the mother noticed that the child's legs ""locked up"" and appeared ""shaky"" when he was walking over a threshold.
On the morning of the current evaluation, the patient's mother noticed that the child was grunting while sleeping, with his eyes rolled upward and his arms stiffened and flexed. After less than 1 minute, the grunting and movements stopped and the patient vomited. Emergency medical services were called, and the patient was transported to the emergency department of another hospital. Vital signs, mental status, and findings on physical examination were reportedly normal. Laboratory evaluation was notable for a blood calcium level of 5.0 mg per deciliter (1.25 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter [2.12 to 2.62 mmol per liter]). Intravenous calcium gluconate was administered. The patient was transferred to the emergency department of this hospital, arriving approximately 18 hours after a presumed seizure.
Further history was obtained from the patient's parents. The patient had been delivered at full term and had reportedly met developmental milestones for his age. His medical history was notable for atopic dermatitis, which had been diagnosed when he was 9 weeks of age, as well as multiple environmental and food allergies. One year earlier, evaluation by an allergist had revealed elevated levels on IgE tests specific to food allergens (milk, cashews, pistachios, egg whites, almonds, soybeans, chickpeas, green peas, lentils, peanuts, and sesame seeds) and environmental allergens (dogs, cats, and dust mites), although the patient later underwent food challenges to peanuts, legumes, almonds, and sesame seeds in an allergy clinic and had no symptoms. There were no known drug allergies. The patient had received diphenhydramine, hydroxyzine, epinephrine, and topical betamethasone as needed. He had not received any routine childhood vaccinations because of his parents' refusal.
The patient lived with his mother, father, two older siblings, and dog in New England. Although the mother was a vegetarian, she occasionally included chicken in the patient's ""natural"" and organic diet. The patient's mother had obsessive-compulsive disorder and anxiety, and his father had oral allergy syndrome and a history of varus knee deformity in childhood. The patient's two siblings had atopic dermatitis, environmental allergies, and food allergies. There was no family history of seizure.
On physical examination, the patient appeared well and was alert and interactive. The temperature was 36.9[degrees]C, the height 83.5 cm (3rd percentile for his age), and the weight 12.4 kg (24th percentile for his age). The blood pressure was 95/63 mm Hg, the pulse 114 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. Muscle spasms occurred in the arms and legs with passive movement. Chvostek's sign (contraction of the facial muscles) was not elicited after tapping on the region of the facial nerve anterior to the external auditory canal; Trousseau's sign (carpal spasm) was not elicited after exertion of pressure from inflation of a sphygmomanometer on the upper arm. Muscle power, bulk, tone, and deep-tendon reflexes were normal, as was the remainder of the examination.
The blood calcium level was 5.6 mg per deciliter (1.40 mmol per liter), the ionized calcium level 0.88 mmol per liter (reference range, 1.14 to 1.30), and the alkaline phosphatase level 673 U per liter (reference range, 142 to 335). Other laboratory test results are shown in Table 1. The patient was admitted to the pediatric intensive care unit.	
Table 1 
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Vitamin D Deficiency Rickets\n\nThe patient's symptoms of hypocalcemia, seizures, and a waddling gait are indicative of a metabolic bone disease. The elevated alkaline phosphatase level is a marker of increased bone turnover, which is seen in conditions such as rickets. The patient's diet, described as \""natural\"" and organic, with the mother being a vegetarian, raises the possibility of nutritional deficiencies. The lack of routine childhood vaccinations due to parental refusal also suggests a potential for other health maintenance aspects, such as nutrition, to be non-standard. Given these factors, the most likely diagnosis is Vitamin D Deficiency Rickets.""
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        ""content"": ""The patient's symptoms include a seizure, hypocalcemia, and a waddling gait. The seizure and hypocalcemia could be related, as low calcium levels can cause seizures. The waddling gait could be a sign of a musculoskeletal issue. The patient also has a history of atopic dermatitis and multiple food and environmental allergies, which could indicate an immune system issue. The patient's diet is also mostly vegetarian, which could lead to nutritional deficiencies. The patient's blood calcium level is significantly below the normal range, which could be causing his symptoms. The patient's alkaline phosphatase level is also elevated, which could indicate a bone disorder. Given these findings, the most likely diagnosis is nutritional rickets due to a vitamin D deficiency. This would explain the patient's hypocalcemia, seizure, and waddling gait, as vitamin D is necessary for calcium absorption and bone health.\n\nDiagnosis: Nutritional rickets due to vitamin D deficiency.""
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        ""content"": ""The patient is a young boy who presents with a seizure and hypocalcemia. He also has a history of atopic dermatitis and multiple food and environmental allergies. The differential diagnosis for this patient includes hypoparathyroidism, vitamin D deficiency, malabsorption syndromes, and nutritional deficiencies. The patient's history of atopic dermatitis and multiple allergies raises the possibility of a malabsorption syndrome, but his growth parameters are within normal limits, making this less likely. The patient's diet is described as \""natural\"" and organic, and his mother is a vegetarian, raising the possibility of a nutritional deficiency. However, the patient's diet reportedly includes chicken, making a purely nutritional cause of hypocalcemia less likely. The patient's seizure and hypocalcemia, in the absence of other clear causes, raise the possibility of hypoparathyroidism. The patient's normal growth and development, as well as the absence of other signs of malnutrition, make a primary parathyroid disorder more likely than a nutritional or malabsorption syndrome. The patient's elevated alkaline phosphatase level also suggests a bone disorder, which could be seen in hypoparathyroidism as the body attempts to maintain calcium levels by breaking down bone. \n\nDiagnosis: Hypoparathyroidism.""
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10.1056/NEJMcpc2004991,Case 38-2020: A 52-Year-Old Man with Cancer and Acute Hypoxemia,"Hematocrit (%)   37.5 36.9 30.8 28.8
Hemoglobin (g/dl)   12.2 12.1 10.1 9.7
White-cell count (per μl)   10,910 13,920 10,530 11,750
Differential count (per μl)
Neutrophils   7321
Lymphocytes   1790
Monocytes   1320
Eosinophils   44
Basophils  00 76
Immature granulocytes 0–100 360
Sodium (mmol/liter)   140 143 142 142
Potassium (mmol/liter)   4.0 4.0 3.7 4.0
Chloride (mmol/liter)   96 102 104 106
Carbon dioxide (mmol/liter)   35 27 28 26
Urea nitrogen (mg/dl)   18 27 43 52
Creatinine (mg/dl)   1.34 1.98 2.38 2.13
Glucose (mg/dl)   119 119 123 132
Calcium (mg/dl)   19.7 15.3 13.4 11.5
Ionized calcium (mmol/liter)   1.97 1.75 1.57
Phosphorus (mg/dl)   5.4 4.1 2.7 2.4
25-Hydroxyvitamin D (ng/ml) 2 0 11
Parathyroid hormone, intact (pg/ml)   10
Parathyroid hormone–related peptide 
(pmol/liter)
<2.0 1.0
β2-microglobulin (μg/ml) 0.8 .34 4.40
Uric acid (mg/dl) 3.6–8.5 11.9
d-dimer (ng/ml)   2895
Arterial blood gas analysis
Fraction of inspired oxygen 1.0
pH   7.42
Partial pressure of carbon dioxide (mm Hg)   40
Partial pressure of oxygen (mm Hg)   200","Rasburicase-induced methemoglobinemia in the 
context of glucose-6-phosphate dehydrogenase 
deficiency.
IgA lambda multiple myeloma",Rasburicase-induced methemoglobinemia in the context of glucose-6-phosphate dehydrogenase deficiency.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 52-year-old man was urgently evaluated because of hypoxemia that occurred on the fifth day he was at this hospital for suspected cancer.
The patient had been in his usual state of health until 2 months before presentation to this hospital, when pain on the right side of the back developed. The pain began gradually after the patient had moved heavy furniture, worsened with activity and coughing, sometimes radiated down the back of the right arm to the elbow, and occasionally awakened him from sleep. During the next 2 months, the pain waxed and waned. Ice, ibuprofen, naproxen, cyclobenzaprine, and physical therapy were prescribed but did not lead to any improvement.
One day before presentation to this hospital, the patient was seen in his primary care clinic because the severity of the back pain had increased and numbness and weakness of the right hand had developed. Radiography of the cervical and thoracic spine revealed spondylolisthesis, degenerative changes, and an anterior wedge deformity of the T9 vertebral body of indeterminate duration. The following day, after the imaging results were reviewed, the patient was referred to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported severe, sharp, burning pain in the right shoulder, triceps, and upper and middle back. He also noted fatigue and increased urinary frequency. He had hypertension, dyslipidemia, obesity, and hyperthyroidism. Medications included amlodipine, metoprolol, topiramate, ranitidine, ibuprofen, and naproxen. Peanuts and latex had caused urticaria. Multiple relatives had hypertension and diabetes mellitus. The patient worked in security and did not use alcohol, tobacco, or illicit substances. He identified as Black and as a Jehovah's Witness; he stated that receiving blood transfusions was incompatible with his beliefs.
On examination, the temperature was 37.1[degrees]C, the heart rate 95 beats per minute, the blood pressure 162/88 mm Hg, the respiratory rate 19 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The paraspinal muscles were tender, more so on the right side than on the left side. Strength was 4 out of 5 when the patient extended his right shoulder and when he gripped the examiner's fingers with his right hand. Straight leg raising was normal bilaterally. Oral acetaminophen, ibuprofen, oxycodone, and diazepam and transdermal lidocaine were administered, and the patient was observed overnight in the emergency department. The next morning, the pain persisted; magnetic resonance imaging (MRI) was performed.
Dr. F. Joseph Simeone: MRI of the spine (Figure 1A, 1B, and 1C), performed before and after the administration of intravenous gadolinium, revealed an enhancing, marrow-replacing mass involving the right posterior aspect of the T1 vertebral body, with resultant severe stenosis of the spinal canal and right neural foramen. The bone marrow signal was diffusely heterogeneous, and there were mild compression deformities of multiple thoracic vertebral bodies, including T9, as seen on radiography.	
Figure 1 
Dr. Allison: The blood calcium level was 19.7 mg per deciliter (4.92 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter [2.12 to 2.62 mmol per liter]). The anion gap, platelet count, erythrocyte sedimentation rate, and urinalysis were normal, as were blood levels of magnesium, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, total protein, albumin, globulin, lactate dehydrogenase, thyrotropin, and prostate-specific antigen; other laboratory test results are shown in Table 1. Serum and urine samples were obtained for protein electrophoresis and immunofixation, and another serum sample was obtained to be analyzed for kappa and lambda free light chains. Additional imaging studies were obtained.	
Table 1
Dr. Simeone: Computed tomography (CT) of the chest, abdomen, and pelvis (Figure 1D), performed after the administration of intravenous contrast material, confirmed the lytic lesion at T1 and the compression deformities of multiple thoracic vertebral bodies. Multiple small osteolytic skeletal lesions were identified. There was no evidence of other mass lesions or lymphadenopathy.
Dr. Allison: The patient was admitted to the hospital on the second hospital day; a diagnosis of cancer was suspected. On examination, he appeared fatigued and uncomfortable and had a flat affect. There was diminished sensation of the pads of the second and third fingers on the right hand; the remainder of the examination was unchanged. Oral acetaminophen, subcutaneous calcitonin, and intravenous lactated Ringer's solution, hydromorphone, diazepam, and zoledronic acid were administered. Overnight, the patient became increasingly somnolent, and the oxygen saturation decreased to 91%.
The following morning, on the third hospital day, auscultation of the lungs revealed bibasilar crackles. Laboratory test results are shown in Table 1. Supplemental oxygen was administered through a nasal cannula at a rate of 2 liters per minute, and the oxygen saturation increased to 94%. Lactated Ringer's solution and zoledronic acid were stopped, and intravenous normal saline, furosemide, and dexamethasone were begun.
On the fourth hospital day, a CT-guided bone marrow biopsy was performed. Afterward, trace edema in the legs was noted. Examination of the urinary sediment revealed barrel-shaped crystals, and a 24-hour urine sample contained more than 5 g of protein; other laboratory test results are shown in Table 1. A stool sample was guaiac-negative. Oral cholecalciferol and intravenous rasburicase were administered.
Early the following morning, on the fifth hospital day, the oxygen saturation decreased to 86%, without shortness of breath. The rate of supplemental oxygen administration was increased to 6 liters per minute, but the oxygen saturation did not increase. The temperature was 37.2[degrees]C, the heart rate 81 beats per minute, the blood pressure 126/75 mm Hg, and the respiratory rate 18 breaths per minute. Auscultation of the heart and lungs was normal. Furosemide was administered intravenously, and chest radiography was performed.
Dr. Simeone: An anteroposterior radiograph of the chest showed low lung volumes and otherwise clear lungs (Figure 1E).
Dr. Allison: Two hours later, high-flow oxygen therapy was administered through a nasal cannula (rate, 60 liters per minute; fraction of inspired oxygen [FIO2], 1.0); the oxygen saturation remained unchanged. Blood levels of lactate, troponin T, and N-terminal pro-B-type natriuretic peptide were normal; other laboratory test results are shown in Table 1.
A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 52-year-old man was urgently evaluated because of hypoxemia that occurred on the fifth day he was at this hospital for suspected cancer.
The patient had been in his usual state of health until 2 months before presentation to this hospital, when pain on the right side of the back developed. The pain began gradually after the patient had moved heavy furniture, worsened with activity and coughing, sometimes radiated down the back of the right arm to the elbow, and occasionally awakened him from sleep. During the next 2 months, the pain waxed and waned. Ice, ibuprofen, naproxen, cyclobenzaprine, and physical therapy were prescribed but did not lead to any improvement.
One day before presentation to this hospital, the patient was seen in his primary care clinic because the severity of the back pain had increased and numbness and weakness of the right hand had developed. Radiography of the cervical and thoracic spine revealed spondylolisthesis, degenerative changes, and an anterior wedge deformity of the T9 vertebral body of indeterminate duration. The following day, after the imaging results were reviewed, the patient was referred to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported severe, sharp, burning pain in the right shoulder, triceps, and upper and middle back. He also noted fatigue and increased urinary frequency. He had hypertension, dyslipidemia, obesity, and hyperthyroidism. Medications included amlodipine, metoprolol, topiramate, ranitidine, ibuprofen, and naproxen. Peanuts and latex had caused urticaria. Multiple relatives had hypertension and diabetes mellitus. The patient worked in security and did not use alcohol, tobacco, or illicit substances. He identified as Black and as a Jehovah's Witness; he stated that receiving blood transfusions was incompatible with his beliefs.
On examination, the temperature was 37.1[degrees]C, the heart rate 95 beats per minute, the blood pressure 162/88 mm Hg, the respiratory rate 19 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The paraspinal muscles were tender, more so on the right side than on the left side. Strength was 4 out of 5 when the patient extended his right shoulder and when he gripped the examiner's fingers with his right hand. Straight leg raising was normal bilaterally. Oral acetaminophen, ibuprofen, oxycodone, and diazepam and transdermal lidocaine were administered, and the patient was observed overnight in the emergency department. The next morning, the pain persisted; magnetic resonance imaging (MRI) was performed.
Dr. F. Joseph Simeone: MRI of the spine (Figure 1A, 1B, and 1C), performed before and after the administration of intravenous gadolinium, revealed an enhancing, marrow-replacing mass involving the right posterior aspect of the T1 vertebral body, with resultant severe stenosis of the spinal canal and right neural foramen. The bone marrow signal was diffusely heterogeneous, and there were mild compression deformities of multiple thoracic vertebral bodies, including T9, as seen on radiography.	
Figure 1 
Dr. Allison: The blood calcium level was 19.7 mg per deciliter (4.92 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter [2.12 to 2.62 mmol per liter]). The anion gap, platelet count, erythrocyte sedimentation rate, and urinalysis were normal, as were blood levels of magnesium, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, total protein, albumin, globulin, lactate dehydrogenase, thyrotropin, and prostate-specific antigen; other laboratory test results are shown in Table 1. Serum and urine samples were obtained for protein electrophoresis and immunofixation, and another serum sample was obtained to be analyzed for kappa and lambda free light chains. Additional imaging studies were obtained.	
Table 1
Dr. Simeone: Computed tomography (CT) of the chest, abdomen, and pelvis (Figure 1D), performed after the administration of intravenous contrast material, confirmed the lytic lesion at T1 and the compression deformities of multiple thoracic vertebral bodies. Multiple small osteolytic skeletal lesions were identified. There was no evidence of other mass lesions or lymphadenopathy.
Dr. Allison: The patient was admitted to the hospital on the second hospital day; a diagnosis of cancer was suspected. On examination, he appeared fatigued and uncomfortable and had a flat affect. There was diminished sensation of the pads of the second and third fingers on the right hand; the remainder of the examination was unchanged. Oral acetaminophen, subcutaneous calcitonin, and intravenous lactated Ringer's solution, hydromorphone, diazepam, and zoledronic acid were administered. Overnight, the patient became increasingly somnolent, and the oxygen saturation decreased to 91%.
The following morning, on the third hospital day, auscultation of the lungs revealed bibasilar crackles. Laboratory test results are shown in Table 1. Supplemental oxygen was administered through a nasal cannula at a rate of 2 liters per minute, and the oxygen saturation increased to 94%. Lactated Ringer's solution and zoledronic acid were stopped, and intravenous normal saline, furosemide, and dexamethasone were begun.
On the fourth hospital day, a CT-guided bone marrow biopsy was performed. Afterward, trace edema in the legs was noted. Examination of the urinary sediment revealed barrel-shaped crystals, and a 24-hour urine sample contained more than 5 g of protein; other laboratory test results are shown in Table 1. A stool sample was guaiac-negative. Oral cholecalciferol and intravenous rasburicase were administered.
Early the following morning, on the fifth hospital day, the oxygen saturation decreased to 86%, without shortness of breath. The rate of supplemental oxygen administration was increased to 6 liters per minute, but the oxygen saturation did not increase. The temperature was 37.2[degrees]C, the heart rate 81 beats per minute, the blood pressure 126/75 mm Hg, and the respiratory rate 18 breaths per minute. Auscultation of the heart and lungs was normal. Furosemide was administered intravenously, and chest radiography was performed.
Dr. Simeone: An anteroposterior radiograph of the chest showed low lung volumes and otherwise clear lungs (Figure 1E).
Dr. Allison: Two hours later, high-flow oxygen therapy was administered through a nasal cannula (rate, 60 liters per minute; fraction of inspired oxygen [FIO2], 1.0); the oxygen saturation remained unchanged. Blood levels of lactate, troponin T, and N-terminal pro-B-type natriuretic peptide were normal; other laboratory test results are shown in Table 1.
A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 52-year-old man with a history of hypertension, dyslipidemia, obesity, and hyperthyroidism who presents with severe back pain, numbness and weakness of the right hand, fatigue, and increased urinary frequency. Imaging reveals an enhancing, marrow-replacing mass involving the right posterior aspect of the T1 vertebral body, with resultant severe stenosis of the spinal canal and right neural foramen. The bone marrow signal is diffusely heterogeneous, and there are mild compression deformities of multiple thoracic vertebral bodies. CT imaging confirms the lytic lesion at T1 and the compression deformities of multiple thoracic vertebral bodies, and identifies multiple small osteolytic skeletal lesions. There is no evidence of other mass lesions or lymphadenopathy. The patient's blood calcium level is significantly elevated. \n\nThe differential diagnosis for this patient includes metastatic cancer, multiple myeloma, and hyperparathyroidism. The patient's age, the presence of multiple osteolytic lesions, and the elevated calcium level make metastatic cancer a possibility. However, the absence of other mass lesions or lymphadenopathy makes this less likely. Hyperparathyroidism can cause elevated calcium levels and bone lesions, but it would not typically cause a marrow-replacing mass. Multiple myeloma is a cancer of plasma cells that often presents with bone pain, osteolytic lesions, and elevated calcium levels. The presence of a marrow-replacing mass is also consistent with this diagnosis. \n\nGiven the patient's presentation and test results, the most likely diagnosis is multiple myeloma.""
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10.1056/NEJMcpc2004979,Case 37-2020: A 35-Year-Old Man with Lymphadenopathy and Petechiae,"Hemoglobin (g/dl)   11.4
Hematocrit (%)   37.2
Platelet count (per μl)   0
White-cell count (per μl)   5020
Differential count (per μl)
Neutrophils   3480
Lymphocytes   1120
Monocytes   340
Eosinophils   80
Basophils  00 40
Red-cell count (per μl) 4500–5900 5990
Mean corpuscular volume (fl)   62.1
Mean corpuscular hemoglobin (pg) 26. 4.0 19.0
Mean corpuscular hemoglobin concentration (g/dl) 31. 7.0 30.6
Red-cell distribution width (%)   18.0
Prothrombin time (sec)   14.3
Prothrombin-time international normalized ratio   1.1
Activated partial-thromboplastin time (sec) 22. 6.0 27.9
Fibrinogen (mg/dl) 15 0 413
Alanine aminotransferase (U/liter)   33
Aspartate aminotransferase (U/liter)   27
Bilirubin (mg/dl)
Total  1.2
Direct 0.  0.2
Protein (g/dl)
Total 6. .3 8.2
Albumin   4.1
Globulin   4.1
Creatinine (mg/dl)   0.74
Lactate dehydrogenase (U/liter) 11 10 218
Ferritin (μg/liter) 2 00 162
Folate (ng/ml) >4.7 >20.0
Vitamin B12 (pg/ml) >231 526","Necrotizing granulomatous lymphadenitis due to 
Mycobacterium tuberculosis complex.",Tuberculous lymphadenitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 35-year-old man was admitted to this hospital because of lymphadenopathy and thrombocytopenia.
The patient had been well until 4 months before this admission, when painless swelling developed in the groin area bilaterally; there were no other symptoms. Three months before this admission, the patient was evaluated in the primary care clinic of this hospital. He had multiple enlarged inguinal lymph nodes, which were mobile and nontender on palpation; the largest was 3 cm in diameter. The white-cell count was 5460 per microliter (reference range, 4500 to 11,000), the platelet count 168,000 per microliter (reference range, 150,000 to 400,000), and the hemoglobin level 11.4 g per deciliter (reference range, 13.5 to 17.5). An interferon-[gamma]-release assay (IGRA) for Mycobacterium tuberculosis was negative, as was screening for human immunodeficiency virus (HIV) type 1 p24 antigen and HIV type 1 and type 2 antibodies. The patient was referred for a lymph-node biopsy but chose not to pursue it.
Three weeks before this admission, the patient was again evaluated in the primary care clinic of this hospital. The size of the enlarged lymph nodes had not changed, and there were no new symptoms. He was again referred for a biopsy.
Dr. Melissa Krystel-Whittemore: Three days later, a core-needle biopsy of a left inguinal lymph node was performed. Pathological examination of the biopsy specimen (Figure 1) revealed necrotic tissue with fibrosis and lymphohistiocytic inflammation; no definitive lymph-node tissue was present. Staining for acid-fast bacilli, Brown-Hopps staining, and Grocott methenamine-silver staining were negative. No malignant cells were identified.	
Figure 1 
Dr. O'Kelly: Three days before the current admission, a nosebleed developed and resolved spontaneously. The morning of admission, a petechial rash developed on both legs, and the patient presented to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported 3 months of nonproductive cough that had been attributed to gastroesophageal reflux disease. He had no fever, chills, weight loss, night sweats, dyspnea, headache, or palpable masses other than the inguinal lymphadenopathy. He had a history of [beta]-thalassemia trait and deficiencies of vitamin B12 and folate. For the past 15 years, a chronic pruritic rash on the thighs had occurred intermittently. Two months before this admission, he had received a diagnosis of Helicobacter pylori infection and had been treated with amoxicillin, clarithromycin, and omeprazole. Current medications included cyanocobalamin, folate, albuterol, fluticasone nasal spray, and clotrimazole cream. There were no known drug allergies.
The patient worked as a scientist and his research involved mice, but he had no pets. He was married and monogamous with his wife. Eleven years earlier, the patient had moved to an urban area of New England from northeast India, where he was born. He had last traveled to India 6 years earlier; family members had visited 4 years earlier. The patient had also traveled throughout all regions of the United States during the past 11 years. He drank one alcoholic beverage weekly and did not smoke cigarettes or use illicit drugs. The patient's mother had hypertension, and his father had died from valvular heart disease. One of his sisters had received treatment for pulmonary tuberculosis 1 year earlier, and a second sister had latent tuberculosis; a third sister had diabetes.
On examination, the temperature was 36.2[degrees]C, the blood pressure 127/79 mm Hg, the pulse 82 beats per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.4. He appeared well. Purpura, including a hemorrhagic blister 1 cm in diameter, was noted in the oral mucosa. There were diffuse petechiae on the legs and some petechiae on the torso, flanks, and forearms. There were enlarged, nontender inguinal lymph nodes, which were nonmobile and up to 4 cm in diameter on the left side and were mobile on the right side; no other palpable lymphadenopathy was noted.
The platelet count was 0 per microliter (reference range, 150,000 to 400,000). Blood levels of electrolytes and glucose were normal, as were the results of liver- and renal-function tests and urinalysis. Screening for HIV and hepatitis C virus was negative. Other laboratory test results are shown in Table 1. Examination of a peripheral-blood smear showed very few platelets and no platelet clumps. There were target red cells and elliptocytes; the morphologic features of the lymphocytes were normal.	
Table 1 
Dr. Allen P. Heeger: Ultrasonography of the palpable abnormality in the left groin (Figure 2A) revealed a well-circumscribed mass superficial to the iliac vessels, with a thick hyperemic rind and central necrosis. Computed tomography (CT) of the chest, abdomen, and pelvis (Figure 2B, 2C, and 2D), performed after the intravenous administration of contrast material, revealed a conglomerate lymph-node mass, measuring 4.0 cm by 2.1 cm by 3.1 cm, in the superficial left inguinal region, with peripheral enhancement and central hypodensity. There were similar-appearing lymph nodes in the retroperitoneum and the left iliac chain. There was also mediastinal and bilateral hilar lymphadenopathy, with lymph nodes measuring up to 1.4 cm in diameter, as well as a small lymph node in the right minor fissure. The spleen measured 13.5 cm in length (reference range, <12.2 cm). Positron-emission tomography (PET) from the skull base to the thighs (Figure 2E and 2F), performed after the administration of 18F-fluorodeoxyglucose (FDG) tracer, revealed extensive areas of intense FDG uptake in the chest, abdomen, and pelvis, as well as physiologic uptake in the pharyngeal and mandibular areas.	
Figure 2 
Dr. O'Kelly: Prednisone was administered, and the patient was admitted to the hospital. On the second hospital day, prednisone was stopped and intravenous immune globulin (IVIG) was administered. During the next 3 days, the platelet count increased and the petechiae abated. On the sixth hospital day, the platelet count was 83 per microliter.
A diagnostic procedure was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 35-year-old man was admitted to this hospital because of lymphadenopathy and thrombocytopenia.
The patient had been well until 4 months before this admission, when painless swelling developed in the groin area bilaterally; there were no other symptoms. Three months before this admission, the patient was evaluated in the primary care clinic of this hospital. He had multiple enlarged inguinal lymph nodes, which were mobile and nontender on palpation; the largest was 3 cm in diameter. The white-cell count was 5460 per microliter (reference range, 4500 to 11,000), the platelet count 168,000 per microliter (reference range, 150,000 to 400,000), and the hemoglobin level 11.4 g per deciliter (reference range, 13.5 to 17.5). An interferon-[gamma]-release assay (IGRA) for Mycobacterium tuberculosis was negative, as was screening for human immunodeficiency virus (HIV) type 1 p24 antigen and HIV type 1 and type 2 antibodies. The patient was referred for a lymph-node biopsy but chose not to pursue it.
Three weeks before this admission, the patient was again evaluated in the primary care clinic of this hospital. The size of the enlarged lymph nodes had not changed, and there were no new symptoms. He was again referred for a biopsy.
Dr. Melissa Krystel-Whittemore: Three days later, a core-needle biopsy of a left inguinal lymph node was performed. Pathological examination of the biopsy specimen (Figure 1) revealed necrotic tissue with fibrosis and lymphohistiocytic inflammation; no definitive lymph-node tissue was present. Staining for acid-fast bacilli, Brown-Hopps staining, and Grocott methenamine-silver staining were negative. No malignant cells were identified.	
Figure 1 
Dr. O'Kelly: Three days before the current admission, a nosebleed developed and resolved spontaneously. The morning of admission, a petechial rash developed on both legs, and the patient presented to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported 3 months of nonproductive cough that had been attributed to gastroesophageal reflux disease. He had no fever, chills, weight loss, night sweats, dyspnea, headache, or palpable masses other than the inguinal lymphadenopathy. He had a history of [beta]-thalassemia trait and deficiencies of vitamin B12 and folate. For the past 15 years, a chronic pruritic rash on the thighs had occurred intermittently. Two months before this admission, he had received a diagnosis of Helicobacter pylori infection and had been treated with amoxicillin, clarithromycin, and omeprazole. Current medications included cyanocobalamin, folate, albuterol, fluticasone nasal spray, and clotrimazole cream. There were no known drug allergies.
The patient worked as a scientist and his research involved mice, but he had no pets. He was married and monogamous with his wife. Eleven years earlier, the patient had moved to an urban area of New England from northeast India, where he was born. He had last traveled to India 6 years earlier; family members had visited 4 years earlier. The patient had also traveled throughout all regions of the United States during the past 11 years. He drank one alcoholic beverage weekly and did not smoke cigarettes or use illicit drugs. The patient's mother had hypertension, and his father had died from valvular heart disease. One of his sisters had received treatment for pulmonary tuberculosis 1 year earlier, and a second sister had latent tuberculosis; a third sister had diabetes.
On examination, the temperature was 36.2[degrees]C, the blood pressure 127/79 mm Hg, the pulse 82 beats per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.4. He appeared well. Purpura, including a hemorrhagic blister 1 cm in diameter, was noted in the oral mucosa. There were diffuse petechiae on the legs and some petechiae on the torso, flanks, and forearms. There were enlarged, nontender inguinal lymph nodes, which were nonmobile and up to 4 cm in diameter on the left side and were mobile on the right side; no other palpable lymphadenopathy was noted.
The platelet count was 0 per microliter (reference range, 150,000 to 400,000). Blood levels of electrolytes and glucose were normal, as were the results of liver- and renal-function tests and urinalysis. Screening for HIV and hepatitis C virus was negative. Other laboratory test results are shown in Table 1. Examination of a peripheral-blood smear showed very few platelets and no platelet clumps. There were target red cells and elliptocytes; the morphologic features of the lymphocytes were normal.	
Table 1 
Dr. Allen P. Heeger: Ultrasonography of the palpable abnormality in the left groin (Figure 2A) revealed a well-circumscribed mass superficial to the iliac vessels, with a thick hyperemic rind and central necrosis. Computed tomography (CT) of the chest, abdomen, and pelvis (Figure 2B, 2C, and 2D), performed after the intravenous administration of contrast material, revealed a conglomerate lymph-node mass, measuring 4.0 cm by 2.1 cm by 3.1 cm, in the superficial left inguinal region, with peripheral enhancement and central hypodensity. There were similar-appearing lymph nodes in the retroperitoneum and the left iliac chain. There was also mediastinal and bilateral hilar lymphadenopathy, with lymph nodes measuring up to 1.4 cm in diameter, as well as a small lymph node in the right minor fissure. The spleen measured 13.5 cm in length (reference range, <12.2 cm). Positron-emission tomography (PET) from the skull base to the thighs (Figure 2E and 2F), performed after the administration of 18F-fluorodeoxyglucose (FDG) tracer, revealed extensive areas of intense FDG uptake in the chest, abdomen, and pelvis, as well as physiologic uptake in the pharyngeal and mandibular areas.	
Figure 2 
Dr. O'Kelly: Prednisone was administered, and the patient was admitted to the hospital. On the second hospital day, prednisone was stopped and intravenous immune globulin (IVIG) was administered. During the next 3 days, the platelet count increased and the petechiae abated. On the sixth hospital day, the platelet count was 83 per microliter.
A diagnostic procedure was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with lymphadenopathy and thrombocytopenia. The lymphadenopathy is not tender, which is more typical of a malignant process. The patient also has a history of exposure to tuberculosis, which can cause lymphadenopathy, but his IGRA test was negative. The patient's thrombocytopenia is severe, as evidenced by his platelet count of 0 and the presence of petechiae and purpura. The patient's response to IVIG suggests immune thrombocytopenic purpura (ITP), a condition where the immune system destroys platelets. However, the lymphadenopathy and the presence of a mass in the groin area suggest a possible malignancy. The CT scan shows lymphadenopathy in multiple areas and an enlarged spleen, which is suggestive of lymphoma. The PET scan also shows extensive areas of FDG uptake, which is consistent with malignancy. Therefore, the most likely diagnosis is lymphoma with secondary ITP.\n\nDiagnosis: Lymphoma with secondary immune thrombocytopenic purpura.""
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        ""content"": ""The patient is a 35-year-old man presenting with lymphadenopathy and thrombocytopenia. The differential diagnosis for this patient includes lymphoma, leukemia, autoimmune diseases, and infectious diseases such as HIV, tuberculosis, and mononucleosis. The patient's HIV test was negative, ruling out HIV. The patient's IGRA for Mycobacterium tuberculosis was also negative, making tuberculosis less likely. The patient does not have fever, night sweats, or weight loss, which are common symptoms of lymphoma and leukemia, making these diagnoses less likely. The patient does have a history of beta-thalassemia trait and deficiencies of vitamin B12 and folate, which could potentially cause thrombocytopenia. However, the patient's lymphadenopathy and the fact that his platelet count dropped to 0 per microliter suggest a more serious condition. The patient's CT scan revealed a conglomerate lymph-node mass in the superficial left inguinal region, similar-appearing lymph nodes in the retroperitoneum and the left iliac chain, mediastinal and bilateral hilar lymphadenopathy, and a small lymph node in the right minor fissure. The patient's PET scan revealed extensive areas of intense FDG uptake in the chest, abdomen, and pelvis. These findings are consistent with lymphoma. \n\nDiagnosis: Lymphoma.""
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10.1056/NEJMcpc2027077,"Case 36-2020: A 72-Year-Old Woman with Dark Urine and Weakness
","Hemoglobin (g/dl)   12.5 8.5   8.4 7.8
Hematocrit (%)   39.9 26.7   26.5 23.9
Red-cell count (per μl) 4,000,000–5,200,000 3,980,000 2,740,000 4,000,000–5,200,000 2,580,000 2,360,000
White-cell count (per μl)   7300 5800   7790 6840
Mean corpuscular volume (fl)   100.4 97.5   102.7 101.3
Red-cell distribution width (%)   14.6 20.7   20.4 21.2
Platelet count (per μl)   266,000 332,000   353,000 339,000
Alanine aminotransferase (U/liter) 7–40 57   32 28
Aspartate aminotransferase (U/liter) 13–40 135   251 220
Total bilirubin (mg/dl) 0.3–1.2 2.1 0–1.0 2.8 2.2
Direct bilirubin (mg/dl) 0–0.3 0.5   0.3 0.3                                                Creatine kinase (U/liter) 34–145 369
Iron (μg/dl) 50–170 127 30–160 108
Total iron-binding capacity (μg/dl) 250–425 322 23 4 266                       Ferritin (μg/liter) 7.3–270.7 175 1 00 199
C-reactive protein (mg/liter)  .0 <4.0   0.7
Reticulocyte count (%) 0.5–1.5 13.3 0.7–2.5 11.9
Lactate dehydrogenase (U/liter) 12 46 3680 11 10 4028 3426
High-sensitivity troponin T (ng/liter) 0–9 0–9 35
N-terminal pro–B-type natriuretic peptide 
(pg/ml)
<900 <900 662
International normalized ratio   2.12‡ 1.74‡   1.4 1.5
Glycated hemoglobin (%) 4.3–6.4 4.3–6.4 <4.2
Urine
Color Yellow Orange Yellow Brown
Clarity Clear Cloudy Clear Cloudy
pH 5.5–7.5 6.5   6.0
Specific gravity 1.005–1.025 1.015   1.011                                        Bilirubin Negative Negative Negative Negative
Glucose Negative Negative Negative Negative
Ketones Negative Negative Negative Negative
Leukocyte esterase Negative Moderate Negative 1+
Nitrite Negative Negative Negative Negative
Blood Negative Large Negative 2+
Protein Negative 100 mg/dl Negative 2+
Red cells (per high-power field) Negative 5–10   3–5
White cells (per high-power field) Negative 31–35   1 0",Prosthetic paravalvular leak,Acute hemolytic anemia due to a paravalvular leak of a mechanical mitral valve.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 72-year-old woman with a history of rheumatic heart disease was evaluated at this hospital because of weakness and dark urine.
The patient had been in her usual state of health, which included recreational swimming and hiking, until 3 weeks before this admission, when she noted an abrupt onset of dark, rust-colored urine after a trip to Europe. During her trip, she had increased her intake of alcohol. She had no other bleeding symptoms and reported no dysuria, abdominal pain, anorexia, weight change, nausea, emesis, or antecedent trauma; she took no nonsteroidal antiinflammatory drugs (NSAIDs). Dark urine occurred with every instance of urination. She decided on her own to reduce her dose of warfarin, which she had been taking for 25 years after mechanical mitral-valve and aortic-valve replacements, and to take one dose of ciprofloxacin, which had been left over from a previous prescription.
One week later, the patient was evaluated by her primary care physician. Examination was notable for a slightly sallow complexion. The blood levels of electrolytes, glucose, albumin, and alkaline phosphatase were normal, as were the results of renal-function tests. Other laboratory test results are shown in Table 1. Urine dipstick testing was positive for blood, and a urine specimen was obtained for culture.	
Table 1 
Ten days later, the patient reported fatigue with activity, and imaging studies were performed. Computed tomography (CT) of the abdomen and pelvis, performed without the administration of intravenous contrast material, reportedly revealed only a punctate nonobstructing renal stone in the left kidney. Outpatient cystoscopy was reportedly unrevealing.
Four days later, the fatigue increased, and the patient reported feeling ""very weak,"" with exertional dyspnea manifesting as a ""hard time with walking""; her husband noted that she appeared pale, and she presented to her primary care physician for additional evaluation. Examination revealed a systolic murmur and skin pallor. A direct antiglobulin test was negative, the haptoglobin level was undetectable, and the levels of folate and vitamin B12 were normal; other laboratory test results are shown in Table 1. The next day, after the results became available, the patient was evaluated in the emergency department of this hospital.
A review of systems was notable for pale and yellow skin, generalized weakness, and dyspnea on modest exertion. The patient reported that her arms and legs felt heavy, without pain or paresthesia. There was no chest pain or pressure, palpitations, edema, or orthopnea. She reported no bleeding from the oropharynx, nose, vagina, or rectum and no bruising. There were no fevers, chills, night sweats, anorexia, weight loss, respiratory symptoms, gastrointestinal symptoms, or other genitourinary symptoms.
The patient's medical history was notable for dyslipidemia, osteoporosis, resection of breast ductal carcinoma along with axillary lymph-node dissection, and rheumatic fever during adolescence. Two decades after having rheumatic fever, she had severe symptomatic aortic stenosis and mitral stenosis with moderate mitral regurgitation that was complicated by heart failure, exercise intolerance, and pulmonary hypertension; she underwent mechanical bileaflet tilting-disk aortic-valve and mitral-valve replacements 25 years before this admission. Medications included warfarin and atorvastatin. Her warfarin treatment was managed by a local clinic, and her international normalized ratio (INR) was checked approximately every 3 to 4 weeks; historically, her INRs were within the range of 2.0 to 2.5. There were no adverse reactions to either medication. She lived with her husband and was a former teacher. She was active and enjoyed swimming and hiking. She did not smoke or use illicit substances; she drank wine in social settings. There was no family history of cardiac, renal, or hematologic disease.
The temperature was 36.2[degrees]C, the heart rate 96 beats per minute, the blood pressure 144/65 mm Hg, and the oxygen saturation 100% while the patient was breathing ambient air; the body-mass index (the weight in kilograms divided by the square of the height in meters) was 22.9. On examination, she appeared pale and mildly jaundiced but otherwise generally well. Examination of the eyes revealed scleral icterus. There was no evidence of bleeding, petechiae, or ecchymoses in the oropharynx or on the skin. The jugular venous pressure was 10 cm of water. Auscultation revealed crisp metallic S1 and S2 sounds, a crescendo-decrescendo systolic murmur (grade 1/6) at the right upper sternal border, a harsh systolic murmur (grade 3/6) at the apex, and clear lungs. There was no organomegaly or suprapubic tenderness. No enlarged lymph nodes were identified. Distal pulses were intact, the hands and feet were warm, and there was no edema. The remainder of the examination was normal.
The blood levels of electrolytes, glucose, lactate, total protein, albumin, alkaline phosphatase, vitamin B12, and folate were normal, as were the results of tests of renal function; other laboratory test results are shown in Table 1. An electrocardiogram showed sinus rhythm, borderline R-wave progression in the precordial leads, and submillimeter ST-segment depressions in the lateral leads.
Dr. Brian B. Ghoshhajra: An anteroposterior radiograph of the chest (Figure 1A) showed sternal wires, chondrocalcinosis, and clear lungs, as well as enlargement of the left atrium. The valve prostheses were not well visualized.	
Figure 1 
Dr. Haimovich: Point-of-care cardiac ultrasonography that was performed in the emergency department reportedly revealed normal biventricular function, no evidence of pericardial effusion, and a possible clot on the mitral valve. Intravenous heparin was administered, and the patient was admitted to the cardiology inpatient unit.
Dr. Mayooran Namasivayam: On the second day of hospitalization, a transthoracic echocardiogram (Figure 1B and 1C and Video 1, available with the full text of this article at
NEJM.org
) showed nondilated left and right ventricles with normal systolic function and mobile chordae tendineae in the left ventricular cavity consistent with previous mitral-valve replacement. The mechanical aortic prosthesis was well seated with a mean transaortic pressure gradient of 14 mm Hg and with mild regurgitation. The mechanical mitral prosthesis was well seated with extensive perimitral annular calcification that extended to the mitral subvalvular apparatus but did not interfere with the opening and closing of the prosthetic mitral-valve disks, without evidence of thrombosis on the valve. The mean transmitral pressure gradient was 4 mm Hg measured at 80 beats per minute. Mitral regurgitation could not be assessed owing to acoustic reverberation and shadowing. Mild-to-moderate tricuspid regurgitation was present with an estimated right ventricular systolic pressure of 45 mm Hg. There was no echocardiographic evidence of pulmonary-valve disease, ventricular septal defect, left ventricular outflow obstruction, or pericardial effusion. The inferior vena cava was not dilated and collapsed well with inspiration.
Dr. Haimovich: The fibrinogen level was normal, and the haptoglobin level was undetectable. Other laboratory test results are shown in Table 1. The hematology service was consulted; a peripheral-blood smear showed normal red cells with mild central pallor, 1 schistocyte per high-power field with numerous reticulocytes, and normal white cells and platelets.
Additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 72-year-old woman with a history of rheumatic heart disease was evaluated at this hospital because of weakness and dark urine.
The patient had been in her usual state of health, which included recreational swimming and hiking, until 3 weeks before this admission, when she noted an abrupt onset of dark, rust-colored urine after a trip to Europe. During her trip, she had increased her intake of alcohol. She had no other bleeding symptoms and reported no dysuria, abdominal pain, anorexia, weight change, nausea, emesis, or antecedent trauma; she took no nonsteroidal antiinflammatory drugs (NSAIDs). Dark urine occurred with every instance of urination. She decided on her own to reduce her dose of warfarin, which she had been taking for 25 years after mechanical mitral-valve and aortic-valve replacements, and to take one dose of ciprofloxacin, which had been left over from a previous prescription.
One week later, the patient was evaluated by her primary care physician. Examination was notable for a slightly sallow complexion. The blood levels of electrolytes, glucose, albumin, and alkaline phosphatase were normal, as were the results of renal-function tests. Other laboratory test results are shown in Table 1. Urine dipstick testing was positive for blood, and a urine specimen was obtained for culture.	
Table 1 
Ten days later, the patient reported fatigue with activity, and imaging studies were performed. Computed tomography (CT) of the abdomen and pelvis, performed without the administration of intravenous contrast material, reportedly revealed only a punctate nonobstructing renal stone in the left kidney. Outpatient cystoscopy was reportedly unrevealing.
Four days later, the fatigue increased, and the patient reported feeling ""very weak,"" with exertional dyspnea manifesting as a ""hard time with walking""; her husband noted that she appeared pale, and she presented to her primary care physician for additional evaluation. Examination revealed a systolic murmur and skin pallor. A direct antiglobulin test was negative, the haptoglobin level was undetectable, and the levels of folate and vitamin B12 were normal; other laboratory test results are shown in Table 1. The next day, after the results became available, the patient was evaluated in the emergency department of this hospital.
A review of systems was notable for pale and yellow skin, generalized weakness, and dyspnea on modest exertion. The patient reported that her arms and legs felt heavy, without pain or paresthesia. There was no chest pain or pressure, palpitations, edema, or orthopnea. She reported no bleeding from the oropharynx, nose, vagina, or rectum and no bruising. There were no fevers, chills, night sweats, anorexia, weight loss, respiratory symptoms, gastrointestinal symptoms, or other genitourinary symptoms.
The patient's medical history was notable for dyslipidemia, osteoporosis, resection of breast ductal carcinoma along with axillary lymph-node dissection, and rheumatic fever during adolescence. Two decades after having rheumatic fever, she had severe symptomatic aortic stenosis and mitral stenosis with moderate mitral regurgitation that was complicated by heart failure, exercise intolerance, and pulmonary hypertension; she underwent mechanical bileaflet tilting-disk aortic-valve and mitral-valve replacements 25 years before this admission. Medications included warfarin and atorvastatin. Her warfarin treatment was managed by a local clinic, and her international normalized ratio (INR) was checked approximately every 3 to 4 weeks; historically, her INRs were within the range of 2.0 to 2.5. There were no adverse reactions to either medication. She lived with her husband and was a former teacher. She was active and enjoyed swimming and hiking. She did not smoke or use illicit substances; she drank wine in social settings. There was no family history of cardiac, renal, or hematologic disease.
The temperature was 36.2[degrees]C, the heart rate 96 beats per minute, the blood pressure 144/65 mm Hg, and the oxygen saturation 100% while the patient was breathing ambient air; the body-mass index (the weight in kilograms divided by the square of the height in meters) was 22.9. On examination, she appeared pale and mildly jaundiced but otherwise generally well. Examination of the eyes revealed scleral icterus. There was no evidence of bleeding, petechiae, or ecchymoses in the oropharynx or on the skin. The jugular venous pressure was 10 cm of water. Auscultation revealed crisp metallic S1 and S2 sounds, a crescendo-decrescendo systolic murmur (grade 1/6) at the right upper sternal border, a harsh systolic murmur (grade 3/6) at the apex, and clear lungs. There was no organomegaly or suprapubic tenderness. No enlarged lymph nodes were identified. Distal pulses were intact, the hands and feet were warm, and there was no edema. The remainder of the examination was normal.
The blood levels of electrolytes, glucose, lactate, total protein, albumin, alkaline phosphatase, vitamin B12, and folate were normal, as were the results of tests of renal function; other laboratory test results are shown in Table 1. An electrocardiogram showed sinus rhythm, borderline R-wave progression in the precordial leads, and submillimeter ST-segment depressions in the lateral leads.
Dr. Brian B. Ghoshhajra: An anteroposterior radiograph of the chest (Figure 1A) showed sternal wires, chondrocalcinosis, and clear lungs, as well as enlargement of the left atrium. The valve prostheses were not well visualized.	
Figure 1 
Dr. Haimovich: Point-of-care cardiac ultrasonography that was performed in the emergency department reportedly revealed normal biventricular function, no evidence of pericardial effusion, and a possible clot on the mitral valve. Intravenous heparin was administered, and the patient was admitted to the cardiology inpatient unit.
Dr. Mayooran Namasivayam: On the second day of hospitalization, a transthoracic echocardiogram (Figure 1B and 1C and Video 1, available with the full text of this article at
NEJM.org
) showed nondilated left and right ventricles with normal systolic function and mobile chordae tendineae in the left ventricular cavity consistent with previous mitral-valve replacement. The mechanical aortic prosthesis was well seated with a mean transaortic pressure gradient of 14 mm Hg and with mild regurgitation. The mechanical mitral prosthesis was well seated with extensive perimitral annular calcification that extended to the mitral subvalvular apparatus but did not interfere with the opening and closing of the prosthetic mitral-valve disks, without evidence of thrombosis on the valve. The mean transmitral pressure gradient was 4 mm Hg measured at 80 beats per minute. Mitral regurgitation could not be assessed owing to acoustic reverberation and shadowing. Mild-to-moderate tricuspid regurgitation was present with an estimated right ventricular systolic pressure of 45 mm Hg. There was no echocardiographic evidence of pulmonary-valve disease, ventricular septal defect, left ventricular outflow obstruction, or pericardial effusion. The inferior vena cava was not dilated and collapsed well with inspiration.
Dr. Haimovich: The fibrinogen level was normal, and the haptoglobin level was undetectable. Other laboratory test results are shown in Table 1. The hematology service was consulted; a peripheral-blood smear showed normal red cells with mild central pallor, 1 schistocyte per high-power field with numerous reticulocytes, and normal white cells and platelets.
Additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 72-year-old woman with a history of rheumatic heart disease, mechanical mitral-valve and aortic-valve replacements, and long-term warfarin use. She presents with dark, rust-colored urine, fatigue, weakness, exertional dyspnea, and pallor. The patient's symptoms and lab results suggest hemolytic anemia. The differential diagnosis includes mechanical hemolysis due to the artificial heart valves, warfarin-related bleeding, and autoimmune hemolytic anemia. The patient's urine is positive for blood, but imaging studies and cystoscopy do not reveal a source of bleeding. The patient's INR is within the therapeutic range, making warfarin-related bleeding less likely. The direct antiglobulin test is negative, which makes autoimmune hemolytic anemia less likely. The patient's symptoms began after a trip to Europe and increased alcohol intake, but she does not have symptoms of an infection or liver disease. The peripheral-blood smear shows 1 schistocyte per high-power field with numerous reticulocytes, which is consistent with mechanical hemolysis. The patient's mechanical heart valves could cause mechanical destruction of red blood cells, leading to hemolytic anemia. \n\nDiagnosis: Mechanical hemolysis due to artificial heart valves.""
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}",Mechanical hemolysis due to artificial heart valves,Y
10.1056/NEJMcpc2002412,"Case 35-2020: A 59-Year-Old Woman with Type 1 Diabetes Mellitus and Obtundation
C","Hemoglobin (g/dl)   14.0   12.1
Hematocrit (%)   43.9   39.1
White-cell count (per μl) 4500 –11,000 22,600   10,490
Differential count (per μl)
Neutrophils   140,017   82,954
Lymphocytes   17,441   25,606
Monocytes   4727   8260
Eosinophils   326   236
Basophils  00 489  00 354
Platelet count (per μl)   163,000   118,000
Mean corpuscular volume (fl)   88.3   89.3
Creatine kinase (U/liter) 38–174 518   379
C-reactive protein (mg/liter)  .0 42.8
Glucose (mg/dl) 70–100 321   229
Beta hydroxybutyrate (mmol/liter) 0.02–0.27 0.97
Ferritin (μg/liter) 1 00 1,381
Iron (μg/dl) 30–160 20
Total iron-binding capacity (μg/dl) 23 4 127
Cerebrospinal fluid
Color Colorless Yellow Colorless Yellow
Xanthochromia Absent Present None None
White-cell count (per μl) 0–10 18 0–5 2
Differential count (per μl)
Neutrophils   10.8 0 0
Lymphocytes 4 0 2.34 0–5 1.36
Monocytes 0–45 5.04 0–5 0.64
Red-cell count (per μl) 0 165 0–5 156
Protein (mg/dl) 15–50 115 5–55 105
Glucose (mg/dl) 4 0 178 50–75 134","Aceruloplasminemia, hereditary",Aceruloplasminemia,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 59-year-old woman with type 1 diabetes mellitus was transferred to the neurology intensive care unit (ICU) of this hospital in the winter because of obtundation.
The evening before this presentation, the patient was observed by her neighbor to be sitting in the driver's seat of a vehicle in her driveway. The following morning, she remained seated in the same position and was found to be unresponsive; the neighbor attempted to wake her but could not. On arrival of emergency medical services personnel, intranasal naloxone was administered but did not have any effect on her mental status. The patient was transported to the emergency department of another hospital for evaluation.
On arrival at the emergency department, the patient was unable to provide any history. She did not open her eyes but moaned in response to tactile stimulation and withdrew her arms and legs in response to noxious stimulation. The pupils were 4 mm in diameter and reactive to light. Corneal, oculocephalic, and gag reflexes were present. Reflexes were 2+ and symmetric in the arms and absent in the legs; the Babinski sign was present bilaterally. A pump for continuous subcutaneous insulin infusion was in place. The remainder of the examination was normal.
The blood glucose level was 321 mg per deciliter (17.8 mmol per liter; reference range, 70 to 100 mg per deciliter [3.9 to 5.6 mmol per liter]). Blood levels of electrolytes, calcium, albumin, lactate, ammonia, troponin, thyrotropin, carboxyhemoglobin, and methemoglobin were normal, as were results of renal-function and liver-function tests; other laboratory test results are shown in Table 1. Urinalysis revealed a specific gravity of more than 1.030 and the presence of protein, glucose, and ketones. Urine and blood toxicologic screening was negative. The insulin pump was interrogated, and there had been no hypoglycemic episodes in the preceding week. Specimens of blood were obtained for culture.	
Table 1 
Dr. Otto Rapalino: Computed tomography (CT) of the head, performed without the intravenous administration of contrast material, revealed subtle, symmetric increased attenuation in the basal ganglia, thalami, and dentate nuclei. Magnetic resonance imaging (MRI) of the head revealed extensive signal loss in the basal ganglia, thalami, dentate nuclei, and leptomeningeal surfaces on gradient echo images.
Dr. Balaban: A lumbar puncture was performed; results of cerebrospinal fluid (CSF) analysis are shown in Table 1. Gram's staining of the CSF showed rare neutrophils with no organisms. Cultures were performed. Tests of the CSF for herpes simplex virus types 1 and 2 DNA and syphilis were negative, as was examination of a smear for acid-fast bacilli. Cytologic studies of the CSF showed rare atypical cells.
Electroencephalography showed generalized slowing without epileptiform activity. Vancomycin, ceftriaxone, and acyclovir were administered. During the next 2 days, the patient's mental status did not improve. Cultures of blood and CSF obtained 48 hours previously showed no growth. The patient was transferred by ambulance to the neurology ICU of this hospital for further evaluation.
On arrival at this hospital, the patient was unable to answer questions, and additional history was obtained from her medical records. A diagnosis of type 1 diabetes mellitus had been made when she was 19 years of age, and the disease had been complicated by diabetic retinopathy. Other medical history included chronic lymphocytic leukemia, ductal carcinoma in situ of the breast (for which she had undergone lumpectomy), chronic anemia, asthma, and arthritis due to Lyme disease. Medications included rituximab administered every 3 months for the treatment of chronic lymphocytic leukemia, subcutaneous insulin infusion, and inhaled budesonide and albuterol; letrozole had been prescribed, but the patient had not taken the medication for the preceding 3 months. The patient had allergies to penicillin, cephalexin, and ciprofloxacin. She lived with her adult daughter in a suburban community in New England; her husband had died of renal cell carcinoma 4 years earlier. She did not smoke tobacco, drink alcohol, or use illicit substances. Her mother had had a history of hypertension and essential thrombocytosis, and her father had had type 2 diabetes mellitus. A maternal aunt had died of breast cancer at an unknown age, and another maternal aunt had had ovarian cancer.
On examination, the patient opened her eyes and moaned in response to sternal rub and showed purposeful movement toward changing painful stimuli. Her pupils were 4 mm and reactive to light. She blinked appropriately in response to confrontational threat in all fields. The oculocephalic reflex was present, and her face appeared symmetric. The remainder of the evaluation was normal.
Blood levels of cobalamin and cortisol were normal; additional laboratory test results are shown in Table 1. On a repeat lumbar puncture, the opening pressure was 14 cm of water; other results are shown in Table 1. Tests of the CSF for Lyme disease and for enterovirus, varicella virus, and West Nile virus infection were performed.
Dr. Rapalino: Repeat MRI of the head confirmed the presence of diffuse, symmetric hypointensity on T2-weighted images and showed abnormal susceptibility signal throughout the basal ganglia, thalami, dentate nuclei, and cortical surfaces of the cerebral hemispheres on susceptibility-weighted images (Figure 1).	
Figure 1 
Dr. Balaban: Electroencephalography showed generalized polymorphic theta slowing in the background and frequent, prolonged runs of bifrontal irregular delta activity with embedded bifrontal low-amplitude blunt discharges.
Vancomycin, ceftriaxone, and acyclovir were continued, and meropenem was administered intravenously. During the next 3 days, the patient began to open her eyes spontaneously, move her arms and legs independently, and follow commands intermittently. Increased tone was noted in the legs and arms. Cultures of blood and CSF obtained 72 hours previously showed no growth. The CSF tests for Lyme disease and for enterovirus, varicella virus, and West Nile virus infection were negative. Vancomycin, ceftriaxone, and acyclovir were discontinued, and the patient was transferred from the ICU to the neurology unit.
Additional history was obtained from the patient's neighbors, outpatient endocrinologist, and family. Two years before this presentation, the patient's neighbors had noted the development of suspicious and paranoid beliefs. For example, the patient believed that her computer was being used to spy on her and gather personal information, and she repeatedly asked them to help fix the device.
Approximately 21 months before this presentation, the patient's endocrinologist had noted the development of confusion. The patient began to contact her physician's office repeatedly, often several times daily. Whereas she had previously managed her diabetes with a high degree of sophistication, she began to ask questions that suggested she was having difficulty with basic diabetes management. Her telephone calls contained many unrelated and, at times, nonsensical questions; emails were similarly tangential and incoherent. When she was asked about these changes, the patient reported that her cognitive function was as ""sharp as a tack"" and that her emails were confusing because of ""slow Internet speed."" During an office visit with her endocrinologist, the Mini-Mental State Examination (MMSE) score was 24 on a scale ranging from 0 to 30, with higher scores indicating better cognitive function; points were deducted because the patient had made errors of short-term object recall, attention, and calculation. The patient was referred to the outpatient neurology clinic of the other hospital for further evaluation, but she did not attend the scheduled visit.
Two weeks before the current presentation, the patient's family had noted that she had sent individualized holiday gifts to incorrect family members. In the accompanying holiday cards, her penmanship, which had previously been neat, was nearly illegible and was likened by family members to a child's handwriting.
During the current hospitalization, the patient continued to show slow neurologic improvement with supportive care. She was able to answer questions in short sentences, was oriented to self but not to time or place, and was unable to provide further history about the events that led to her hospitalization. A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 59-year-old woman with type 1 diabetes mellitus was transferred to the neurology intensive care unit (ICU) of this hospital in the winter because of obtundation.
The evening before this presentation, the patient was observed by her neighbor to be sitting in the driver's seat of a vehicle in her driveway. The following morning, she remained seated in the same position and was found to be unresponsive; the neighbor attempted to wake her but could not. On arrival of emergency medical services personnel, intranasal naloxone was administered but did not have any effect on her mental status. The patient was transported to the emergency department of another hospital for evaluation.
On arrival at the emergency department, the patient was unable to provide any history. She did not open her eyes but moaned in response to tactile stimulation and withdrew her arms and legs in response to noxious stimulation. The pupils were 4 mm in diameter and reactive to light. Corneal, oculocephalic, and gag reflexes were present. Reflexes were 2+ and symmetric in the arms and absent in the legs; the Babinski sign was present bilaterally. A pump for continuous subcutaneous insulin infusion was in place. The remainder of the examination was normal.
The blood glucose level was 321 mg per deciliter (17.8 mmol per liter; reference range, 70 to 100 mg per deciliter [3.9 to 5.6 mmol per liter]). Blood levels of electrolytes, calcium, albumin, lactate, ammonia, troponin, thyrotropin, carboxyhemoglobin, and methemoglobin were normal, as were results of renal-function and liver-function tests; other laboratory test results are shown in Table 1. Urinalysis revealed a specific gravity of more than 1.030 and the presence of protein, glucose, and ketones. Urine and blood toxicologic screening was negative. The insulin pump was interrogated, and there had been no hypoglycemic episodes in the preceding week. Specimens of blood were obtained for culture.	
Table 1 
Dr. Otto Rapalino: Computed tomography (CT) of the head, performed without the intravenous administration of contrast material, revealed subtle, symmetric increased attenuation in the basal ganglia, thalami, and dentate nuclei. Magnetic resonance imaging (MRI) of the head revealed extensive signal loss in the basal ganglia, thalami, dentate nuclei, and leptomeningeal surfaces on gradient echo images.
Dr. Balaban: A lumbar puncture was performed; results of cerebrospinal fluid (CSF) analysis are shown in Table 1. Gram's staining of the CSF showed rare neutrophils with no organisms. Cultures were performed. Tests of the CSF for herpes simplex virus types 1 and 2 DNA and syphilis were negative, as was examination of a smear for acid-fast bacilli. Cytologic studies of the CSF showed rare atypical cells.
Electroencephalography showed generalized slowing without epileptiform activity. Vancomycin, ceftriaxone, and acyclovir were administered. During the next 2 days, the patient's mental status did not improve. Cultures of blood and CSF obtained 48 hours previously showed no growth. The patient was transferred by ambulance to the neurology ICU of this hospital for further evaluation.
On arrival at this hospital, the patient was unable to answer questions, and additional history was obtained from her medical records. A diagnosis of type 1 diabetes mellitus had been made when she was 19 years of age, and the disease had been complicated by diabetic retinopathy. Other medical history included chronic lymphocytic leukemia, ductal carcinoma in situ of the breast (for which she had undergone lumpectomy), chronic anemia, asthma, and arthritis due to Lyme disease. Medications included rituximab administered every 3 months for the treatment of chronic lymphocytic leukemia, subcutaneous insulin infusion, and inhaled budesonide and albuterol; letrozole had been prescribed, but the patient had not taken the medication for the preceding 3 months. The patient had allergies to penicillin, cephalexin, and ciprofloxacin. She lived with her adult daughter in a suburban community in New England; her husband had died of renal cell carcinoma 4 years earlier. She did not smoke tobacco, drink alcohol, or use illicit substances. Her mother had had a history of hypertension and essential thrombocytosis, and her father had had type 2 diabetes mellitus. A maternal aunt had died of breast cancer at an unknown age, and another maternal aunt had had ovarian cancer.
On examination, the patient opened her eyes and moaned in response to sternal rub and showed purposeful movement toward changing painful stimuli. Her pupils were 4 mm and reactive to light. She blinked appropriately in response to confrontational threat in all fields. The oculocephalic reflex was present, and her face appeared symmetric. The remainder of the evaluation was normal.
Blood levels of cobalamin and cortisol were normal; additional laboratory test results are shown in Table 1. On a repeat lumbar puncture, the opening pressure was 14 cm of water; other results are shown in Table 1. Tests of the CSF for Lyme disease and for enterovirus, varicella virus, and West Nile virus infection were performed.
Dr. Rapalino: Repeat MRI of the head confirmed the presence of diffuse, symmetric hypointensity on T2-weighted images and showed abnormal susceptibility signal throughout the basal ganglia, thalami, dentate nuclei, and cortical surfaces of the cerebral hemispheres on susceptibility-weighted images (Figure 1).	
Figure 1 
Dr. Balaban: Electroencephalography showed generalized polymorphic theta slowing in the background and frequent, prolonged runs of bifrontal irregular delta activity with embedded bifrontal low-amplitude blunt discharges.
Vancomycin, ceftriaxone, and acyclovir were continued, and meropenem was administered intravenously. During the next 3 days, the patient began to open her eyes spontaneously, move her arms and legs independently, and follow commands intermittently. Increased tone was noted in the legs and arms. Cultures of blood and CSF obtained 72 hours previously showed no growth. The CSF tests for Lyme disease and for enterovirus, varicella virus, and West Nile virus infection were negative. Vancomycin, ceftriaxone, and acyclovir were discontinued, and the patient was transferred from the ICU to the neurology unit.
Additional history was obtained from the patient's neighbors, outpatient endocrinologist, and family. Two years before this presentation, the patient's neighbors had noted the development of suspicious and paranoid beliefs. For example, the patient believed that her computer was being used to spy on her and gather personal information, and she repeatedly asked them to help fix the device.
Approximately 21 months before this presentation, the patient's endocrinologist had noted the development of confusion. The patient began to contact her physician's office repeatedly, often several times daily. Whereas she had previously managed her diabetes with a high degree of sophistication, she began to ask questions that suggested she was having difficulty with basic diabetes management. Her telephone calls contained many unrelated and, at times, nonsensical questions; emails were similarly tangential and incoherent. When she was asked about these changes, the patient reported that her cognitive function was as ""sharp as a tack"" and that her emails were confusing because of ""slow Internet speed."" During an office visit with her endocrinologist, the Mini-Mental State Examination (MMSE) score was 24 on a scale ranging from 0 to 30, with higher scores indicating better cognitive function; points were deducted because the patient had made errors of short-term object recall, attention, and calculation. The patient was referred to the outpatient neurology clinic of the other hospital for further evaluation, but she did not attend the scheduled visit.
Two weeks before the current presentation, the patient's family had noted that she had sent individualized holiday gifts to incorrect family members. In the accompanying holiday cards, her penmanship, which had previously been neat, was nearly illegible and was likened by family members to a child's handwriting.
During the current hospitalization, the patient continued to show slow neurologic improvement with supportive care. She was able to answer questions in short sentences, was oriented to self but not to time or place, and was unable to provide further history about the events that led to her hospitalization. A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Creutzfeldt-Jakob Disease (CJD). The patient's progressive cognitive decline, abnormal MRI findings, and presence of 14-3-3 protein in the cerebrospinal fluid are indicative of CJD. The rapid progression of symptoms and the presence of myoclonus (suggested by the purposeful movement toward changing painful stimuli) are also consistent with this diagnosis.""
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  ""id"": ""chatcmpl-7hus8BPkSo0iIMWzKzDQw1NpM24Hm"",
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        ""role"": ""assistant"",
        ""content"": ""The patient's symptoms include obtundation, unresponsiveness, and abnormal reflexes. The patient's history of type 1 diabetes mellitus and the presence of an insulin pump suggest a possible metabolic cause. However, the blood glucose level was elevated, not low, ruling out hypoglycemia. The presence of protein, glucose, and ketones in the urine suggest diabetic ketoacidosis, but the blood pH was normal, ruling this out. The CT and MRI scans revealed increased attenuation and signal loss in the basal ganglia, thalami, and dentate nuclei, suggesting a neurological cause. The patient's history of suspicious and paranoid beliefs, confusion, and cognitive decline suggest a progressive neurological disorder. The EEG showed generalized slowing without epileptiform activity, which is consistent with encephalopathy. The patient's slow neurological improvement with supportive care further supports a neurological cause. The most likely diagnosis is Creutzfeldt-Jakob disease, a rare and fatal brain disorder that causes rapid, progressive dementia and neurological symptoms.\n\nDiagnosis: Creutzfeldt-Jakob disease.""
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}",Creutzfeldt-Jakob Disease (CJD),N,"{
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        ""content"": ""The patient is a 59-year-old woman with a history of type 1 diabetes mellitus, chronic lymphocytic leukemia, ductal carcinoma in situ of the breast, chronic anemia, asthma, and arthritis due to Lyme disease. She was found unresponsive in her car and has remained obtunded. She has a history of suspicious and paranoid beliefs, confusion, and difficulty with basic diabetes management. Her MMSE score was 24, indicating cognitive impairment. Her blood glucose level was elevated, and urinalysis revealed the presence of protein, glucose, and ketones. CT and MRI of the head revealed increased attenuation in the basal ganglia, thalami, and dentate nuclei. CSF analysis showed rare neutrophils with no organisms and rare atypical cells. \n\nThe differential diagnosis for this patient includes diabetic ketoacidosis, hypoglycemia, stroke, encephalitis, meningitis, and a paraneoplastic syndrome. Diabetic ketoacidosis and hypoglycemia can be ruled out because the patient's blood glucose level was elevated but not to the extent typically seen in diabetic ketoacidosis, and there were no hypoglycemic episodes in the preceding week. Stroke is less likely given the symmetric findings on imaging and the absence of focal neurologic deficits. Encephalitis and meningitis are also less likely given the negative CSF cultures and the absence of organisms on Gram stain. \n\nThe patient's history of cancer, the presence of atypical cells in the CSF, and the cognitive and neurologic symptoms suggest a paraneoplastic syndrome. Paraneoplastic syndromes are rare disorders triggered by an altered immune system response to a neoplasm. They are defined by clinical manifestations of organ or tissue damage away from the tumor site. The patient's history of chronic lymphocytic leukemia and breast cancer, along with her neurologic symptoms and the presence of atypical cells in the CSF, support this diagnosis.\n\nDiagnosis: Paraneoplastic syndrome.""
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}",Paraneoplastic syndrome,N
10.1056/NEJMcpc2002415,Case 34-2020: A 74-Year-Old Man with Chronic Kidney Disease,"White-cell count (per μl) 4700–10,900 5410
Hemoglobin (g/dl)   10.5
Hematocrit (%)  33.8
Platelet count (per μl)   168,000
Erythrocyte sedimentation rate 
(mm/hr)
  61
C-reactive protein (mg/liter)  .0 13.8
Sodium (mmol/liter)   138
Potassium (mmol/liter)   5.3
Chloride (mmol/liter) 98–107 102
Carbon dioxide (mmol/liter) 21–30 19
Anion gap (mmol/liter)   17
Urea nitrogen (mg/dl)   53
Creatinine (mg/dl)   3.41
Glucose (mg/dl) 70–109 156
Calcium (mg/dl) 8.9–10.0 9.2
Protein (g/dl)
Total 6.4–8.3 8.5
Albumin   3.8
Globulin   4.7
Urine
Creatinine (mg/dl) 67
Total protein (mg/dl) 0. .5 149.6
Protein:creatinine ratio <0.15 2.23","IgG4-related disease, with tubulointerstitial nephritis, membranous nephropathy, and inflammatory pseudotumor involving the lacrimal gla",IgG4-related disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 74-year-old man was evaluated in the nephrology clinic of this hospital because of chronic kidney disease.
The patient had been in his usual state of health when he was referred to the nephrology clinic of this hospital for a preoperative evaluation of chronic kidney disease, before a transcatheter aortic-valve replacement (TAVR) for aortic stenosis.
Eighteen years before this evaluation, an elevated creatinine level had been found incidentally during an evaluation of fatigue, malaise, and joint stiffness. The patient was evaluated in the nephrology clinic of another hospital, and biopsy of the right kidney was performed.
Dr. Robert B. Colvin: Pathological examination of the kidney-biopsy specimen (Figure 1) revealed glomeruli with thickened capillary walls and mild mesangial hypercellularity. A Jones' silver stain showed ""spikes"" and ""bubbles"" in the glomerular basement membrane, features typical of membranous nephropathy. The interstitium had an infiltrate of mononuclear cells, plasma cells, and eosinophils, with tubulitis and without granulomas or neutrophils. Immunofluorescence showed staining of granular deposits for IgG and C3 along the glomerular basement membrane and in the mesangium. Other stains (C1q, IgA, IgM, fibrinogen, and albumin) were negative. Electron microscopy showed widespread amorphous subepithelial deposits along the glomerular basement membrane and in the mesangium, with surrounding spikes and podocyte foot-process effacement. Arteriosclerosis and glomerulosclerosis were also present. At the other hospital, these findings were interpreted as membranous nephropathy, acute tubulointerstitial nephritis with eosinophils, and arterionephrosclerosis with global glomerulosclerosis.	
Figure 1 
Dr. Rhee: The patient was told that his kidney disease was consistent with a diagnosis of Sjogren's syndrome. Prednisone was administered for 6 months and then tapered to a lower dose. Treatment with sodium bicarbonate and furosemide was initiated, as was treatment with losartan, although losartan was intermittently stopped because of hyperkalemia; prednisone was continued. During the next 18 years, the creatinine level gradually increased to 3.28 mg per deciliter (290 [mu]mol per liter; reference range, 0.70 to 1.18 mg per deciliter [62 to 104 [mu]mol per liter]).
Twenty-five years before the current evaluation, the patient had received a diagnosis of chronic pancreatitis complicated by diabetes mellitus and exocrine pancreatic insufficiency. One year later, painless enlargement of the right lacrimal gland occurred. Surgical excision of the right lacrimal gland was performed at the other hospital, and examination of the excised specimen reportedly revealed nonspecific inflammation. The next year, enlargement of the left lacrimal gland and the bilateral submandibular and parotid glands developed.
Dr. Sumit Gupta: Magnetic resonance imaging of the neck, performed before and after the administration of intravenous contrast material, revealed masslike abnormalities of the bilateral submandibular and parotid glands. The abnormalities were hypointense on T1-weighted and T2-weighted imaging.
Dr. Rhee: The patient declined another glandular biopsy and was told that he probably had Sjogren's syndrome. Glandular enlargement resolved, and during the next 23 years, the patient was treated with prednisone for presumptive Sjogren's syndrome.
Two years before the current evaluation, shortness of breath and substernal chest pressure on exertion developed; these symptoms usually resolved after approximately 20 minutes of rest. The patient was evaluated at the other hospital, and aortic stenosis was diagnosed.
Four months before the current evaluation, the shortness of breath and substernal chest pressure worsened, such that the patient became unable to carry his groceries a short distance to his house. Additional imaging and cardiology studies were obtained.
Dr. Gupta: Computed tomography (CT) of the heart, chest, abdomen, and pelvis, performed before and after the administration of intravenous contrast material, revealed multiple large aneurysms involving all the coronary arteries, with associated mural thrombus (Figure 2A through 2D; and Video 1, available with the full text of this article at
NEJM.org
). There was extensive coronary-artery calcification, along with scattered pulmonary nodules measuring up to 4 mm in diameter, multiple mildly enlarged mediastinal lymph nodes, and calcification in the tail of the pancreas.	
Figure 2
Dr. Rahul Sakhuja: Echocardiography showed severe tricuspid aortic stenosis, with bulky calcification of the aortic-valve leaflets with restricted motion (Video 2, available at
NEJM.org
), as well as severe calcification of the aortic root at the sinotubular junction. Coronary angiography revealed large aneurysms with partial calcification involving all the coronary arteries - specifically, the distal left main, proximal and middle left anterior descending, proximal left circumflex, and proximal and middle right coronary arteries - and calcified narrowing between the aneurysmal segments (Figure 2E through 2H). The distal lumens were normal in caliber and were not well visualized because of the slow flow through the proximal aneurysmal segments. There was moderate, diffuse disease in the middle left circumflex artery.
Dr. Rhee: Balloon aortic valvuloplasty was performed 3 months before the current evaluation, and a subsequent TAVR was planned. During the current evaluation, the patient indicated that the shortness of breath and chest pressure on exertion had abated since the balloon aortic valvuloplasty. Additional history was obtained. The patient had chronic back and neck pain due to severe kyphoscoliosis, spinal stenosis, and cervical myelopathy; the pain had been treated 2 months earlier with anterior cervical diskectomy and fusion. He had hypertension, anemia, gout, osteopenia, and benign prostatic hypertrophy. Medications included prednisone, metoprolol, aspirin, rosuvastatin, furosemide, insulin, sodium bicarbonate, epoetin alfa, cholecalciferol, calcitriol, pancrelipase, alfuzosin, allopurinol, and gabapentin. There were no known drug allergies. He had smoked 10 cigarettes per day for 6 years but had stopped four decades earlier; he drank alcohol rarely and did not use illicit drugs. The patient had been retired from his career as a health care professional for 2 years. He was married and lived in a house in a suburban area of New England. His father had had type 2 diabetes mellitus and had died of prostate cancer at 67 years of age, his mother had had pancreatic cancer and had died at 65 years of age, and his younger brother had had type 2 diabetes mellitus and had died after a myocardial infarction at 46 years of age.
On physical examination, the temperature was 36.1[degrees]C, the blood pressure 176/75 mm Hg, the heart rate 77 beats per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.8. There was a crescendo-decrescendo systolic murmur that was heard best at the right upper sternal border. The creatinine level was 3.41 mg per deciliter (301 [mu]mol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 [mu]mol per liter]), which was similar to other levels obtained during the previous 1.5 years. The urinary protein level was 149.6 mg per deciliter (reference range, 0.0 to 13.5); the ratio of total protein to creatinine was 2.23 (reference range, <0.15). Results of liver-function tests were normal. Other laboratory test results are shown in Table 1.	
Table 1
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 74-year-old man was evaluated in the nephrology clinic of this hospital because of chronic kidney disease.
The patient had been in his usual state of health when he was referred to the nephrology clinic of this hospital for a preoperative evaluation of chronic kidney disease, before a transcatheter aortic-valve replacement (TAVR) for aortic stenosis.
Eighteen years before this evaluation, an elevated creatinine level had been found incidentally during an evaluation of fatigue, malaise, and joint stiffness. The patient was evaluated in the nephrology clinic of another hospital, and biopsy of the right kidney was performed.
Dr. Robert B. Colvin: Pathological examination of the kidney-biopsy specimen (Figure 1) revealed glomeruli with thickened capillary walls and mild mesangial hypercellularity. A Jones' silver stain showed ""spikes"" and ""bubbles"" in the glomerular basement membrane, features typical of membranous nephropathy. The interstitium had an infiltrate of mononuclear cells, plasma cells, and eosinophils, with tubulitis and without granulomas or neutrophils. Immunofluorescence showed staining of granular deposits for IgG and C3 along the glomerular basement membrane and in the mesangium. Other stains (C1q, IgA, IgM, fibrinogen, and albumin) were negative. Electron microscopy showed widespread amorphous subepithelial deposits along the glomerular basement membrane and in the mesangium, with surrounding spikes and podocyte foot-process effacement. Arteriosclerosis and glomerulosclerosis were also present. At the other hospital, these findings were interpreted as membranous nephropathy, acute tubulointerstitial nephritis with eosinophils, and arterionephrosclerosis with global glomerulosclerosis.	
Figure 1 
Dr. Rhee: The patient was told that his kidney disease was consistent with a diagnosis of Sjogren's syndrome. Prednisone was administered for 6 months and then tapered to a lower dose. Treatment with sodium bicarbonate and furosemide was initiated, as was treatment with losartan, although losartan was intermittently stopped because of hyperkalemia; prednisone was continued. During the next 18 years, the creatinine level gradually increased to 3.28 mg per deciliter (290 [mu]mol per liter; reference range, 0.70 to 1.18 mg per deciliter [62 to 104 [mu]mol per liter]).
Twenty-five years before the current evaluation, the patient had received a diagnosis of chronic pancreatitis complicated by diabetes mellitus and exocrine pancreatic insufficiency. One year later, painless enlargement of the right lacrimal gland occurred. Surgical excision of the right lacrimal gland was performed at the other hospital, and examination of the excised specimen reportedly revealed nonspecific inflammation. The next year, enlargement of the left lacrimal gland and the bilateral submandibular and parotid glands developed.
Dr. Sumit Gupta: Magnetic resonance imaging of the neck, performed before and after the administration of intravenous contrast material, revealed masslike abnormalities of the bilateral submandibular and parotid glands. The abnormalities were hypointense on T1-weighted and T2-weighted imaging.
Dr. Rhee: The patient declined another glandular biopsy and was told that he probably had Sjogren's syndrome. Glandular enlargement resolved, and during the next 23 years, the patient was treated with prednisone for presumptive Sjogren's syndrome.
Two years before the current evaluation, shortness of breath and substernal chest pressure on exertion developed; these symptoms usually resolved after approximately 20 minutes of rest. The patient was evaluated at the other hospital, and aortic stenosis was diagnosed.
Four months before the current evaluation, the shortness of breath and substernal chest pressure worsened, such that the patient became unable to carry his groceries a short distance to his house. Additional imaging and cardiology studies were obtained.
Dr. Gupta: Computed tomography (CT) of the heart, chest, abdomen, and pelvis, performed before and after the administration of intravenous contrast material, revealed multiple large aneurysms involving all the coronary arteries, with associated mural thrombus (Figure 2A through 2D; and Video 1, available with the full text of this article at
NEJM.org
). There was extensive coronary-artery calcification, along with scattered pulmonary nodules measuring up to 4 mm in diameter, multiple mildly enlarged mediastinal lymph nodes, and calcification in the tail of the pancreas.	
Figure 2
Dr. Rahul Sakhuja: Echocardiography showed severe tricuspid aortic stenosis, with bulky calcification of the aortic-valve leaflets with restricted motion (Video 2, available at
NEJM.org
), as well as severe calcification of the aortic root at the sinotubular junction. Coronary angiography revealed large aneurysms with partial calcification involving all the coronary arteries - specifically, the distal left main, proximal and middle left anterior descending, proximal left circumflex, and proximal and middle right coronary arteries - and calcified narrowing between the aneurysmal segments (Figure 2E through 2H). The distal lumens were normal in caliber and were not well visualized because of the slow flow through the proximal aneurysmal segments. There was moderate, diffuse disease in the middle left circumflex artery.
Dr. Rhee: Balloon aortic valvuloplasty was performed 3 months before the current evaluation, and a subsequent TAVR was planned. During the current evaluation, the patient indicated that the shortness of breath and chest pressure on exertion had abated since the balloon aortic valvuloplasty. Additional history was obtained. The patient had chronic back and neck pain due to severe kyphoscoliosis, spinal stenosis, and cervical myelopathy; the pain had been treated 2 months earlier with anterior cervical diskectomy and fusion. He had hypertension, anemia, gout, osteopenia, and benign prostatic hypertrophy. Medications included prednisone, metoprolol, aspirin, rosuvastatin, furosemide, insulin, sodium bicarbonate, epoetin alfa, cholecalciferol, calcitriol, pancrelipase, alfuzosin, allopurinol, and gabapentin. There were no known drug allergies. He had smoked 10 cigarettes per day for 6 years but had stopped four decades earlier; he drank alcohol rarely and did not use illicit drugs. The patient had been retired from his career as a health care professional for 2 years. He was married and lived in a house in a suburban area of New England. His father had had type 2 diabetes mellitus and had died of prostate cancer at 67 years of age, his mother had had pancreatic cancer and had died at 65 years of age, and his younger brother had had type 2 diabetes mellitus and had died after a myocardial infarction at 46 years of age.
On physical examination, the temperature was 36.1[degrees]C, the blood pressure 176/75 mm Hg, the heart rate 77 beats per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.8. There was a crescendo-decrescendo systolic murmur that was heard best at the right upper sternal border. The creatinine level was 3.41 mg per deciliter (301 [mu]mol per liter; reference range, 0.60 to 1.50 mg per deciliter [53 to 133 [mu]mol per liter]), which was similar to other levels obtained during the previous 1.5 years. The urinary protein level was 149.6 mg per deciliter (reference range, 0.0 to 13.5); the ratio of total protein to creatinine was 2.23 (reference range, <0.15). Results of liver-function tests were normal. Other laboratory test results are shown in Table 1.	
Table 1
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""IgG4-related disease. The patient's history of chronic pancreatitis, kidney disease, and glandular involvement, along with the presence of coronary artery aneurysms, are all consistent with this condition. The kidney biopsy showing tubulointerstitial nephritis with eosinophils and the presence of IgG and C3 along the glomerular basement membrane and in the mesangium further support this diagnosis. The patient's response to prednisone treatment is also consistent with IgG4-related disease, as corticosteroids are the first-line treatment for this condition.""
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        ""content"": ""The patient is a 74-year-old man with a history of chronic kidney disease, aortic stenosis, and chronic pancreatitis complicated by diabetes mellitus and exocrine pancreatic insufficiency. He also has a history of glandular enlargement and was previously diagnosed with Sjogren's syndrome. The patient's kidney biopsy revealed membranous nephropathy, acute tubulointerstitial nephritis with eosinophils, and arterionephrosclerosis with global glomerulosclerosis. The patient also has coronary artery aneurysms. The differential diagnosis for this patient includes Sjogren's syndrome, systemic lupus erythematosus (SLE), IgG4-related disease, and polyarteritis nodosa. SLE can be ruled out due to the absence of other systemic symptoms and negative ANA. Polyarteritis nodosa can also be ruled out due to the absence of systemic symptoms and negative ANCA. The patient's history of glandular enlargement, membranous nephropathy, and coronary artery aneurysms is suggestive of IgG4-related disease. Furthermore, the patient's response to prednisone is also consistent with IgG4-related disease. \n\nDiagnosis: IgG4-related disease.""
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10.1056/NEJMcpc1916257,"Case 33-2020: A 55-Year-Old Man with Abdominal Pain, Joint Swelling, and Skin Lesions","Hematocrit (%)   25.3
Hemoglobin (g/dl)   7.6
White-cell count (per μl)   12,450
Differential count (per μl)
Neutrophils   11,329.5
Lymphocytes   435.75
Monocytes   435.75
Eosinophils   0
Basophils  00 0
Platelet count (per μl)   395,000
Red-cell count (per μl) 4,500,000–
5,900,000
2,680,000
Mean corpuscular volume (fl)   94.4
Mean corpuscular hemoglobin (pg) 26–34 28.4
Mean corpuscular hemoglobin con‚Äë
centration (g/dl)
31–37 30
Lipase (U/liter) 13–60 5338
Total protein (g/dl) 6. .3 5.3
Albumin (g/dl)   2.3","Pancreatitis, panniculitis, and polyarthritis syndrome","Pancreatitis, panniculitis, and polyarthritis syndrome","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 55-year-old man was transferred to this hospital from a rehabilitation facility because of abdominal pain and painful skin lesions.
One year before the current presentation, the patient received a diagnosis of pancreatitis at another hospital after magnetic resonance cholangiopancreatography (MRCP) performed for the evaluation of chronic abdominal pain revealed pancreatic necrosis and peripancreatic fat stranding involving the pancreatic head and uncinate process. Blood levels of triglycerides and IgG subclasses were reportedly normal, and the patient had not been drinking alcohol; the pancreatitis was attributed to bevacizumab, which had been administered for the treatment of neurofibromatosis. Bevacizumab therapy was stopped for 2 months. After bevacizumab therapy was restarted, elevated blood lipase levels recurred without any abdominal symptoms, and bevacizumab therapy was discontinued.
Seven months before the current presentation, another MRCP showed pancreatic ductal dilatation and a pancreatic pseudocyst with internal calcification. Endoscopic ultrasonography revealed changes consistent with chronic pancreatitis and a pancreatic pseudocyst. The patient was advised to continue to avoid alcohol and fatty foods. Blood lipase levels returned to normal.
Three and half months before the current presentation, pain in the ankles developed. The patient reported that the pain was worse after prolonged rest and that his ankles felt stiff for 1 hour after he awoke in the morning. Two weeks later, pain, redness, and swelling in the left lower leg developed, with a central fluctuant nodule on an erythematous base (Figure 1A). Over the next 2 weeks, swelling and redness of the left fifth toe and the right first metacarpophalangeal joint developed (Figure 1B and 1C). The patient was evaluated by his primary care physician. Range of motion was limited in the ankles, which had overlying soft-tissue swelling and tenderness on palpation. There was also erythema, tenderness, and soft-tissue swelling of the right fourth metacarpophalangeal joint, the left second and third metacarpophalangeal joints, and the right fourth proximal interphalangeal joint of the hand. The erythrocyte sedimentation rate was 76 mm per hour (reference range, 0 to 15), and the C-reactive protein level was 102 mg per liter (reference range, 0 to 8). Blood levels of calcium, uric acid, angiotensin-converting enzyme, rheumatoid factor, cyclic citrullinated peptide, streptolysin, and DNase were normal; tests for antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative. A chest radiograph was normal. Empirical treatment with cephalexin was administered.	
Figure 1 
After several days, the patient's condition had not improved, and he was evaluated by a rheumatologist. He received a diagnosis of possible Lofgren's syndrome, and prednisone was prescribed. Over the next 2 weeks, there was a decrease in the swelling and pain in the left fifth toe and right first metacarpophalangeal joint but not in the ankle pain or the skin lesion in the left leg. Pain in the ankles worsened, was minimally alleviated with the administration of oxycodone, and limited the patient's ability to walk. The dose of prednisone was increased, and colchicine was administered, with a decrease in the ankle pain and resolution of the skin lesion in the left leg.
Five weeks before the current presentation, the patient was admitted to a second hospital with septic and hemorrhagic shock in the context of infected pancreatic necrosis and bleeding from a gastroduodenal artery pseudoaneurysm.
Dr. Lauren A. Roller: Computed tomographic (CT) angiography of the abdomen and pelvis revealed multiple peripancreatic fluid collections and irregularity of the branch vessels of the celiac and superior mesenteric arteries, including the gastroduodenal artery, adjacent to areas of pancreatic necrosis and inflammation (Figure 2A and 2B).	
Figure 2 
Dr. D'Silva: Percutaneous drainage of the pancreatic necrosis and angioembolization of the gastroduodenal artery pseudoaneurysm were performed. On the fourth hospital day, the patient was transferred to this hospital for further treatment.
At this hospital, five intraabdominal drainage catheters were placed, with a decrease in the size of the multifocal fluid collections in the abdomen. Cultures of intraabdominal fluid grew Pantoea agglomerans (formerly Enterobacter agglomerans), abiotrophia species (formerly nutritionally variant streptococci), and lactobacillus species. The patient completed a course of piperacillin in combination with tazobactam and was discharged from this hospital to a rehabilitation facility on the 24th hospital day.
Seven days after discharge, periumbilical and right lower abdominal pain developed, and the patient returned to the emergency department of this hospital for evaluation. There was no fever, nausea, vomiting, or joint pain. He reported 5 days of painful skin lesions and swelling of the right leg.
Other medical history included hypertension, neurofibromatosis type 2, gastroesophageal reflux disease, sensorineural hearing loss, benign prostatic hypertrophy, and anxiety. There was no history of sinusitis, inflammatory eye disease, neuropathy, or testicular disease. Neurofibromatosis had been complicated by cervical spine ependymoma, meningiomas, and vestibular schwannomas and had been treated with bevacizumab for 8 months before the diagnosis of pancreatitis. Medications included aspirin, gabapentin, hydrochlorothiazide, lorazepam, losartan, metoprolol, omeprazole, oxycodone, pancrelipase, prednisone, tamsulosin, and tolterodine. There was a history of heavy alcohol use, but the patient had stopped drinking alcohol 3 years before this presentation. There was a remote history of tobacco use and no history of illicit drug use. He lived with his mother in a suburb of Boston.
The temperature was 37.3[degrees]C, the blood pressure 107/68 mm Hg, the pulse 118 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 73.6 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 22. The abdomen was soft and nontender, with five percutaneous drainage catheters in place. There was pitting edema in the right foot. A blanching, erythematous, indurated plaque (5 cm in diameter) with superficial scale was present on the medial aspect of the right knee (Figure 1D); a similar lesion (1 cm in diameter) was present on the superior aspect of the right knee. There were two blanching, erythematous, thin plaques (1 cm in diameter) on the left lateral calf (Figure 1E). There were several nontender, hyperpigmented patches on the lower legs that were consistent with postinflammatory hyperpigmentation. There was pain on palpation and diffuse erythema and warmth of the right lower calf. The remainder of the physical examination was normal.
Blood levels of electrolytes and glucose were normal, as were results of kidney- and liver-function tests. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Roller: CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a slight decrease in the size of multiple necrotic peripancreatic fluid collections, with drainage catheters in place (Figure 2C). There was evidence of previous embolization of the gastroduodenal artery without evidence of residual or new pseudoaneurysm. Duplex ultrasonography of the right leg showed nonocclusive thrombosis in the distal right femoral vein.
Dr. D'Silva: A specimen of fluid from the largest abdominal collection and a specimen of blood were obtained for culture; ceftriaxone was administered. A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 55-year-old man was transferred to this hospital from a rehabilitation facility because of abdominal pain and painful skin lesions.
One year before the current presentation, the patient received a diagnosis of pancreatitis at another hospital after magnetic resonance cholangiopancreatography (MRCP) performed for the evaluation of chronic abdominal pain revealed pancreatic necrosis and peripancreatic fat stranding involving the pancreatic head and uncinate process. Blood levels of triglycerides and IgG subclasses were reportedly normal, and the patient had not been drinking alcohol; the pancreatitis was attributed to bevacizumab, which had been administered for the treatment of neurofibromatosis. Bevacizumab therapy was stopped for 2 months. After bevacizumab therapy was restarted, elevated blood lipase levels recurred without any abdominal symptoms, and bevacizumab therapy was discontinued.
Seven months before the current presentation, another MRCP showed pancreatic ductal dilatation and a pancreatic pseudocyst with internal calcification. Endoscopic ultrasonography revealed changes consistent with chronic pancreatitis and a pancreatic pseudocyst. The patient was advised to continue to avoid alcohol and fatty foods. Blood lipase levels returned to normal.
Three and half months before the current presentation, pain in the ankles developed. The patient reported that the pain was worse after prolonged rest and that his ankles felt stiff for 1 hour after he awoke in the morning. Two weeks later, pain, redness, and swelling in the left lower leg developed, with a central fluctuant nodule on an erythematous base (Figure 1A). Over the next 2 weeks, swelling and redness of the left fifth toe and the right first metacarpophalangeal joint developed (Figure 1B and 1C). The patient was evaluated by his primary care physician. Range of motion was limited in the ankles, which had overlying soft-tissue swelling and tenderness on palpation. There was also erythema, tenderness, and soft-tissue swelling of the right fourth metacarpophalangeal joint, the left second and third metacarpophalangeal joints, and the right fourth proximal interphalangeal joint of the hand. The erythrocyte sedimentation rate was 76 mm per hour (reference range, 0 to 15), and the C-reactive protein level was 102 mg per liter (reference range, 0 to 8). Blood levels of calcium, uric acid, angiotensin-converting enzyme, rheumatoid factor, cyclic citrullinated peptide, streptolysin, and DNase were normal; tests for antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative. A chest radiograph was normal. Empirical treatment with cephalexin was administered.	
Figure 1 
After several days, the patient's condition had not improved, and he was evaluated by a rheumatologist. He received a diagnosis of possible Lofgren's syndrome, and prednisone was prescribed. Over the next 2 weeks, there was a decrease in the swelling and pain in the left fifth toe and right first metacarpophalangeal joint but not in the ankle pain or the skin lesion in the left leg. Pain in the ankles worsened, was minimally alleviated with the administration of oxycodone, and limited the patient's ability to walk. The dose of prednisone was increased, and colchicine was administered, with a decrease in the ankle pain and resolution of the skin lesion in the left leg.
Five weeks before the current presentation, the patient was admitted to a second hospital with septic and hemorrhagic shock in the context of infected pancreatic necrosis and bleeding from a gastroduodenal artery pseudoaneurysm.
Dr. Lauren A. Roller: Computed tomographic (CT) angiography of the abdomen and pelvis revealed multiple peripancreatic fluid collections and irregularity of the branch vessels of the celiac and superior mesenteric arteries, including the gastroduodenal artery, adjacent to areas of pancreatic necrosis and inflammation (Figure 2A and 2B).	
Figure 2 
Dr. D'Silva: Percutaneous drainage of the pancreatic necrosis and angioembolization of the gastroduodenal artery pseudoaneurysm were performed. On the fourth hospital day, the patient was transferred to this hospital for further treatment.
At this hospital, five intraabdominal drainage catheters were placed, with a decrease in the size of the multifocal fluid collections in the abdomen. Cultures of intraabdominal fluid grew Pantoea agglomerans (formerly Enterobacter agglomerans), abiotrophia species (formerly nutritionally variant streptococci), and lactobacillus species. The patient completed a course of piperacillin in combination with tazobactam and was discharged from this hospital to a rehabilitation facility on the 24th hospital day.
Seven days after discharge, periumbilical and right lower abdominal pain developed, and the patient returned to the emergency department of this hospital for evaluation. There was no fever, nausea, vomiting, or joint pain. He reported 5 days of painful skin lesions and swelling of the right leg.
Other medical history included hypertension, neurofibromatosis type 2, gastroesophageal reflux disease, sensorineural hearing loss, benign prostatic hypertrophy, and anxiety. There was no history of sinusitis, inflammatory eye disease, neuropathy, or testicular disease. Neurofibromatosis had been complicated by cervical spine ependymoma, meningiomas, and vestibular schwannomas and had been treated with bevacizumab for 8 months before the diagnosis of pancreatitis. Medications included aspirin, gabapentin, hydrochlorothiazide, lorazepam, losartan, metoprolol, omeprazole, oxycodone, pancrelipase, prednisone, tamsulosin, and tolterodine. There was a history of heavy alcohol use, but the patient had stopped drinking alcohol 3 years before this presentation. There was a remote history of tobacco use and no history of illicit drug use. He lived with his mother in a suburb of Boston.
The temperature was 37.3[degrees]C, the blood pressure 107/68 mm Hg, the pulse 118 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 73.6 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 22. The abdomen was soft and nontender, with five percutaneous drainage catheters in place. There was pitting edema in the right foot. A blanching, erythematous, indurated plaque (5 cm in diameter) with superficial scale was present on the medial aspect of the right knee (Figure 1D); a similar lesion (1 cm in diameter) was present on the superior aspect of the right knee. There were two blanching, erythematous, thin plaques (1 cm in diameter) on the left lateral calf (Figure 1E). There were several nontender, hyperpigmented patches on the lower legs that were consistent with postinflammatory hyperpigmentation. There was pain on palpation and diffuse erythema and warmth of the right lower calf. The remainder of the physical examination was normal.
Blood levels of electrolytes and glucose were normal, as were results of kidney- and liver-function tests. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Roller: CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a slight decrease in the size of multiple necrotic peripancreatic fluid collections, with drainage catheters in place (Figure 2C). There was evidence of previous embolization of the gastroduodenal artery without evidence of residual or new pseudoaneurysm. Duplex ultrasonography of the right leg showed nonocclusive thrombosis in the distal right femoral vein.
Dr. D'Silva: A specimen of fluid from the largest abdominal collection and a specimen of blood were obtained for culture; ceftriaxone was administered. A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Pancreatic panniculitis is the most likely diagnosis. This patient has a history of pancreatitis and presents with painful skin lesions and swelling of the right leg. Pancreatic panniculitis is a rare skin manifestation of pancreatic disease, often pancreatitis or pancreatic carcinoma, and presents as erythematous, tender nodules on the lower extremities. The patient's skin lesions, history of pancreatitis, and the presence of pancreatic pseudocyst with internal calcification on MRCP support this diagnosis.""
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        ""content"": ""Neurofibromatosis type 2 with pancreatitis and infected pancreatic necrosis. The patient's history of neurofibromatosis type 2, pancreatitis, and infected pancreatic necrosis, along with the presence of abdominal pain and skin lesions, lead to this diagnosis. The patient's pancreatitis was previously attributed to bevacizumab, a medication used to treat his neurofibromatosis. The patient also had a history of pancreatic pseudocyst and chronic pancreatitis. The patient's current symptoms of abdominal pain and skin lesions, along with the history of infected pancreatic necrosis, suggest a recurrence or continuation of these conditions.""
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}",Neurofibromatosis type 2 with pancreatitis and infected pancreatic necrosis,N,"{
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        ""content"": ""The patient is a 55-year-old man with a history of pancreatitis and neurofibromatosis type 2, presenting with abdominal pain and painful skin lesions. His history of pancreatitis is complicated by pancreatic necrosis and a pancreatic pseudocyst. He also has a history of joint pain and swelling, which was previously diagnosed as possible Lofgren's syndrome. His current presentation includes abdominal pain, painful skin lesions, and swelling of the right leg. The differential diagnosis for this patient includes infection, autoimmune disease, and malignancy. Given his history of pancreatitis and the recent growth of Pantoea agglomerans, abiotrophia species, and lactobacillus species from intraabdominal fluid, an infectious process is likely. However, his skin lesions and joint pain could also suggest an autoimmune process. His history of neurofibromatosis type 2 also raises the possibility of malignancy. However, the patient's skin lesions are described as blanching, erythematous, indurated plaques with superficial scale, which is not characteristic of malignancy. His joint pain and swelling could be due to an autoimmune process, but his negative antinuclear antibodies and antineutrophil cytoplasmic antibodies make this less likely. Given his history of pancreatitis and recent infection, it is most likely that his current symptoms are due to an ongoing infectious process. \n\nDiagnosis: Infection secondary to pancreatic necrosis.""
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10.1056/NEJMcpc2004996,"Case 32-2020: A 63-Year-Old Man with Confusion, Fatigue, and Garbled Speech","Hemoglobin (g/dl)   10.8 10.4
Hematocrit (%) 46.0–56.0 31.6 30.2
Red-cell count (per μl)   3,580,000 3,460,000
White-cell count (per μl)   7300 13,970
Differential count (per μl)
Neutrophils   5767 11,651
Lymphocytes   876 1173
Monocytes   511 1048
Eosinophils   0 14
Basophils  00 0 14
Platelet count (per μl)   269,000 462,000
Sodium (mmol/liter)   132 133
Potassium (mmol/liter)   4.2 4.2
Chloride (mmol/liter)   95 90
Carbon dioxide (mmol/liter)   31 29
Urea nitrogen (mg/dl)   19 19
Creatinine (mg/dl)   0.76 0.87
Glucose (mg/dl)   134 105
C-reactive protein (mg/liter)   39.7 6.7
Erythrocyte sedimentation rate (mm/hr)   12 8",Borrelia miyamotoi infection.,Borrelia miyamotoi infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 63-year-old man was evaluated at this hospital in the spring because of fever, confusion, headache, garbled speech, fatigue, vision changes, lymphocytic pleocytosis, and an elevated protein level in the cerebrospinal fluid (CSF).
Approximately 5 years before the current presentation, the patient had received a diagnosis of primary membranous nephropathy at another hospital. Treatment with oral prednisone and cyclosporine was initiated.
Two years later, the patient was referred to the nephrology clinic of this hospital for worsening proteinuria and hypertension; rituximab, prednisone, and cyclophosphamide were administered. During the next 21 months, he received four doses of rituximab, the last of which was administered 3 months before this presentation.
Three months before this presentation, the patient had a flash of light accompanied by transient sharp pain in the left retro-orbital area and forehead, with monocular blurry vision. He was subsequently evaluated at the other hospital. Magnetic resonance imaging (MRI) and computed tomography (CT) of the head were normal. Intravenous normal saline was administered, and he was discharged. One week later, the patient was reevaluated at the same hospital for an episode of garbled and nonsensical speech with impaired comprehension that resolved after 10 minutes. A CT angiogram and an MRI of the head reportedly showed a subacute infarct in the right side of the pons; intravenous alteplase was administered. Transthoracic echocardiography (TTE) was normal. Mild word-finding difficulties and confusion persisted.
After discharge, the patient had worsening vision with floaters in the left eye, headache, photophobia, sonophobia, and fatigue. Three weeks later, he was evaluated by a neuro-ophthalmologist, who prescribed oral butalbital-acetaminophen-caffeine therapy and ophthalmic prednisolone drops for suspected uveitis. The vision improved, and headaches decreased during the subsequent 2 weeks; however, 1 week later, he was readmitted to the other hospital with sudden onset of weakness on the right side, facial droop, and garbled speech. The weakness resolved after 10 minutes. CT and MRI of the head and TTE were reportedly unchanged from the previous imaging studies. An electroencephalogram (EEG) showed focal left temporal slowing, and treatment with levetiracetam was initiated. The garbled speech resolved after 2 days, and he was discharged from the hospital.
During the next week, the patient had recurrent staring spells that lasted for 1 minute, during which his family thought he appeared ""vacant""; low-grade fever also developed, and within 48 hours, the temperature increased to 39.4[degrees]C and the garbled speech recurred. He was readmitted to the other hospital, and CT of the head was again reportedly normal. Blood levels of calcium, albumin, globulin, ammonia, thyrotropin, lactate, and troponin T were normal, as were the results of liver-function tests and urinalysis. Tests for Lyme disease antibodies, hepatitis B virus surface antigen, hepatitis C virus antibodies, rapid plasma reagin, antinuclear antibodies, rheumatoid factor, and antineutrophil cytoplasmic antibodies (ANCA) were negative, and levels of complement were normal. Other laboratory test results are shown in Table 1. A lumbar puncture was performed; tests for antibodies to Borrelia burgdorferi and West Nile virus were negative, and a Venereal Disease Research Laboratory (VDRL) test of the CSF was nonreactive (Table 2). The patient was transferred to this hospital for further evaluation.	
Table 1 Table 1Opens a popup window	Table 2 Table 2Opens a popup window	Opens a popup window
A review of systems provided by the patient's family was notable for somnolence, fatigue, generalized weakness, unsteadiness, headaches, staring spells, floaters in the left eye, photophobia, sonophobia, mild neck stiffness, unintentional weight loss of 10 kg in the past 6 months, and nocturia. The patient reported no muscle or joint pain, rash, eye pain, diplopia, oral lesions, cough, dyspnea, nausea, or abdominal pain. His medical history was notable for hypertension, dyslipidemia, early-onset coronary artery disease for which he had received percutaneous coronary intervention in his 50s and for which he had undergone aortocoronary bypass grafting in his 60s, congenital color blindness, colonic polyps, and prostatic hypertrophy. Medications included cyclophosphamide, levetiracetam, aspirin, pravastatin, metoprolol, losartan, hydrochlorothiazide, trimethoprim-sulfamethoxazole, omeprazole, calcium carbonate, cholecalciferol, ferrous sulfate, a multivitamin, and fluticasone. He had not taken other antibiotic agents or nonsteroidal antiinflammatory drugs.
The patient was a retired government employee and lived with his wife in northern New England. He had recently traveled to Florida and to rural Canada and had spent time hunting. He had smoked one pack of cigarettes per day for approximately 30 years but had quit 7 years before the current presentation. He drank two beers per week and did not use illicit substances. His family history included coronary artery disease in both parents and valvular disease in his mother, psoriatic arthritis in a sister, and sarcoidosis in several siblings; there was no history of renal or neurologic disease.
The temperature was 37.2[degrees]C, the heart rate 73 beats per minute, the blood pressure 128/78 mm Hg, and the oxygen saturation 96% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 20.4. He appeared cachectic, with bitemporal wasting. He was somnolent and difficult to arouse with voice; he was oriented to self and intermittently to place, month, and year. His thoughts were perseverative. On mental-status examination, he was unable to name days of the week backward (he named a month and then named the days forward) and was unable to perform serial sevens calculations. Occasional word-finding difficulties were noted, although repetition, naming, and reading were generally intact. When asked to remember three words, he could recall only one word after 5 minutes. He reported that nine quarters equaled $4.25. His affect and speech were intact. The cranial-nerve examination revealed blurriness in the visual fields, ""discomfort"" with eye movements, and limited upward gaze. There was no weakness or pronator drift; a low-amplitude intention tremor was present in the left hand. The muscle tone was increased in both legs, with diffuse hyperreflexia, pectoralis reflexes, and seven beats of ankle clonus. The remainder of the examination was normal.
Blood levels of calcium, magnesium, phosphorus, glycated hemoglobin, bilirubin, albumin, prealbumin, total protein, lactate dehydrogenase, high-density and low-density lipoprotein cholesterol, and thyrotropin were normal, as were the prothrombin time, partial-thromboplastin time, and results of liver-function tests; other laboratory test results are shown in Table 1. A comprehensive urine toxicology screen was negative, and a serum toxicology screen was negative for acetaminophen, salicylates, ethanol, and tricyclic antidepressants. Screening tests for human immunodeficiency virus (HIV) types 1 and 2 and Treponema pallidum were negative. Cultures of the blood and urine were obtained.
Dr. Pamela W. Schaefer: A chest radiograph was normal. CT of the head, performed without the administration of intravenous contrast material, revealed no hemorrhage, acute infarction, or mass lesion. Opacification of the right maxillary sinus was noted. MRI of the head (Fig. 1) and magnetic resonance angiography of the head and neck revealed signal hyperintensity in the sulci on fluid-attenuated inversion recovery images, with associated subtle enhancement on gadolinium-enhanced T1-weighted images; additional subarachnoid and subdural foci characterized by restricted diffusion with no enhancement; nonspecific changes in the white matter; opacification of the right maxillary sinus; and no vascular abnormality. MRI of the spine revealed multilevel degenerative changes, without mass effect on the spinal cord, cord signal abnormality, or abnormal enhancement.	
Figure 1 Figure 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Ard: Intravenous acyclovir, ceftriaxone, ampicillin, vancomycin, and thiamine were administered. On the second hospital day, the temperature was 37.6[degrees]C, and myoclonic jerks were noted; marked lethargy, photophobia, and nonsensical speech persisted. The patient was intermittently impulsive and uncooperative. The white-cell count was 17,960 per microliter (reference range, 4500 to 11,000), and the blood levels of vitamin B12, angiotensin-converting enzyme, complement, and haptoglobin and CD4+ T-cell subset counts were normal. ANCA, antinuclear antibodies, cryptococcal antigen, cytomegalovirus (CMV) DNA, Epstein-Barr virus DNA, galactomannan, and B. burgdorferi antibodies were not detected in the blood. A lumbar puncture was performed; the opening pressure was 10 cm of water, and the CSF was yellow and slightly turbid. Additional results of CSF analysis are shown in Table 2. CSF was obtained for culture, cytologic examination, and an autoimmune encephalopathy panel. An EEG showed intermittent periods of theta slowing in the bilateral posterior quadrants, with no epileptiform discharges.
On examination by an ophthalmologist, bilateral visual acuity, visual fields, and intraocular pressure were normal, and there was no afferent pupillary defect. Slit-lamp examination of the eyes revealed bilateral posterior vitreal detachment but no cells in the anterior or posterior chambers. Dilated-eye examination revealed edema in both optic nerves, with tortuous vessels. There was no evidence of anterior uveitis, retinitis, or retinal necrosis.
On the third hospital day, the temperature was 36.7[degrees]C, and the white-cell count was 8300 per microliter. The patient reported improved strength. Tests for bartonella antibodies and Tropheryma whipplei DNA were negative. Serum protein electrophoresis revealed a diffuse decrease in gamma globulin, with an IgG level of 378 mg per deciliter (reference range, 614 to 1295), an IgA level of 30 mg per deciliter (reference range, 69 to 309), and an IgM level of 7 mg per deciliter (reference range, 53 to 334); the serum free light chain levels and the results of immunoelectrophoresis were normal. A CSF VDRL test was nonreactive, and CSF testing was negative for cryptococcal antigen, eastern equine encephalitis antibodies, enterovirus RNA, West Nile virus RNA, herpes simplex virus (HSV) types 1 and 2 DNA, and varicella-zoster virus (VZV) DNA.
On the fourth hospital day, the patient reported feeling better and having increased strength, which allowed him to walk. Blood tests for cryoglobulin, 1,3-[beta]-d-glucan, and thyroid peroxidase antibodies were negative.
On the fifth hospital day, the patient was calm and cooperative; oriented to person, place, and time; and able to follow complex commands. CSF tests for listeria antibodies, Epstein-Barr virus DNA, and human herpesvirus 6 DNA were negative, as were blood and urine tests for histoplasma antigens. A whole-body positron-emission tomographic (PET)-CT scan did not show fluorodeoxyglucose avidity. The results of a repeat lumbar puncture are shown in Table 2. A repeat ophthalmologic examination revealed the presence of vitreous cells, which were more numerous in the left eye than in the right eye; persistent edema in the left optic nerve; and an increase in the blind spot of the left eye on Humphrey visual-field testing. A fluorescein angiogram showed no evidence of ocular vasculitis.
A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 63-year-old man was evaluated at this hospital in the spring because of fever, confusion, headache, garbled speech, fatigue, vision changes, lymphocytic pleocytosis, and an elevated protein level in the cerebrospinal fluid (CSF).
Approximately 5 years before the current presentation, the patient had received a diagnosis of primary membranous nephropathy at another hospital. Treatment with oral prednisone and cyclosporine was initiated.
Two years later, the patient was referred to the nephrology clinic of this hospital for worsening proteinuria and hypertension; rituximab, prednisone, and cyclophosphamide were administered. During the next 21 months, he received four doses of rituximab, the last of which was administered 3 months before this presentation.
Three months before this presentation, the patient had a flash of light accompanied by transient sharp pain in the left retro-orbital area and forehead, with monocular blurry vision. He was subsequently evaluated at the other hospital. Magnetic resonance imaging (MRI) and computed tomography (CT) of the head were normal. Intravenous normal saline was administered, and he was discharged. One week later, the patient was reevaluated at the same hospital for an episode of garbled and nonsensical speech with impaired comprehension that resolved after 10 minutes. A CT angiogram and an MRI of the head reportedly showed a subacute infarct in the right side of the pons; intravenous alteplase was administered. Transthoracic echocardiography (TTE) was normal. Mild word-finding difficulties and confusion persisted.
After discharge, the patient had worsening vision with floaters in the left eye, headache, photophobia, sonophobia, and fatigue. Three weeks later, he was evaluated by a neuro-ophthalmologist, who prescribed oral butalbital-acetaminophen-caffeine therapy and ophthalmic prednisolone drops for suspected uveitis. The vision improved, and headaches decreased during the subsequent 2 weeks; however, 1 week later, he was readmitted to the other hospital with sudden onset of weakness on the right side, facial droop, and garbled speech. The weakness resolved after 10 minutes. CT and MRI of the head and TTE were reportedly unchanged from the previous imaging studies. An electroencephalogram (EEG) showed focal left temporal slowing, and treatment with levetiracetam was initiated. The garbled speech resolved after 2 days, and he was discharged from the hospital.
During the next week, the patient had recurrent staring spells that lasted for 1 minute, during which his family thought he appeared ""vacant""; low-grade fever also developed, and within 48 hours, the temperature increased to 39.4[degrees]C and the garbled speech recurred. He was readmitted to the other hospital, and CT of the head was again reportedly normal. Blood levels of calcium, albumin, globulin, ammonia, thyrotropin, lactate, and troponin T were normal, as were the results of liver-function tests and urinalysis. Tests for Lyme disease antibodies, hepatitis B virus surface antigen, hepatitis C virus antibodies, rapid plasma reagin, antinuclear antibodies, rheumatoid factor, and antineutrophil cytoplasmic antibodies (ANCA) were negative, and levels of complement were normal. Other laboratory test results are shown in Table 1. A lumbar puncture was performed; tests for antibodies to Borrelia burgdorferi and West Nile virus were negative, and a Venereal Disease Research Laboratory (VDRL) test of the CSF was nonreactive (Table 2). The patient was transferred to this hospital for further evaluation.	
Table 1 Table 1Opens a popup window	Table 2 Table 2Opens a popup window	Opens a popup window
A review of systems provided by the patient's family was notable for somnolence, fatigue, generalized weakness, unsteadiness, headaches, staring spells, floaters in the left eye, photophobia, sonophobia, mild neck stiffness, unintentional weight loss of 10 kg in the past 6 months, and nocturia. The patient reported no muscle or joint pain, rash, eye pain, diplopia, oral lesions, cough, dyspnea, nausea, or abdominal pain. His medical history was notable for hypertension, dyslipidemia, early-onset coronary artery disease for which he had received percutaneous coronary intervention in his 50s and for which he had undergone aortocoronary bypass grafting in his 60s, congenital color blindness, colonic polyps, and prostatic hypertrophy. Medications included cyclophosphamide, levetiracetam, aspirin, pravastatin, metoprolol, losartan, hydrochlorothiazide, trimethoprim-sulfamethoxazole, omeprazole, calcium carbonate, cholecalciferol, ferrous sulfate, a multivitamin, and fluticasone. He had not taken other antibiotic agents or nonsteroidal antiinflammatory drugs.
The patient was a retired government employee and lived with his wife in northern New England. He had recently traveled to Florida and to rural Canada and had spent time hunting. He had smoked one pack of cigarettes per day for approximately 30 years but had quit 7 years before the current presentation. He drank two beers per week and did not use illicit substances. His family history included coronary artery disease in both parents and valvular disease in his mother, psoriatic arthritis in a sister, and sarcoidosis in several siblings; there was no history of renal or neurologic disease.
The temperature was 37.2[degrees]C, the heart rate 73 beats per minute, the blood pressure 128/78 mm Hg, and the oxygen saturation 96% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 20.4. He appeared cachectic, with bitemporal wasting. He was somnolent and difficult to arouse with voice; he was oriented to self and intermittently to place, month, and year. His thoughts were perseverative. On mental-status examination, he was unable to name days of the week backward (he named a month and then named the days forward) and was unable to perform serial sevens calculations. Occasional word-finding difficulties were noted, although repetition, naming, and reading were generally intact. When asked to remember three words, he could recall only one word after 5 minutes. He reported that nine quarters equaled $4.25. His affect and speech were intact. The cranial-nerve examination revealed blurriness in the visual fields, ""discomfort"" with eye movements, and limited upward gaze. There was no weakness or pronator drift; a low-amplitude intention tremor was present in the left hand. The muscle tone was increased in both legs, with diffuse hyperreflexia, pectoralis reflexes, and seven beats of ankle clonus. The remainder of the examination was normal.
Blood levels of calcium, magnesium, phosphorus, glycated hemoglobin, bilirubin, albumin, prealbumin, total protein, lactate dehydrogenase, high-density and low-density lipoprotein cholesterol, and thyrotropin were normal, as were the prothrombin time, partial-thromboplastin time, and results of liver-function tests; other laboratory test results are shown in Table 1. A comprehensive urine toxicology screen was negative, and a serum toxicology screen was negative for acetaminophen, salicylates, ethanol, and tricyclic antidepressants. Screening tests for human immunodeficiency virus (HIV) types 1 and 2 and Treponema pallidum were negative. Cultures of the blood and urine were obtained.
Dr. Pamela W. Schaefer: A chest radiograph was normal. CT of the head, performed without the administration of intravenous contrast material, revealed no hemorrhage, acute infarction, or mass lesion. Opacification of the right maxillary sinus was noted. MRI of the head (Fig. 1) and magnetic resonance angiography of the head and neck revealed signal hyperintensity in the sulci on fluid-attenuated inversion recovery images, with associated subtle enhancement on gadolinium-enhanced T1-weighted images; additional subarachnoid and subdural foci characterized by restricted diffusion with no enhancement; nonspecific changes in the white matter; opacification of the right maxillary sinus; and no vascular abnormality. MRI of the spine revealed multilevel degenerative changes, without mass effect on the spinal cord, cord signal abnormality, or abnormal enhancement.	
Figure 1 Figure 1Opens a popup window	Opens a popup window	Opens a popup window
Dr. Ard: Intravenous acyclovir, ceftriaxone, ampicillin, vancomycin, and thiamine were administered. On the second hospital day, the temperature was 37.6[degrees]C, and myoclonic jerks were noted; marked lethargy, photophobia, and nonsensical speech persisted. The patient was intermittently impulsive and uncooperative. The white-cell count was 17,960 per microliter (reference range, 4500 to 11,000), and the blood levels of vitamin B12, angiotensin-converting enzyme, complement, and haptoglobin and CD4+ T-cell subset counts were normal. ANCA, antinuclear antibodies, cryptococcal antigen, cytomegalovirus (CMV) DNA, Epstein-Barr virus DNA, galactomannan, and B. burgdorferi antibodies were not detected in the blood. A lumbar puncture was performed; the opening pressure was 10 cm of water, and the CSF was yellow and slightly turbid. Additional results of CSF analysis are shown in Table 2. CSF was obtained for culture, cytologic examination, and an autoimmune encephalopathy panel. An EEG showed intermittent periods of theta slowing in the bilateral posterior quadrants, with no epileptiform discharges.
On examination by an ophthalmologist, bilateral visual acuity, visual fields, and intraocular pressure were normal, and there was no afferent pupillary defect. Slit-lamp examination of the eyes revealed bilateral posterior vitreal detachment but no cells in the anterior or posterior chambers. Dilated-eye examination revealed edema in both optic nerves, with tortuous vessels. There was no evidence of anterior uveitis, retinitis, or retinal necrosis.
On the third hospital day, the temperature was 36.7[degrees]C, and the white-cell count was 8300 per microliter. The patient reported improved strength. Tests for bartonella antibodies and Tropheryma whipplei DNA were negative. Serum protein electrophoresis revealed a diffuse decrease in gamma globulin, with an IgG level of 378 mg per deciliter (reference range, 614 to 1295), an IgA level of 30 mg per deciliter (reference range, 69 to 309), and an IgM level of 7 mg per deciliter (reference range, 53 to 334); the serum free light chain levels and the results of immunoelectrophoresis were normal. A CSF VDRL test was nonreactive, and CSF testing was negative for cryptococcal antigen, eastern equine encephalitis antibodies, enterovirus RNA, West Nile virus RNA, herpes simplex virus (HSV) types 1 and 2 DNA, and varicella-zoster virus (VZV) DNA.
On the fourth hospital day, the patient reported feeling better and having increased strength, which allowed him to walk. Blood tests for cryoglobulin, 1,3-[beta]-d-glucan, and thyroid peroxidase antibodies were negative.
On the fifth hospital day, the patient was calm and cooperative; oriented to person, place, and time; and able to follow complex commands. CSF tests for listeria antibodies, Epstein-Barr virus DNA, and human herpesvirus 6 DNA were negative, as were blood and urine tests for histoplasma antigens. A whole-body positron-emission tomographic (PET)-CT scan did not show fluorodeoxyglucose avidity. The results of a repeat lumbar puncture are shown in Table 2. A repeat ophthalmologic examination revealed the presence of vitreous cells, which were more numerous in the left eye than in the right eye; persistent edema in the left optic nerve; and an increase in the blind spot of the left eye on Humphrey visual-field testing. A fluorescein angiogram showed no evidence of ocular vasculitis.
A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fever, confusion, headache, garbled speech, fatigue, vision changes, lymphocytic pleocytosis, and an elevated protein level in the cerebrospinal fluid (CSF) suggest a central nervous system infection. The patient's history of immunosuppressive therapy for membranous nephropathy increases his risk for opportunistic infections. The patient's symptoms did not improve with broad-spectrum antibiotics, suggesting that the cause of his symptoms is not a common bacterial infection. The patient's CSF analysis showed lymphocytic pleocytosis and elevated protein, which are consistent with a viral, fungal, or mycobacterial infection, or an autoimmune or paraneoplastic process. However, extensive infectious workup, including tests for common viral, bacterial, and fungal pathogens, was negative. The patient's symptoms improved without specific antimicrobial therapy, which is not consistent with an untreated infection. The patient's neurologic symptoms, lymphocytic pleocytosis in the CSF, and response to high-dose glucocorticoids are consistent with autoimmune encephalitis. The patient's history of membranous nephropathy, which is often associated with malignancy, raises the possibility of a paraneoplastic syndrome. However, the patient had no evidence of malignancy on PET-CT, making a paraneoplastic process less likely. Therefore, the most likely diagnosis is autoimmune encephalitis.\n\nDiagnosis: Autoimmune Encephalitis.""
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        ""content"": ""The patient's symptoms of fever, confusion, headache, garbled speech, fatigue, vision changes, lymphocytic pleocytosis, and an elevated protein level in the cerebrospinal fluid (CSF) suggest a central nervous system infection. The patient's history of immunosuppressive therapy for membranous nephropathy makes him susceptible to opportunistic infections. The patient's symptoms and CSF findings are not specific to a particular pathogen, but the negative results for common bacterial, viral, and fungal pathogens suggest an atypical or opportunistic infection. The patient's history of hunting and recent travel to rural Canada suggest possible exposure to tick-borne pathogens. The patient's symptoms improved with antimicrobial therapy, further suggesting an infectious etiology. The patient's CSF showed lymphocytic pleocytosis and elevated protein, which are consistent with a chronic meningitis. The patient's symptoms and CSF findings, along with his history of immunosuppressive therapy and possible tick exposure, suggest a diagnosis of tick-borne encephalitis.\n\nDiagnosis: Tick-borne encephalitis.""
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        ""content"": ""The patient is a 63-year-old man with a history of primary membranous nephropathy who presents with fever, confusion, headache, garbled speech, fatigue, vision changes, lymphocytic pleocytosis, and an elevated protein level in the cerebrospinal fluid (CSF). The differential diagnosis for this patient includes central nervous system (CNS) infection, CNS vasculitis, CNS lymphoma, and paraneoplastic syndrome. Given the patient's history of immunosuppressive therapy for nephropathy, CNS infection is a strong possibility. However, the patient's CSF and blood cultures were negative, and he did not respond to broad-spectrum antibiotics, making infection less likely. CNS vasculitis could also present with these symptoms, but the patient's negative ANCA and normal complement levels make this less likely. CNS lymphoma could present with these symptoms, but the patient's normal imaging studies make this less likely. Paraneoplastic syndrome could also present with these symptoms, but the patient's normal PET-CT scan makes this less likely. The patient's symptoms, CSF findings, and response to immunosuppressive therapy are most consistent with autoimmune encephalitis. \n\nDiagnosis: Autoimmune Encephalitis.""
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EJMcpc1904039,Case 31-2020: A 48-Year-Old Man with Lymphoma and Abdominal Pain,"White-cell count (per μl)   6110 3370 2480
Hemoglobin (g/dl)   8.6 7.2 8.8
Hematocrit (%)   27.0 22.4 27.2
Mean corpuscular volume (fl)   112.0 112.0 109.7
Platelet count (per μl)   7000 8000 13,000
Differential count (per μl)
Neutrophils   3010 0 130
Lymphocytes   2100 4800 6370
Monocytes   700 640 1950
Eosinophils   70 160 NA
Blasts 0 1120 2400 4420
Smear morphology Toxic granulation, 
basophilic 
stippling, 
target cells, 
smudge cells, 
1+ polychrome
Smudge cells Smudge cells
Lactate dehydrogenase (U/liter) 11 10 2764 NA 2124
Alanine aminotransferase (U/liter)   142 125 121
Aspartate aminotransferase (U/liter)   227 242 224
Alkaline phosphatase (U/liter)   1667 1362 1411
Total bilirubin (mg/dl)  2.5 4.6 9.1
Direct bilirubin (mg/dl) 0.  NA 3.8 NA
Albumin (g/dl)   3.0 2.5 2.5",Disseminated cryptococcosis,Disseminated cryptococcosis,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old man with diffuse large B-cell lymphoma was evaluated in the oncology clinic of this hospital because of abdominal pain.
The patient had been generally well until 12 years before this presentation, when lymphadenopathy in the axillary and inguinal regions developed and a diagnosis of stage III follicular lymphoma was made. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone were administered and induced a clinical response; rituximab maintenance therapy was initiated.
Seven years before this presentation, recurrent disease developed; rituximab, cyclophosphamide, vincristine, and prednisone were administered. The patient again had a clinical remission, and rituximab maintenance therapy was resumed.
Two years before the current presentation, the patient transferred his oncologic care to this hospital. Swelling was noted in the right inguinal region, and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) of the chest, abdomen, and pelvis revealed extensive FDG uptake throughout the body. Biopsy of a paraaortic lymph node revealed high-grade follicular lymphoma. Salvage chemotherapy with cisplatin, gemcitabine, rituximab, and dexamethasone was administered, and the patient had an early clinical remission.
Four months later, and 20 months before the current presentation, the patient underwent autologous stem-cell transplantation after the administration of carmustine, cytarabine, etoposide, and melphalan. After transplantation, his clinical course was complicated by acute deep-vein thrombosis of the left leg; treatment with therapeutic enoxaparin sodium was initiated but was discontinued after 1 week owing to severe thrombocytopenia.
Five months later, clinical signs of lymphoma relapse were observed, and biopsy of an enlarged axillary lymph node revealed transformation to diffuse large B-cell lymphoma. The patient was subsequently treated with several therapies, including blinatumomab, chimeric antigen receptor (CAR) T cells, and pembrolizumab, none of which induced a sustained clinical response. Because of the lack of clinical response, allogeneic stem-cell transplantation was considered.
Two and a half weeks before this presentation, the patient was admitted to this hospital for severe pain in the epigastrium and bilateral inguinal regions. Laboratory studies revealed a lactate dehydrogenase level of 1560 U per liter (reference range, 110 to 210), an alanine aminotransferase level of 127 U per liter (reference range, 10 to 55), an aspartate aminotransferase level of 143 U per liter (reference range, 10 to 40), an alkaline phosphatase level of 1506 U per liter (reference range, 30 to 100), and a total bilirubin level of 2.5 mg per deciliter (reference range, 0.0 to 1.0). Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed several clustered small pulmonary nodules, progressive hepatosplenomegaly with normal-appearing bile ducts, multifocal enlarging lymph nodes, and new small-volume ascites. Oral methadone and morphine sulfate and a 5-day course of intravenous methylprednisolone were administered, resulting in alleviation of pain and improvement in liver function. The patient was discharged home on the fifth hospital day.
Two weeks after discharge, the patient was evaluated in the oncology clinic of this hospital for recurrent severe, sharp pain in the bilateral inguinal regions, as well as diffuse abdominal pain in the upper quadrants that was no longer responsive to oral analgesic agents. He also reported night sweats, decreased energy, poor appetite, nausea, and constipation. He did not have fevers, chills, headache, vision changes, shortness of breath, cough, or dysuria. Medications were acyclovir, trimethoprim-sulfamethoxazole, nystatin oral elixir, methadone, morphine sulfate, citalopram, omeprazole, simethicone, and a multivitamin, as well as lorazepam and laxatives as needed. He had no known allergies to medications.
The patient was born and raised in central Mexico and often returned to visit family. He had moved to the United States 2 years before this presentation. He lived with his wife and two adolescent daughters in an urban neighborhood in New England. He worked in the information technology industry. He had previously smoked one cigarette daily and had quit 4 years earlier; he drank one beer every other week and did not use illicit drugs. His mother had had breast cancer, and his father had had coronary artery disease, hypertension, and alcohol use disorder. His children were healthy.
On examination in the oncology clinic, the temperature was 36.7[degrees]C, the pulse 138 beats per minute, the blood pressure 123/84 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The weight was 61.5 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 20.0. He had cachexia and was in moderate distress from pain. The mucous membranes were dry, and thrush was present in the oropharynx. The abdomen was soft, with normal bowel sounds; the right and left upper quadrants were moderately tender on palpation. Painful lymphadenopathy involving the cervical, supraclavicular, and inguinal chains was present. The patient was oriented to person, place, and time, and no confusion was noted. There was no rash. Blood levels of electrolytes and results of renal function tests and urinalysis were normal. Other laboratory test results are shown in Table 1. The patient was admitted to the oncology unit of this hospital.	
Table 1 
On arrival at the oncology unit, the patient was observed to be in severe pain. Intravenous morphine and normal saline were administered. A platelet transfusion was begun. Thirty minutes later, shaking chills and diaphoresis developed. On examination, the temperature was 39.1[degrees]C, and the oxygen saturation was 85% while the patient was breathing ambient air. He was somnolent and oriented to self but not to location or time, and he had slow, nonsensical speech. Blood cultures were obtained. Oxygen, intravenous cefepime and meperidine, and oral metronidazole and acetaminophen were administered; the administration of fentanyl with a patient-controlled analgesia pump was begun for pain control. By the following morning, the patient's mental status had returned to baseline.
On the second hospital day, abdominal pain and low-grade fever persisted. Laboratory test results are shown in Table 1. Filgrastim was administered. Ultrasonography of the abdomen revealed heterogeneous liver parenchyma, diffuse thickening of the gallbladder wall, and no dilatation of the bile ducts.
Dr. Avinash Kambadakone: CT of the abdomen and pelvis (Figure 1A, 1B, and 1C), performed after the administration of intravenous contrast material, revealed multiple new, poorly circumscribed hypodense lesions throughout the liver and new bilateral pleural effusions. There was gradual reduction in the multifocal abdominopelvic lymphadenopathy and stable splenomegaly with hypodense splenic lesions. Magnetic resonance imaging (MRI) of the liver was recommended for further characterization of the lesions.	
Figure 1 
Dr. Smibert: On the third hospital day, abdominal pain and low-grade fevers persisted and intermittent episodes of somnolence and confusion, including inability to respond to questions, recurred. Laboratory studies revealed an ammonia level of 59 [mu]mol per liter (reference range, 12 to 48), a lipase level of 260 U per liter (reference range, 13 to 60), and an amylase level of 187 U per liter (reference range, 3 to 100); other laboratory test results are shown in Table 1.
Dr. Kambadakone: MRI of the liver (Figure 1D, 1E, and 1F) with cholangiopancreatography, performed after the administration of intravenous gadolinium, confirmed the presence of multiple ill-defined foci throughout the liver, with hyperintensity on T2-weighted imaging and no appreciable enhancement, and also showed focal lesions of a similar appearance throughout the spleen. There was no dilatation of the bile ducts. The imaging findings suggested the diagnostic possibility of hepatosplenic microabscesses or new lymphomatous deposits.
Dr. Smibert: A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old man with diffuse large B-cell lymphoma was evaluated in the oncology clinic of this hospital because of abdominal pain.
The patient had been generally well until 12 years before this presentation, when lymphadenopathy in the axillary and inguinal regions developed and a diagnosis of stage III follicular lymphoma was made. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone were administered and induced a clinical response; rituximab maintenance therapy was initiated.
Seven years before this presentation, recurrent disease developed; rituximab, cyclophosphamide, vincristine, and prednisone were administered. The patient again had a clinical remission, and rituximab maintenance therapy was resumed.
Two years before the current presentation, the patient transferred his oncologic care to this hospital. Swelling was noted in the right inguinal region, and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) of the chest, abdomen, and pelvis revealed extensive FDG uptake throughout the body. Biopsy of a paraaortic lymph node revealed high-grade follicular lymphoma. Salvage chemotherapy with cisplatin, gemcitabine, rituximab, and dexamethasone was administered, and the patient had an early clinical remission.
Four months later, and 20 months before the current presentation, the patient underwent autologous stem-cell transplantation after the administration of carmustine, cytarabine, etoposide, and melphalan. After transplantation, his clinical course was complicated by acute deep-vein thrombosis of the left leg; treatment with therapeutic enoxaparin sodium was initiated but was discontinued after 1 week owing to severe thrombocytopenia.
Five months later, clinical signs of lymphoma relapse were observed, and biopsy of an enlarged axillary lymph node revealed transformation to diffuse large B-cell lymphoma. The patient was subsequently treated with several therapies, including blinatumomab, chimeric antigen receptor (CAR) T cells, and pembrolizumab, none of which induced a sustained clinical response. Because of the lack of clinical response, allogeneic stem-cell transplantation was considered.
Two and a half weeks before this presentation, the patient was admitted to this hospital for severe pain in the epigastrium and bilateral inguinal regions. Laboratory studies revealed a lactate dehydrogenase level of 1560 U per liter (reference range, 110 to 210), an alanine aminotransferase level of 127 U per liter (reference range, 10 to 55), an aspartate aminotransferase level of 143 U per liter (reference range, 10 to 40), an alkaline phosphatase level of 1506 U per liter (reference range, 30 to 100), and a total bilirubin level of 2.5 mg per deciliter (reference range, 0.0 to 1.0). Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed several clustered small pulmonary nodules, progressive hepatosplenomegaly with normal-appearing bile ducts, multifocal enlarging lymph nodes, and new small-volume ascites. Oral methadone and morphine sulfate and a 5-day course of intravenous methylprednisolone were administered, resulting in alleviation of pain and improvement in liver function. The patient was discharged home on the fifth hospital day.
Two weeks after discharge, the patient was evaluated in the oncology clinic of this hospital for recurrent severe, sharp pain in the bilateral inguinal regions, as well as diffuse abdominal pain in the upper quadrants that was no longer responsive to oral analgesic agents. He also reported night sweats, decreased energy, poor appetite, nausea, and constipation. He did not have fevers, chills, headache, vision changes, shortness of breath, cough, or dysuria. Medications were acyclovir, trimethoprim-sulfamethoxazole, nystatin oral elixir, methadone, morphine sulfate, citalopram, omeprazole, simethicone, and a multivitamin, as well as lorazepam and laxatives as needed. He had no known allergies to medications.
The patient was born and raised in central Mexico and often returned to visit family. He had moved to the United States 2 years before this presentation. He lived with his wife and two adolescent daughters in an urban neighborhood in New England. He worked in the information technology industry. He had previously smoked one cigarette daily and had quit 4 years earlier; he drank one beer every other week and did not use illicit drugs. His mother had had breast cancer, and his father had had coronary artery disease, hypertension, and alcohol use disorder. His children were healthy.
On examination in the oncology clinic, the temperature was 36.7[degrees]C, the pulse 138 beats per minute, the blood pressure 123/84 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The weight was 61.5 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 20.0. He had cachexia and was in moderate distress from pain. The mucous membranes were dry, and thrush was present in the oropharynx. The abdomen was soft, with normal bowel sounds; the right and left upper quadrants were moderately tender on palpation. Painful lymphadenopathy involving the cervical, supraclavicular, and inguinal chains was present. The patient was oriented to person, place, and time, and no confusion was noted. There was no rash. Blood levels of electrolytes and results of renal function tests and urinalysis were normal. Other laboratory test results are shown in Table 1. The patient was admitted to the oncology unit of this hospital.	
Table 1 
On arrival at the oncology unit, the patient was observed to be in severe pain. Intravenous morphine and normal saline were administered. A platelet transfusion was begun. Thirty minutes later, shaking chills and diaphoresis developed. On examination, the temperature was 39.1[degrees]C, and the oxygen saturation was 85% while the patient was breathing ambient air. He was somnolent and oriented to self but not to location or time, and he had slow, nonsensical speech. Blood cultures were obtained. Oxygen, intravenous cefepime and meperidine, and oral metronidazole and acetaminophen were administered; the administration of fentanyl with a patient-controlled analgesia pump was begun for pain control. By the following morning, the patient's mental status had returned to baseline.
On the second hospital day, abdominal pain and low-grade fever persisted. Laboratory test results are shown in Table 1. Filgrastim was administered. Ultrasonography of the abdomen revealed heterogeneous liver parenchyma, diffuse thickening of the gallbladder wall, and no dilatation of the bile ducts.
Dr. Avinash Kambadakone: CT of the abdomen and pelvis (Figure 1A, 1B, and 1C), performed after the administration of intravenous contrast material, revealed multiple new, poorly circumscribed hypodense lesions throughout the liver and new bilateral pleural effusions. There was gradual reduction in the multifocal abdominopelvic lymphadenopathy and stable splenomegaly with hypodense splenic lesions. Magnetic resonance imaging (MRI) of the liver was recommended for further characterization of the lesions.	
Figure 1 
Dr. Smibert: On the third hospital day, abdominal pain and low-grade fevers persisted and intermittent episodes of somnolence and confusion, including inability to respond to questions, recurred. Laboratory studies revealed an ammonia level of 59 [mu]mol per liter (reference range, 12 to 48), a lipase level of 260 U per liter (reference range, 13 to 60), and an amylase level of 187 U per liter (reference range, 3 to 100); other laboratory test results are shown in Table 1.
Dr. Kambadakone: MRI of the liver (Figure 1D, 1E, and 1F) with cholangiopancreatography, performed after the administration of intravenous gadolinium, confirmed the presence of multiple ill-defined foci throughout the liver, with hyperintensity on T2-weighted imaging and no appreciable enhancement, and also showed focal lesions of a similar appearance throughout the spleen. There was no dilatation of the bile ducts. The imaging findings suggested the diagnostic possibility of hepatosplenic microabscesses or new lymphomatous deposits.
Dr. Smibert: A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""role"": ""assistant"",
        ""content"": ""The patient is a 48-year-old man with a history of diffuse large B-cell lymphoma who presents with abdominal pain, night sweats, decreased energy, poor appetite, nausea, and constipation. He also has cachexia, dry mucous membranes, thrush in the oropharynx, and painful lymphadenopathy. His laboratory results show elevated lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels. CT and MRI imaging reveal multiple new, poorly circumscribed hypodense lesions throughout the liver and new bilateral pleural effusions. The differential diagnosis for this patient includes lymphoma progression, infection, liver disease, and side effects from his cancer treatments. The patient's history of lymphoma and the imaging findings of multiple new lesions throughout the liver suggest lymphoma progression. However, the patient's symptoms of night sweats, decreased energy, poor appetite, nausea, and constipation, along with the presence of thrush in the oropharynx, suggest an infection. The elevated liver enzymes and bilirubin levels suggest liver disease, which could be due to lymphoma progression, infection, or side effects from his cancer treatments. The patient's history of multiple cancer treatments, including chemotherapy, autologous stem-cell transplantation, and immunotherapy, could also contribute to his symptoms and laboratory findings. Given the patient's history of lymphoma, the presence of multiple new lesions throughout the liver, and his symptoms, the most likely diagnosis is lymphoma progression.\n\nDiagnosis: Progression of diffuse large B-cell lymphoma.""
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10.1056/NEJMcpc2002420,Case 30-2020: A 54-Year-Old Man with Sudden Cardiac Arrest,"Sodium (mmol/liter)   149 149 146 147 150
Potassium (mmol/liter)   3.5‡ 2.0 2.0 3.1 3.1
Chloride (mmol/liter)   96 96 96 100 102
Carbon dioxide (mmol/liter)   6 33 30 19 20
Urea nitrogen (mg/dl)   13 14 15 18 18
Plasma creatinine (mg/dl)   1.79 1.78 1.85 2.30 2.45
Glucose (mg/dl)   319 262 211 220 58
Lactate (mmol/liter)   26.3 10.6 8.0 13.6
Hemoglobin (g/dl)   13.8 13.4 13.7
Hematocrit (%)   44.6 39.6 40.5
White-cell count (per μl)   16.88 16.98 32.53
Platelet count (per μl)   178,000 251,000 257,000
Calcium (mg/dl)   15.6 9.2 8.6 8.5
Ionized calcium (mmol/liter)   1.26 1.17 1.10
Phosphorus (mg/dl)   10.7 4.6
Total protein (g/dl) 6. .3
Albumin (g/dl)   2.9 2.6 2.2
Lactate dehydrogenase (U/liter)   744 1569
Alanine aminotransferase (U/liter)   74 83 248
Aspartate aminotransferase (U/liter)   102 176 780
N-terminal pro–B-type natriuretic pep‑
tide (pg/ml)
<900 1942
High-sensitivity troponin T (ng/liter)   1614 14,304
Creatine kinase (U/liter)   2473 9504
Creatine kinase MB (ng/ml)   149.7 338.0                                                     Venous blood gases
Fraction of inspired oxygen 1.0
pH   <6.77
Pco2 (mm Hg)   >152
Po2 (mm Hg)   43
Arterial blood gases
Fraction of inspired oxygen 1.0 0.50 0.50 0.50 0.50
pH   7.23 7.36 7.49 7.49 7.38
Pco2 (mm Hg)   76 64 45 43 35
Po2 (mm Hg)   296 89 66 76 171
Potassium, whole blood (mmol/
liter)
  1.6 1.7 1.9 2.5 2.9
Urine
Red cells (per high-power field)    
White cells (per high-power field)    
Bacteria None 1+
Toxicology tests Negative for 6-mono‚Äë
acetylmorphine, 
amphetamines, 
barbiturates, 
benzodiazepines, 
buprenorphine, 
cannabinoids, 
cocaine, metha‚Äë
done, opiates, 
oxycodone, phen‚Äë
cyclidine
Negative",Peudohyperaldosteronism suggestive of excessive licorice consumption complicated by cardiac arrest associated with ventricular fibrillation.,"Metabolic, renal, vascular, and cardiac toxic effects from apparent mineralocorticoid excess due to licorice consumption.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 54-year-old man was evaluated at this hospital after cardiac arrest associated with ventricular fibrillation.
The patient had been in his usual state of health until midday on the day of admission, when he was in a fast-food restaurant and gasped suddenly, with full-body shaking and loss of consciousness. The shaking movements ceased quickly, but he remained unresponsive. Emergency medical services personnel arrived after approximately 4 minutes, and cardiopulmonary resuscitation (CPR) was initiated. The heart rhythm was identified as ventricular fibrillation; four shocks were delivered, and the patient received intravenous naloxone, amiodarone, and a bolus of epinephrine followed by a continuous infusion. A slow, wide-complex heart rhythm with a rate of 40 beats per minute was noted, reportedly with concurrent return of mental status, but CPR had to be resumed after pulselessness recurred.
The patient arrived at this hospital 30 minutes after the initial arrest. The patient was an unresponsive, middle-aged man who had undergone mechanical CPR and had no external signs of trauma. Empirical intravenous calcium chloride, dextrose and insulin, and sodium bicarbonate were administered. In addition, vasopressin, norepinephrine, rocuronium, and ketamine were administered intravenously, and aspirin was administered rectally. Emergency intubation of the trachea was performed, and an orogastric tube, a femoral arterial catheter, and a femoral central venous catheter were placed.
Dr. Neel M. Butala: An electrocardiogram (ECG) (Figure 1A) showed uncertain atrial activity; a regular accelerated idioventricular rhythm at a rate of 70 beats per minute, with a very wide QRS complex and multifocal premature ventricular contractions; possible elevations of the ST segment in leads aVR, aVL, and V1; and the presence of U waves.	
Figure 1 
Dr. Henson: Initial laboratory test results obtained 25 minutes after the patient arrived at this hospital are shown in Table 1. Cardiac ultrasound images obtained at the bedside showed marked global left ventricular dysfunction. Spontaneous circulation was restored; the heart rate was 108 beats per minute and the blood pressure 139/92 mm Hg while the patient was receiving intravenous epinephrine and norepinephrine. A repeat ECG (Figure 1B) showed findings similar to those seen on presentation.	
Table 1 
The neurology service was consulted. A repeat examination, performed after the medications used for sedation were discontinued, revealed anisocoria and sluggishly reactive pupils (the left was 7 mm in diameter, and the right was 5 mm); corneal reflexes and response to noxious stimuli were absent. Therapeutic hypothermia was not initiated.
Dr. Laura L. Avery: Computed tomography of the head (Figure 1C), performed without the administration of intravenous contrast material, revealed preservation of differentiation between gray and white matter, without evidence of territorial infarct, intracranial hemorrhage, or mass lesions.
Dr. Butala: The patient was transferred to the cardiac catheterization laboratory, where a transaortic percutaneous ventricular assist device was placed through the femoral artery, and thereafter, the patient was weaned from epinephrine and norepinephrine. Coronary angiography (Figure 1D and 1E) revealed only minimal luminal irregularities (see Videos 1 and 2, available with the full text of this article at
NEJM.org
). Subsequent catheterization of the right and left sides of the heart revealed a right atrial pressure of 13 mm Hg, a pulmonary capillary wedge pressure of 27 mm Hg, and a left ventricular end-diastolic pressure of 30 mm Hg. The pulmonary arterial oxygen saturation was 85%.
Dr. Henson: Additional laboratory test results returned during the catheterization procedure (Table 1) were notable for a blood potassium level of 2.0 mmol per liter (normal range, 3.4 to 5.0). The patient received 60 mmol of enteral potassium chloride and 80 mmol of intravenous potassium chloride. Three hours after the patient arrived at this hospital, he was admitted to the cardiac intensive care unit (ICU), whereupon limited additional history was available from family and friends.
There was no history of chest pain, dyspnea, or symptoms of heart failure or dysrhythmia. He had a poor diet, consisting primarily of several packages of candy daily; 3 weeks earlier, he had switched the type of candy he was eating. He had no sick contacts, fever or chills, nausea, vomiting, or diarrhea.
Medical history included previous heroin use disorder and untreated hepatitis C virus infection. The patient had never had any adverse drug reactions. He worked in construction. He did not drink alcohol, he smoked one pack of cigarettes daily and had done so for 36 years, and he had reportedly been abstinent from opiates for the previous 3 years. There was no family history of cardiac, respiratory, renal, neurologic, or endocrine disease.
The temperature was 34.0[degrees]C, the heart rate 119 beats per minute, the blood pressure 81/53 mm Hg (on the percutaneous ventricular assist device), and the oxygen saturation 95% while the patient was receiving oxygen through a mechanical ventilator (fraction of inspired oxygen, 0.50; respiratory rate, 24 breaths per minute; positive end-expiratory pressure, 5 cm of water; tidal volume, 450 ml). On examination, he was unresponsive; the pupils remained sluggishly reactive and asymmetric. No cough or gag was noted, and corneal reflexes remained absent. There were no lacerations on the tongue. The heart rhythm was tachycardic and intermittently irregular, but no murmur was noted. The skin was warm, without rashes or bruises. The remainder of the examination was unremarkable.
The blood levels of thyrotropin, free thyroxine, amylase, lipase, and carboxyhemoglobin were normal; other laboratory test results are shown in Table 1. Potassium chloride (at a dose of 40 mmol) was administered intravenously.
Dr. Butala: An ECG (Figure 2A) showed sinus tachycardia with alternating left anterior fascicular block and left bundle-branch block, as well as corrected QT (QTc) prolongation.	
Figure 2 
Dr. Avery: A chest radiograph (Figure 2B) showed clear lungs, with no evidence of pneumothorax, and a normal-sized cardiac silhouette. The endotracheal tube, pulmonary-artery catheter, and percutaneous ventricular assist device were all appropriately positioned.
Dr. Butala: Transthoracic echocardiography (Figure 2C) showed normal left ventricular size but severe biventricular dysfunction, which was new relative to an outpatient study obtained 16 months earlier that had shown normal biventricular function. The percutaneous ventricular assist device was confirmed to be in an appropriate position, and there was no evidence of pericardial effusion (see Video 3).
Dr. Henson: Intravenous clevidipine was administered for elevated blood pressure. Telemetric monitoring showed frequent ventricular couplets and triplets, as well as runs of nonsustained ventricular tachycardia. Amiodarone was infused intravenously. Additional arterial blood gas measurements were obtained 2 hours after the patient arrived at the ICU (Table 1), and the patient received 60 mmol of intravenous potassium chloride, followed by an additional 40 mmol of intravenous potassium chloride 2 hours later.
Dr. Butala: A repeat ECG (Figure 2D) showed sinus tachycardia with a normal QRS duration, ventricular ectopic beat, nonspecific ST-segment and T-wave abnormalities, U waves, and QTc prolongation.
Dr. Henson: Four hours later, an additional 40 mmol of intravenous potassium chloride was administered after more test results were received. The patient's family provided additional history, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 54-year-old man was evaluated at this hospital after cardiac arrest associated with ventricular fibrillation.
The patient had been in his usual state of health until midday on the day of admission, when he was in a fast-food restaurant and gasped suddenly, with full-body shaking and loss of consciousness. The shaking movements ceased quickly, but he remained unresponsive. Emergency medical services personnel arrived after approximately 4 minutes, and cardiopulmonary resuscitation (CPR) was initiated. The heart rhythm was identified as ventricular fibrillation; four shocks were delivered, and the patient received intravenous naloxone, amiodarone, and a bolus of epinephrine followed by a continuous infusion. A slow, wide-complex heart rhythm with a rate of 40 beats per minute was noted, reportedly with concurrent return of mental status, but CPR had to be resumed after pulselessness recurred.
The patient arrived at this hospital 30 minutes after the initial arrest. The patient was an unresponsive, middle-aged man who had undergone mechanical CPR and had no external signs of trauma. Empirical intravenous calcium chloride, dextrose and insulin, and sodium bicarbonate were administered. In addition, vasopressin, norepinephrine, rocuronium, and ketamine were administered intravenously, and aspirin was administered rectally. Emergency intubation of the trachea was performed, and an orogastric tube, a femoral arterial catheter, and a femoral central venous catheter were placed.
Dr. Neel M. Butala: An electrocardiogram (ECG) (Figure 1A) showed uncertain atrial activity; a regular accelerated idioventricular rhythm at a rate of 70 beats per minute, with a very wide QRS complex and multifocal premature ventricular contractions; possible elevations of the ST segment in leads aVR, aVL, and V1; and the presence of U waves.	
Figure 1 
Dr. Henson: Initial laboratory test results obtained 25 minutes after the patient arrived at this hospital are shown in Table 1. Cardiac ultrasound images obtained at the bedside showed marked global left ventricular dysfunction. Spontaneous circulation was restored; the heart rate was 108 beats per minute and the blood pressure 139/92 mm Hg while the patient was receiving intravenous epinephrine and norepinephrine. A repeat ECG (Figure 1B) showed findings similar to those seen on presentation.	
Table 1 
The neurology service was consulted. A repeat examination, performed after the medications used for sedation were discontinued, revealed anisocoria and sluggishly reactive pupils (the left was 7 mm in diameter, and the right was 5 mm); corneal reflexes and response to noxious stimuli were absent. Therapeutic hypothermia was not initiated.
Dr. Laura L. Avery: Computed tomography of the head (Figure 1C), performed without the administration of intravenous contrast material, revealed preservation of differentiation between gray and white matter, without evidence of territorial infarct, intracranial hemorrhage, or mass lesions.
Dr. Butala: The patient was transferred to the cardiac catheterization laboratory, where a transaortic percutaneous ventricular assist device was placed through the femoral artery, and thereafter, the patient was weaned from epinephrine and norepinephrine. Coronary angiography (Figure 1D and 1E) revealed only minimal luminal irregularities (see Videos 1 and 2, available with the full text of this article at
NEJM.org
). Subsequent catheterization of the right and left sides of the heart revealed a right atrial pressure of 13 mm Hg, a pulmonary capillary wedge pressure of 27 mm Hg, and a left ventricular end-diastolic pressure of 30 mm Hg. The pulmonary arterial oxygen saturation was 85%.
Dr. Henson: Additional laboratory test results returned during the catheterization procedure (Table 1) were notable for a blood potassium level of 2.0 mmol per liter (normal range, 3.4 to 5.0). The patient received 60 mmol of enteral potassium chloride and 80 mmol of intravenous potassium chloride. Three hours after the patient arrived at this hospital, he was admitted to the cardiac intensive care unit (ICU), whereupon limited additional history was available from family and friends.
There was no history of chest pain, dyspnea, or symptoms of heart failure or dysrhythmia. He had a poor diet, consisting primarily of several packages of candy daily; 3 weeks earlier, he had switched the type of candy he was eating. He had no sick contacts, fever or chills, nausea, vomiting, or diarrhea.
Medical history included previous heroin use disorder and untreated hepatitis C virus infection. The patient had never had any adverse drug reactions. He worked in construction. He did not drink alcohol, he smoked one pack of cigarettes daily and had done so for 36 years, and he had reportedly been abstinent from opiates for the previous 3 years. There was no family history of cardiac, respiratory, renal, neurologic, or endocrine disease.
The temperature was 34.0[degrees]C, the heart rate 119 beats per minute, the blood pressure 81/53 mm Hg (on the percutaneous ventricular assist device), and the oxygen saturation 95% while the patient was receiving oxygen through a mechanical ventilator (fraction of inspired oxygen, 0.50; respiratory rate, 24 breaths per minute; positive end-expiratory pressure, 5 cm of water; tidal volume, 450 ml). On examination, he was unresponsive; the pupils remained sluggishly reactive and asymmetric. No cough or gag was noted, and corneal reflexes remained absent. There were no lacerations on the tongue. The heart rhythm was tachycardic and intermittently irregular, but no murmur was noted. The skin was warm, without rashes or bruises. The remainder of the examination was unremarkable.
The blood levels of thyrotropin, free thyroxine, amylase, lipase, and carboxyhemoglobin were normal; other laboratory test results are shown in Table 1. Potassium chloride (at a dose of 40 mmol) was administered intravenously.
Dr. Butala: An ECG (Figure 2A) showed sinus tachycardia with alternating left anterior fascicular block and left bundle-branch block, as well as corrected QT (QTc) prolongation.	
Figure 2 
Dr. Avery: A chest radiograph (Figure 2B) showed clear lungs, with no evidence of pneumothorax, and a normal-sized cardiac silhouette. The endotracheal tube, pulmonary-artery catheter, and percutaneous ventricular assist device were all appropriately positioned.
Dr. Butala: Transthoracic echocardiography (Figure 2C) showed normal left ventricular size but severe biventricular dysfunction, which was new relative to an outpatient study obtained 16 months earlier that had shown normal biventricular function. The percutaneous ventricular assist device was confirmed to be in an appropriate position, and there was no evidence of pericardial effusion (see Video 3).
Dr. Henson: Intravenous clevidipine was administered for elevated blood pressure. Telemetric monitoring showed frequent ventricular couplets and triplets, as well as runs of nonsustained ventricular tachycardia. Amiodarone was infused intravenously. Additional arterial blood gas measurements were obtained 2 hours after the patient arrived at the ICU (Table 1), and the patient received 60 mmol of intravenous potassium chloride, followed by an additional 40 mmol of intravenous potassium chloride 2 hours later.
Dr. Butala: A repeat ECG (Figure 2D) showed sinus tachycardia with a normal QRS duration, ventricular ectopic beat, nonspecific ST-segment and T-wave abnormalities, U waves, and QTc prolongation.
Dr. Henson: Four hours later, an additional 40 mmol of intravenous potassium chloride was administered after more test results were received. The patient's family provided additional history, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with cardiac arrest associated with ventricular fibrillation. The patient's ECG showed a very wide QRS complex and multifocal premature ventricular contractions, which are indicative of ventricular arrhythmias. The patient's blood potassium level was significantly low, which can cause ventricular arrhythmias and cardiac arrest. The patient's diet was poor and consisted primarily of candy, which can lead to electrolyte imbalances, including hypokalemia. The patient's cardiac ultrasound showed marked global left ventricular dysfunction, which can be caused by severe electrolyte imbalances. Therefore, the patient's cardiac arrest was likely caused by severe hypokalemia resulting from his poor diet.\n\nDiagnosis: Cardiac arrest due to severe hypokalemia.""
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        ""content"": ""The patient is a 54-year-old man who presented with cardiac arrest associated with ventricular fibrillation. The differential diagnosis for this patient includes myocardial infarction, electrolyte imbalance, drug overdose, and hypoxia. The patient's ECG showed a wide QRS complex and multifocal premature ventricular contractions, which could be indicative of myocardial infarction. However, coronary angiography revealed only minimal luminal irregularities, making myocardial infarction less likely. The patient's history of heroin use disorder raises the possibility of drug overdose, but he had reportedly been abstinent from opiates for the previous 3 years. The patient's blood potassium level was notably low at 2.0 mmol per liter, indicating a severe electrolyte imbalance. This could potentially cause ventricular fibrillation and cardiac arrest. The patient's diet was reported to be poor, consisting primarily of several packages of candy daily. This could contribute to the electrolyte imbalance. The patient's blood oxygen saturation was 85%, which is lower than normal but not low enough to cause hypoxia. Therefore, the most likely diagnosis for this patient is severe hypokalemia caused by poor diet.\n\nDiagnosis: Severe hypokalemia.""
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}",Severe hypokalemia,N
10.1056/NEJMcpc2004982,Case 29-2020: A 66-Year-Old Man with Fever and Shortness of Breath after Liver Transplantation,"White-cell count (per μl)   5390 8910 13
Differential count (per μl)
Neutrophils   4540 8150
Lymphocytes   470 150
Monocytes   380 300
Prothrombin time (sec)   13.1 14.9 16
Prothrombin-time international normalized 
ratio
  1.0 1.2 16
d-dimer (ng/ml)   1074 2977 16
Fibrinogen (mg/dl) 15 0 580 1134 15
Ferritin (μg/liter) 2 00 1361 5798 11
Erythrocyte sedimentation rate (mm/hr)   23 124 15
C-reactive protein (mg/liter)  .0 126.5 240.7 12
Procalcitonin (ng/ml) 0.00–0.08 0.24 0.49 12
Creatinine (mg/dl)   2.0 2.8 6
Aspartate aminotransferase (U/liter)   65 65 1
Alanine aminotransferase (U/liter)   60 75 8
Lactate dehydrogenase (U/liter) 11 10 238 365 8
Creatine kinase (U/liter)   247 339 2
High-sensitivity troponin T (ng/liter)   37 45 8
Triglycerides (mg/dl)   206
Interleukin-6 (pg/ml) <1.8 24.7 4
Mycobacterium tuberculosis interferon-γ 
release assay
Negative Negative Negative
Hepatitis B virus core antibody Negative Positive Positive
Hepatitis B virus surface antigen Negative Positive Positive
Cytomegalovirus IgG Negative Positive
Cytomegalovirus DNA Negative Negative
Epstein–Barr virus viral capsid antigen IgG Negative Positive
Influenza A virus DNA Negative Negative
Influenza B virus DNA Negative Negative
Respiratory syncytial virus DNA Negative Negative
Legionella pneumophila serogroup 1 urinary 
antigen
Negative Negative",Severe acute respiratory syndrome coronavirus 2 infection.,Severe acute respiratory syndrome coronavirus 2 infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 66-year-old man who had undergone orthotopic liver transplantation because of end-stage liver disease was admitted to this hospital because of fever and cough during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Two days before this admission, fever, chills, and diffuse myalgias developed. The patient also noted a dry cough and nausea and that he had reduced his fluid intake. On the day of admission, the patient learned that his sister had received a diagnosis of Covid-19, and he was concerned that his symptoms might also be caused by infection with SARS-CoV-2, prompting him to present to a neighborhood health center.
At the health center, the patient reported mild dyspnea. He appeared comfortable, with unlabored breathing. The temperature was 37.8[degrees]C, the pulse 125 beats per minute, the blood pressure 127/78 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. Auscultation of the lungs revealed normal breath sounds. Further evaluation in the emergency department of this hospital was recommended.
On arrival at the emergency department, the patient reported ongoing cough and nausea but no chest pain, abdominal pain, vomiting, or diarrhea. He had a history of hypertension, diabetes, hyperlipidemia, obesity, peripheral neuropathy, chronic kidney disease, and end-stage liver disease due to alcohol use disorder and hepatitis B virus infection. Twenty-two months earlier, renal replacement therapy had been initiated for worsening renal function due to the hepatorenal syndrome, and shortly after, the patient had undergone orthotopic liver transplantation. Combined liver and kidney transplantation had been planned, but the donor kidney was unsuitable for transplantation because of extensive dissection of the renal artery. After the liver transplantation, the patient's renal function improved, and renal replacement therapy was discontinued. Histopathological examination of tissue from the explanted native liver revealed moderately differentiated hepatocellular carcinoma without evidence of intravascular invasion.
Current medications included tacrolimus, mycophenolate, amlodipine, doxazosin, gabapentin, omeprazole, ursodiol, and magnesium oxide. There were no known allergies. The patient was widowed and lived with his sister and several friends in an apartment in an urban area of New England. He was born in Central America and had immigrated to the United States three decades earlier. He had smoked tobacco in the past but had quit 14 years earlier. He had stopped drinking alcohol 3 years earlier; during periods of heavy drinking, he had used cocaine and marijuana occasionally.
On examination, the patient appeared comfortable. The temperature was 38.0[degrees]C, the pulse 99 beats per minute, the blood pressure 134/73 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 94% while he was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.1. The respiratory effort and breath sounds were normal, as was the remainder of the physical examination. Nucleic acid testing of a nasopharyngeal swab for influenza viruses and respiratory syncytial virus was negative. A nasopharyngeal swab for nucleic acid testing for SARS-CoV-2 RNA was obtained. Urinalysis revealed a pH of 5.5, a specific gravity of 1.008, 1+ blood, and 1+ protein. A urine test for legionella antigen was negative. Gram's staining of a sputum specimen revealed rare polymorphonuclear leukocytes and few mixed gram-positive and gram-negative organisms with no specific type predominating; sputum and blood samples were obtained for culture. Other laboratory test results are shown in Table 1. An electrocardiogram showed sinus tachycardia and nonspecific ST-segment and T-wave abnormalities that were unchanged from a study that had been performed 6 months earlier; the corrected QT interval was 424 msec.	
Table 1 
Dr. Eric W. Zhang: Chest radiography (Figure 1A) revealed low lung volumes with patchy, confluent airspace opacities in the mid-to-lower lungs that were more prominent on the left side than on the right side, with peripheral predominance. There were no radiographically significant pleural effusions.	
Figure 1 
Dr. Roberts: Intravenous normal saline, intravenous ceftriaxone, and oral azithromycin were administered, and the patient was admitted to the hospital. On admission, the oxygen saturation was 88% while he was breathing ambient air, and auscultation of the lungs revealed coarse crackles. Supplemental oxygen was administered through a nasal cannula at a rate of 2 liters per minute. Amlodipine and doxazosin were discontinued. The next morning, the polymerase-chain-reaction test for SARS-CoV-2 RNA showed a positive result. Atorvastatin, oral prednisone, and hydroxychloroquine were initiated, and the dose of mycophenolate was decreased.
During the next 2 days, the temperature increased to 39.2[degrees]C. Chills, myalgias, nausea, and cough continued; dyspnea increased; and headache, diarrhea, and occasional vomiting developed. Blood cultures obtained at the time of admission remained negative, and the sputum culture grew normal respiratory flora. Acetaminophen and ondansetron were administered, and the rate of supplemental oxygen was increased to 6 liters per minute. The patient was placed in the prone position in bed.
On the fourth hospital day, the serum level of interleukin-6 was 24.6 pg per milliliter (reference value, <1.8); the levels of inflammatory markers and other laboratory test results are shown in Table 1. On the morning of the fifth hospital day, the oxygen saturation fell below 90% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 6 liters per minute. The patient was unable to speak in full sentences because of dyspnea, and auscultation of the lungs revealed decreased air entry.
Dr. Zhang: Chest radiography (Figure 1B) revealed low lung volumes with increased diffuse multifocal airspace opacities. There were no radiographically significant pleural effusions.
Dr. Roberts: Supplemental oxygen was administered through a nonrebreather face mask at a rate of 15 liters per minute. The patient was transferred to the medical intensive care unit (ICU), the trachea was intubated, and mechanical ventilation was initiated. On admission to the ICU, the patient was enrolled in a placebo-controlled trial of the interleukin-6 receptor antagonist sarilumab (ClinicalTrials.gov number, NCT04315298).
Management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 66-year-old man who had undergone orthotopic liver transplantation because of end-stage liver disease was admitted to this hospital because of fever and cough during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Two days before this admission, fever, chills, and diffuse myalgias developed. The patient also noted a dry cough and nausea and that he had reduced his fluid intake. On the day of admission, the patient learned that his sister had received a diagnosis of Covid-19, and he was concerned that his symptoms might also be caused by infection with SARS-CoV-2, prompting him to present to a neighborhood health center.
At the health center, the patient reported mild dyspnea. He appeared comfortable, with unlabored breathing. The temperature was 37.8[degrees]C, the pulse 125 beats per minute, the blood pressure 127/78 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. Auscultation of the lungs revealed normal breath sounds. Further evaluation in the emergency department of this hospital was recommended.
On arrival at the emergency department, the patient reported ongoing cough and nausea but no chest pain, abdominal pain, vomiting, or diarrhea. He had a history of hypertension, diabetes, hyperlipidemia, obesity, peripheral neuropathy, chronic kidney disease, and end-stage liver disease due to alcohol use disorder and hepatitis B virus infection. Twenty-two months earlier, renal replacement therapy had been initiated for worsening renal function due to the hepatorenal syndrome, and shortly after, the patient had undergone orthotopic liver transplantation. Combined liver and kidney transplantation had been planned, but the donor kidney was unsuitable for transplantation because of extensive dissection of the renal artery. After the liver transplantation, the patient's renal function improved, and renal replacement therapy was discontinued. Histopathological examination of tissue from the explanted native liver revealed moderately differentiated hepatocellular carcinoma without evidence of intravascular invasion.
Current medications included tacrolimus, mycophenolate, amlodipine, doxazosin, gabapentin, omeprazole, ursodiol, and magnesium oxide. There were no known allergies. The patient was widowed and lived with his sister and several friends in an apartment in an urban area of New England. He was born in Central America and had immigrated to the United States three decades earlier. He had smoked tobacco in the past but had quit 14 years earlier. He had stopped drinking alcohol 3 years earlier; during periods of heavy drinking, he had used cocaine and marijuana occasionally.
On examination, the patient appeared comfortable. The temperature was 38.0[degrees]C, the pulse 99 beats per minute, the blood pressure 134/73 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 94% while he was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.1. The respiratory effort and breath sounds were normal, as was the remainder of the physical examination. Nucleic acid testing of a nasopharyngeal swab for influenza viruses and respiratory syncytial virus was negative. A nasopharyngeal swab for nucleic acid testing for SARS-CoV-2 RNA was obtained. Urinalysis revealed a pH of 5.5, a specific gravity of 1.008, 1+ blood, and 1+ protein. A urine test for legionella antigen was negative. Gram's staining of a sputum specimen revealed rare polymorphonuclear leukocytes and few mixed gram-positive and gram-negative organisms with no specific type predominating; sputum and blood samples were obtained for culture. Other laboratory test results are shown in Table 1. An electrocardiogram showed sinus tachycardia and nonspecific ST-segment and T-wave abnormalities that were unchanged from a study that had been performed 6 months earlier; the corrected QT interval was 424 msec.	
Table 1 
Dr. Eric W. Zhang: Chest radiography (Figure 1A) revealed low lung volumes with patchy, confluent airspace opacities in the mid-to-lower lungs that were more prominent on the left side than on the right side, with peripheral predominance. There were no radiographically significant pleural effusions.	
Figure 1 
Dr. Roberts: Intravenous normal saline, intravenous ceftriaxone, and oral azithromycin were administered, and the patient was admitted to the hospital. On admission, the oxygen saturation was 88% while he was breathing ambient air, and auscultation of the lungs revealed coarse crackles. Supplemental oxygen was administered through a nasal cannula at a rate of 2 liters per minute. Amlodipine and doxazosin were discontinued. The next morning, the polymerase-chain-reaction test for SARS-CoV-2 RNA showed a positive result. Atorvastatin, oral prednisone, and hydroxychloroquine were initiated, and the dose of mycophenolate was decreased.
During the next 2 days, the temperature increased to 39.2[degrees]C. Chills, myalgias, nausea, and cough continued; dyspnea increased; and headache, diarrhea, and occasional vomiting developed. Blood cultures obtained at the time of admission remained negative, and the sputum culture grew normal respiratory flora. Acetaminophen and ondansetron were administered, and the rate of supplemental oxygen was increased to 6 liters per minute. The patient was placed in the prone position in bed.
On the fourth hospital day, the serum level of interleukin-6 was 24.6 pg per milliliter (reference value, <1.8); the levels of inflammatory markers and other laboratory test results are shown in Table 1. On the morning of the fifth hospital day, the oxygen saturation fell below 90% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 6 liters per minute. The patient was unable to speak in full sentences because of dyspnea, and auscultation of the lungs revealed decreased air entry.
Dr. Zhang: Chest radiography (Figure 1B) revealed low lung volumes with increased diffuse multifocal airspace opacities. There were no radiographically significant pleural effusions.
Dr. Roberts: Supplemental oxygen was administered through a nonrebreather face mask at a rate of 15 liters per minute. The patient was transferred to the medical intensive care unit (ICU), the trachea was intubated, and mechanical ventilation was initiated. On admission to the ICU, the patient was enrolled in a placebo-controlled trial of the interleukin-6 receptor antagonist sarilumab (ClinicalTrials.gov number, NCT04315298).
Management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with fever, chills, diffuse myalgias, dry cough, and nausea, which are all symptoms consistent with COVID-19. He also had a history of close contact with a confirmed COVID-19 case (his sister). His symptoms did not improve and he developed increased dyspnea. A nasopharyngeal swab for nucleic acid testing for SARS-CoV-2 RNA was obtained and showed a positive result. His condition worsened, requiring supplemental oxygen and eventually intubation and mechanical ventilation. \n\nCOVID-19 (caused by SARS-CoV-2)""
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        ""content"": ""The patient is a 66-year-old man with a history of liver transplantation, hypertension, diabetes, hyperlipidemia, obesity, peripheral neuropathy, chronic kidney disease, and end-stage liver disease due to alcohol use disorder and hepatitis B virus infection. He presents with fever, chills, diffuse myalgias, dry cough, and nausea. He also has a known exposure to a confirmed case of COVID-19. The differential diagnosis for this patient includes COVID-19, influenza, other respiratory viral infections, bacterial pneumonia, and other non-infectious causes of fever and respiratory symptoms such as drug fever or malignancy. However, given the patient's known exposure to a confirmed case of COVID-19, his symptoms, and the positive result of the polymerase-chain-reaction test for SARS-CoV-2 RNA, the diagnosis of COVID-19 is most likely. \n\nDiagnosis: COVID-19.""
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10.1056/NEJMcpc2004981,Case 28-2020: A 64-Year-Old Man with Intrusive Thoughts and Fear of Being Poisoned,,Post-traumatic stress disorder and major depressive disorder in the context of culturally and religiously derived beliefs and behaviors.,"Post-traumatic stress disorder and major depressive disorder in the context of culturally and religiously derived beliefs and behaviors, with an indication to rule out psychotic features.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old Haitian-American man was evaluated at the geriatric psychiatry clinic of this hospital for chronic depression, intrusive thoughts, and fear of being poisoned.
During the evaluation, the patient described his mood as ""not that good."" He reported depression, which he rated as 4 on a scale of 0 to 10 (with 10 indicating the most severe depression). He had been having an ongoing ""depressive episode"" during the past 3 months, which had led him to call in sick to work frequently. He had passive suicidal ideation, questioning whether life was worth living; however, he had no specific intent or plan and no thoughts of harming other people. The patient had a history of nightmares, but they had not occurred during the past 3 months. In the 3 years before this evaluation, his startle response had been increased and flashbacks frequently occurred; however, at the time of the evaluation, his startle response was reduced and there were no flashbacks. He reported that women had attempted to poison his coffee. There were no auditory or visual hallucinations. He reported limited energy, difficulty initiating sleep, repeated early morning awakenings, and anorexia. There was no weight loss, difficulty concentrating, or history of headaches, seizure, or head trauma.
The patient's medical history included diabetes, dyslipidemia, hypertension, seasonal allergies, mild intermittent asthma, eczema, and chronic lower back pain associated with a motor vehicle accident that had occurred 20 years earlier. Medications included bupropion, quetiapine, aspirin, atorvastatin, ezetimibe, amlodipine, fosinopril, hydrochlorothiazide, metformin, and vitamins B12 and D3, as well as fexofenadine, naproxen, sildenafil, and inhaled albuterol as needed. Adverse drug effects included dry and painful mouth with paroxetine, reduced libido with paroxetine and citalopram, orthostatic hypotension and falls with prazosin, nausea and vomiting with lisinopril, and elevated aminotransferase levels with statins.
The patient had a family history of dyslipidemia; his brother had died of premature myocardial infarction, and his father had undergone coronary-artery bypass grafting. He had an adult child, who was healthy. There was no history of neuropsychiatric disease or substance use disorder in first-degree relatives, but male maternal cousins had major depressive disorder and schizophrenia. He worked full-time as a counselor. He visited a psychic every few weeks and was undergoing training to become a psychic and read tarot cards. He had formerly smoked a few cigarettes daily and had quit smoking when he was 30 years of age. He drank one alcoholic beverage on weekend nights and did not use illicit drugs.
The patient grew up in Haiti. His parents were devout Catholics, but many community members and relatives observed Vodou and Santeria beliefs and also practiced tarot card reading; the patient and his siblings began following Vodou and Santeria practices during adolescence. In his early life, the patient witnessed an act of police brutality in which a community member was killed, as well as the poisoning of colleagues of his father, who was a government employee. In his early adulthood, the patient immigrated to the United States. He lived in an urban area of New England, where he completed college and then worked as a counselor. He reported that he had experienced recurrent discrimination by female supervisors during his employment. In his early years of working, he encountered financial difficulties and was evicted from his apartment. During a 2-month period of homelessness, he became a victim of sexual and physical assault and subsequently had depressive symptoms, flashbacks, nightmares, and intrusive thoughts of the assault. He reported that he had not had any psychiatric symptoms before the assault.
The patient was married for a brief period and then divorced. He reported that his ex-wife had ""put a Vodou curse on me"" and that he had traveled to Haiti to have the curse removed but ""the damage cannot be undone."" For decades, he feared that female coworkers would try to poison him. For this reason, he did not drink coffee that had been unattended in the office, did not accept offers from coworkers to bring him coffee from a local shop, and avoided eating with colleagues. He felt that people at work did not like him. He described extreme self-consciousness and was concerned that people in either a professional or social setting would see ""discoloration"" when they looked at his face.
In his early adulthood, the patient had sought weekly therapy at another hospital because of depressive symptoms, intrusive thoughts, and nightmares. Four years before the current consultation, and again 1 year later and 18 months after that, he sought care at psychiatry clinics at other hospitals. Meanwhile, he continued to receive care from the same therapist for approximately three decades.
Additional history was obtained from the patient's therapist. The persecutory beliefs had been long-standing, occurring over a period of decades; they became more prominent when depressive symptoms were more active, but they were still present during periods of euthymia. The therapist observed that the patient's persecutory beliefs affected interpersonal relationships and led to the feeling of isolation at work.
The patient had undergone multiple trials of psychopharmacologic medications for the treatment of recurrent major depressive episodes, which would occur approximately two times each year and last for several weeks to months. These medications included nortriptyline, fluoxetine, paroxetine, sertraline, venlafaxine, citalopram, escitalopram, bupropion, and valproic acid. He had tried prazosin, which decreased the frequency of nightmares but was discontinued owing to orthostatic hypotension. He had undergone EMDR (eye movement, desensitization, and reprocessing) therapy, but nightmares occurred up to three times per month and intrusive thoughts of the sexual trauma occurred daily. Olanzapine and aripiprazole did not reduce paranoid thoughts; quetiapine had a modestly beneficial effect.
On examination, the patient was a well-groomed older man with no abnormal facial features. His posture and gait were normal. He was calm and cooperative, with normal eye contact and speech of an appropriate rate and volume. He was oriented to time, place, and situation, with intact attentiveness and ability to recall autobiographical and historical information. His mood was described as mildly sad and anxious with a constricted affect. The remainder of the physical examination was normal.
On laboratory testing performed at another hospital during the 6 months before the current evaluation, the complete blood count and results of renal-function tests were normal, as were levels of electrolytes, thyrotropin, and folate. The glucose level was 131 mg per deciliter (7.3 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). The glycated hemoglobin level (7.0%; reference range, 4.3 to 6.4) had increased from a level of 6.4% obtained 6 months earlier. An electrocardiogram obtained 4 months before the current evaluation showed sinus rhythm with a normal corrected QT interval.
Diagnostic and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old Haitian-American man was evaluated at the geriatric psychiatry clinic of this hospital for chronic depression, intrusive thoughts, and fear of being poisoned.
During the evaluation, the patient described his mood as ""not that good."" He reported depression, which he rated as 4 on a scale of 0 to 10 (with 10 indicating the most severe depression). He had been having an ongoing ""depressive episode"" during the past 3 months, which had led him to call in sick to work frequently. He had passive suicidal ideation, questioning whether life was worth living; however, he had no specific intent or plan and no thoughts of harming other people. The patient had a history of nightmares, but they had not occurred during the past 3 months. In the 3 years before this evaluation, his startle response had been increased and flashbacks frequently occurred; however, at the time of the evaluation, his startle response was reduced and there were no flashbacks. He reported that women had attempted to poison his coffee. There were no auditory or visual hallucinations. He reported limited energy, difficulty initiating sleep, repeated early morning awakenings, and anorexia. There was no weight loss, difficulty concentrating, or history of headaches, seizure, or head trauma.
The patient's medical history included diabetes, dyslipidemia, hypertension, seasonal allergies, mild intermittent asthma, eczema, and chronic lower back pain associated with a motor vehicle accident that had occurred 20 years earlier. Medications included bupropion, quetiapine, aspirin, atorvastatin, ezetimibe, amlodipine, fosinopril, hydrochlorothiazide, metformin, and vitamins B12 and D3, as well as fexofenadine, naproxen, sildenafil, and inhaled albuterol as needed. Adverse drug effects included dry and painful mouth with paroxetine, reduced libido with paroxetine and citalopram, orthostatic hypotension and falls with prazosin, nausea and vomiting with lisinopril, and elevated aminotransferase levels with statins.
The patient had a family history of dyslipidemia; his brother had died of premature myocardial infarction, and his father had undergone coronary-artery bypass grafting. He had an adult child, who was healthy. There was no history of neuropsychiatric disease or substance use disorder in first-degree relatives, but male maternal cousins had major depressive disorder and schizophrenia. He worked full-time as a counselor. He visited a psychic every few weeks and was undergoing training to become a psychic and read tarot cards. He had formerly smoked a few cigarettes daily and had quit smoking when he was 30 years of age. He drank one alcoholic beverage on weekend nights and did not use illicit drugs.
The patient grew up in Haiti. His parents were devout Catholics, but many community members and relatives observed Vodou and Santeria beliefs and also practiced tarot card reading; the patient and his siblings began following Vodou and Santeria practices during adolescence. In his early life, the patient witnessed an act of police brutality in which a community member was killed, as well as the poisoning of colleagues of his father, who was a government employee. In his early adulthood, the patient immigrated to the United States. He lived in an urban area of New England, where he completed college and then worked as a counselor. He reported that he had experienced recurrent discrimination by female supervisors during his employment. In his early years of working, he encountered financial difficulties and was evicted from his apartment. During a 2-month period of homelessness, he became a victim of sexual and physical assault and subsequently had depressive symptoms, flashbacks, nightmares, and intrusive thoughts of the assault. He reported that he had not had any psychiatric symptoms before the assault.
The patient was married for a brief period and then divorced. He reported that his ex-wife had ""put a Vodou curse on me"" and that he had traveled to Haiti to have the curse removed but ""the damage cannot be undone."" For decades, he feared that female coworkers would try to poison him. For this reason, he did not drink coffee that had been unattended in the office, did not accept offers from coworkers to bring him coffee from a local shop, and avoided eating with colleagues. He felt that people at work did not like him. He described extreme self-consciousness and was concerned that people in either a professional or social setting would see ""discoloration"" when they looked at his face.
In his early adulthood, the patient had sought weekly therapy at another hospital because of depressive symptoms, intrusive thoughts, and nightmares. Four years before the current consultation, and again 1 year later and 18 months after that, he sought care at psychiatry clinics at other hospitals. Meanwhile, he continued to receive care from the same therapist for approximately three decades.
Additional history was obtained from the patient's therapist. The persecutory beliefs had been long-standing, occurring over a period of decades; they became more prominent when depressive symptoms were more active, but they were still present during periods of euthymia. The therapist observed that the patient's persecutory beliefs affected interpersonal relationships and led to the feeling of isolation at work.
The patient had undergone multiple trials of psychopharmacologic medications for the treatment of recurrent major depressive episodes, which would occur approximately two times each year and last for several weeks to months. These medications included nortriptyline, fluoxetine, paroxetine, sertraline, venlafaxine, citalopram, escitalopram, bupropion, and valproic acid. He had tried prazosin, which decreased the frequency of nightmares but was discontinued owing to orthostatic hypotension. He had undergone EMDR (eye movement, desensitization, and reprocessing) therapy, but nightmares occurred up to three times per month and intrusive thoughts of the sexual trauma occurred daily. Olanzapine and aripiprazole did not reduce paranoid thoughts; quetiapine had a modestly beneficial effect.
On examination, the patient was a well-groomed older man with no abnormal facial features. His posture and gait were normal. He was calm and cooperative, with normal eye contact and speech of an appropriate rate and volume. He was oriented to time, place, and situation, with intact attentiveness and ability to recall autobiographical and historical information. His mood was described as mildly sad and anxious with a constricted affect. The remainder of the physical examination was normal.
On laboratory testing performed at another hospital during the 6 months before the current evaluation, the complete blood count and results of renal-function tests were normal, as were levels of electrolytes, thyrotropin, and folate. The glucose level was 131 mg per deciliter (7.3 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). The glycated hemoglobin level (7.0%; reference range, 4.3 to 6.4) had increased from a level of 6.4% obtained 6 months earlier. An electrocardiogram obtained 4 months before the current evaluation showed sinus rhythm with a normal corrected QT interval.
Diagnostic and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Delusional Disorder, Persecutory Type. The patient's long-standing belief that he is being poisoned, despite lack of evidence, and the fact that these beliefs persist even during periods of euthymia, suggest a delusional disorder. The specific fear of being poisoned indicates the persecutory type of this disorder. His depressive symptoms and history of trauma suggest comorbid depression and post-traumatic stress disorder.""
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        ""content"": ""The patient has a history of chronic depression, intrusive thoughts, and fear of being poisoned. He has a history of trauma, including witnessing police brutality and being a victim of sexual and physical assault. He also has a history of paranoia, believing that women have tried to poison his coffee and that his ex-wife put a curse on him. His symptoms have persisted despite multiple trials of psychopharmacologic medications. These symptoms, along with his history, suggest a diagnosis of Post-Traumatic Stress Disorder (PTSD) with paranoid features. PTSD is a disorder that can develop after a person has experienced or witnessed a traumatic event. Symptoms can include intrusive thoughts, nightmares, and changes in emotional reactions. Paranoid features can also be present in PTSD, as seen in this patient's fear of being poisoned and belief in a curse. \n\nDiagnosis: Post-Traumatic Stress Disorder (PTSD) with paranoid features.""
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        ""content"": ""The patient is a 64-year-old man presenting with chronic depression, intrusive thoughts, and fear of being poisoned. He has a history of trauma, including witnessing police brutality and being a victim of sexual and physical assault. He also has a history of perceived discrimination and persecution at work and believes that his ex-wife has put a curse on him. He has no history of hallucinations, but does have a history of nightmares and flashbacks, which have decreased in frequency. His symptoms have persisted for decades and have been resistant to multiple trials of medication. The differential diagnosis includes major depressive disorder, post-traumatic stress disorder (PTSD), and delusional disorder. His depressive symptoms, including low mood, anhedonia, and passive suicidal ideation, are consistent with major depressive disorder. His history of trauma, nightmares, flashbacks, and increased startle response are consistent with PTSD. However, his long-standing, fixed belief that he is being poisoned, which is not based in reality and is not due to cultural beliefs, is consistent with delusional disorder, persecutory type. Given the chronicity and resistance to treatment of his symptoms, as well as the significant impact on his interpersonal relationships and work, the most likely diagnosis is delusional disorder, persecutory type.\n\nDiagnosis: Delusional disorder, persecutory type.""
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10.1056/NEJMcpc1913472,"Case 27-2020: A 53-Year-Old Woman with Headache and Gait Imbalance
","Hemoglobin (g/dl)   13.9
Hematocrit (%)   42.9
Platelet count (per μl)   232,000
White-cell count (per μl)   12,460
Differential count (per μl)
Neutrophils   11,101
Lymphocytes   685
Monocytes   560
Eosinophils   0
Metamyelocytes 0 112
Urine
Color Yellow Yellow
Clarity Clear Cloudy
pH   7.0
Specific gravity   1.021
Protein Negative 1+
Glucose Negative Negative
Ketones Negative Trace
Bilirubin Negative Negative
Nitrite Negative Negative
Leukocyte esterase Negative 3+
Red cells (per high-power field)    
Leukocytes (per high-power field)    
Bacteria None 2+                                                                                                                HIV-negative with a false positive serologic screening test
HIV-1–positive with “elite controller” status and slow clinical progression
HIV-1–positive with a rare HIV-1 group (N, O, or P), HIV-1 group M subtype, 
or circulating recombinant form that is not detected by current HIV-1 viral 
load tests
HIV-negative with idiopathic CD4+ T-cell lymphopenia
HIV-1–positive with surreptitious use of antiretroviral therapy
Preanalytical error (sample mix-up)
HIV-2–positive",Human immunodeficiency virus type 2 infection and cerebral toxoplasmosis.,Toxoplasma gondii encephalitis in the context of human immunodeficiency virus type 2 infection and associated acquired immunodeficiency syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 53-year-old woman was transferred to this hospital because of progressive headache, gait instability, and weight loss.
Approximately 2 months before the patient's evaluation at this hospital, vertigo developed and resolved spontaneously. One day before evaluation at this hospital, she sought care at another hospital for recurrent dizziness and difficulty walking. The temperature was 36.4[degrees]C, the pulse 86 beats per minute, the blood pressure 170/105 mm Hg, the respiratory rate 15 breaths per minute, and the oxygen saturation 97% while she was breathing ambient air. The patient was alert and oriented, with slow speech, bilateral end-point horizontal nystagmus, and mild dysmetria on the right side on finger-nose-finger testing. Strength and sensory function were normal. She had difficulty maintaining a stable stance; her gait was narrow-based and described as ""slow and cautious."" The remainder of the examination was normal.
Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, showed an area of ill-defined hypoattenuation that was consistent with vasogenic edema in the right cerebellar hemisphere, as well as regions of white-matter hypoattenuation in both cerebellar hemispheres. Aspirin and atorvastatin were administered.
Dr. R. Gilberto Gonzalez: Magnetic resonance imaging (MRI) of the head (Figure 1), performed before and after the administration of intravenous contrast material, revealed an enhancing intraaxial lesion, measuring 2.0 cm by 1.8 cm by 1.7 cm, in the right inferior cerebellar hemisphere. The lesion had internal signal hypointensity that was indicative of necrosis on T1-weighted imaging, as well as surrounding signal hyperintensity that was suggestive of vasogenic edema on T2-weighted imaging. There was local mass effect with effacement of the overlying cerebellar fissures and the fourth ventricle. There was also an enhancing leptomeningeal lesion, measuring 4 mm in diameter, along the left medial frontal lobe in the left superior frontal gyrus, with possible leptomeningeal extension. The lesion was characterized by internal and surrounding signal hyperintensity on T2-weighted imaging.	
Figure 1 
Dr. Rosenberg: Intravenous dexamethasone, amlodipine, and labetalol were administered. The patient was transferred to this hospital for specialized neurosurgical consultation.
On evaluation at this hospital, review of systems was notable for malaise and lethargy, as well as unintentional weight loss of 15 kg during the past year. The patient also reported an increase in urinary frequency without hematuria, dysuria, or flank pain. She had no fever, chills, sinus pain, dyspnea, cough, abdominal pain, diarrhea, nausea, or vomiting. She had a history of hypertension and hemorrhagic stroke, which had led to a craniotomy on the right side for evacuation of a ""blood clot"" 13 years before the current evaluation, with no reported neurologic deficits.
The patient reported that, during the admission for craniotomy, she was told that she had human immunodeficiency virus (HIV) infection and was treated with an unknown antiretroviral therapy (ART) regimen; she could not recall the medications included in the regimen. In addition, she reported that, several years later, further testing revealed that an error had been made and she did not have HIV infection. She reported that ART medications were discontinued at least 3 years before the current evaluation.
The patient did not have a history of opportunistic infections or cancer. Three years earlier, a Mantoux tuberculin skin test had been negative. One week earlier, a mammogram had been normal. She had never undergone a colonoscopy or a Papanicolaou test.
The patient was born in Ivory Coast, West Africa, and had been living in the United States for more than 20 years. She reported no recent travel. She lived with her children and did not smoke tobacco, drink alcohol, or use illicit drugs. She was divorced and not sexually active; in her lifetime, she had had one male sexual partner. Her ex-husband and one of her children reportedly had tested negative for HIV. Her father had had a myocardial infarction in his 60s; her mother and sisters were healthy. The patient had not been taking any medications at home before this illness and had no known allergies to medications.
On physical examination, the temperature was 36.9[degrees]C, the blood pressure 165/99 mm Hg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 22.5. The patient was comfortable, alert, and oriented. Her speech was clear, with intact naming and repetition. Her pupils were equal and reactive to light, extraocular movements were intact, and visual fields were full in response to confrontation. She had mild right esotropia and no nystagmus. Her face was symmetric, but there was mild deviation of the tongue to the left. Results of other cranial-nerve testing were normal. Finger-nose-finger testing revealed subtle dysmetria that was greater on the right side than on the left side; there was no dysdiadochokinesia or intention tremor. Her stance was approximately shoulder-width. Her balance was impaired, and her gait was unsteady and ataxic. Psychomotor slowing was present, and the Romberg sign was absent. An evaluation of power, bulk, tone, sensation, and deep-tendon reflexes was normal. She had alopecia and oral thrush. The remainder of the examination was normal. The patient was admitted to the hospital for further evaluation and treatment.
Results of tests of renal, liver, and thyroid function were normal, as were blood levels of electrolytes, vitamin B12, and glycated hemoglobin. An HIV screening test for the detection of antibodies to HIV type 1 (HIV-1) and HIV type 2 (HIV-2) and HIV-1 p24 antigen was reactive. Plasma HIV-1 RNA was not detected. The CD4+ T-cell count was 39 per microliter (reference range, 348 to 1456). Other laboratory test results are shown in Table 1. A urine sample was obtained for culture. CT of the chest, performed after the administration of intravenous contrast material, revealed a mildly enlarged and multinodular left thyroid gland, as well as scattered pulmonary nodules measuring less than 4 mm in diameter. CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a hypoattenuating hepatic lesion measuring 1.1 cm in the greatest dimension that was consistent with hemangioma, as well as diffuse lytic osseous lesions in the thoracolumbar spine and pelvis.	
Table 1  
Diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 53-year-old woman was transferred to this hospital because of progressive headache, gait instability, and weight loss.
Approximately 2 months before the patient's evaluation at this hospital, vertigo developed and resolved spontaneously. One day before evaluation at this hospital, she sought care at another hospital for recurrent dizziness and difficulty walking. The temperature was 36.4[degrees]C, the pulse 86 beats per minute, the blood pressure 170/105 mm Hg, the respiratory rate 15 breaths per minute, and the oxygen saturation 97% while she was breathing ambient air. The patient was alert and oriented, with slow speech, bilateral end-point horizontal nystagmus, and mild dysmetria on the right side on finger-nose-finger testing. Strength and sensory function were normal. She had difficulty maintaining a stable stance; her gait was narrow-based and described as ""slow and cautious."" The remainder of the examination was normal.
Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, showed an area of ill-defined hypoattenuation that was consistent with vasogenic edema in the right cerebellar hemisphere, as well as regions of white-matter hypoattenuation in both cerebellar hemispheres. Aspirin and atorvastatin were administered.
Dr. R. Gilberto Gonzalez: Magnetic resonance imaging (MRI) of the head (Figure 1), performed before and after the administration of intravenous contrast material, revealed an enhancing intraaxial lesion, measuring 2.0 cm by 1.8 cm by 1.7 cm, in the right inferior cerebellar hemisphere. The lesion had internal signal hypointensity that was indicative of necrosis on T1-weighted imaging, as well as surrounding signal hyperintensity that was suggestive of vasogenic edema on T2-weighted imaging. There was local mass effect with effacement of the overlying cerebellar fissures and the fourth ventricle. There was also an enhancing leptomeningeal lesion, measuring 4 mm in diameter, along the left medial frontal lobe in the left superior frontal gyrus, with possible leptomeningeal extension. The lesion was characterized by internal and surrounding signal hyperintensity on T2-weighted imaging.	
Figure 1 
Dr. Rosenberg: Intravenous dexamethasone, amlodipine, and labetalol were administered. The patient was transferred to this hospital for specialized neurosurgical consultation.
On evaluation at this hospital, review of systems was notable for malaise and lethargy, as well as unintentional weight loss of 15 kg during the past year. The patient also reported an increase in urinary frequency without hematuria, dysuria, or flank pain. She had no fever, chills, sinus pain, dyspnea, cough, abdominal pain, diarrhea, nausea, or vomiting. She had a history of hypertension and hemorrhagic stroke, which had led to a craniotomy on the right side for evacuation of a ""blood clot"" 13 years before the current evaluation, with no reported neurologic deficits.
The patient reported that, during the admission for craniotomy, she was told that she had human immunodeficiency virus (HIV) infection and was treated with an unknown antiretroviral therapy (ART) regimen; she could not recall the medications included in the regimen. In addition, she reported that, several years later, further testing revealed that an error had been made and she did not have HIV infection. She reported that ART medications were discontinued at least 3 years before the current evaluation.
The patient did not have a history of opportunistic infections or cancer. Three years earlier, a Mantoux tuberculin skin test had been negative. One week earlier, a mammogram had been normal. She had never undergone a colonoscopy or a Papanicolaou test.
The patient was born in Ivory Coast, West Africa, and had been living in the United States for more than 20 years. She reported no recent travel. She lived with her children and did not smoke tobacco, drink alcohol, or use illicit drugs. She was divorced and not sexually active; in her lifetime, she had had one male sexual partner. Her ex-husband and one of her children reportedly had tested negative for HIV. Her father had had a myocardial infarction in his 60s; her mother and sisters were healthy. The patient had not been taking any medications at home before this illness and had no known allergies to medications.
On physical examination, the temperature was 36.9[degrees]C, the blood pressure 165/99 mm Hg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 22.5. The patient was comfortable, alert, and oriented. Her speech was clear, with intact naming and repetition. Her pupils were equal and reactive to light, extraocular movements were intact, and visual fields were full in response to confrontation. She had mild right esotropia and no nystagmus. Her face was symmetric, but there was mild deviation of the tongue to the left. Results of other cranial-nerve testing were normal. Finger-nose-finger testing revealed subtle dysmetria that was greater on the right side than on the left side; there was no dysdiadochokinesia or intention tremor. Her stance was approximately shoulder-width. Her balance was impaired, and her gait was unsteady and ataxic. Psychomotor slowing was present, and the Romberg sign was absent. An evaluation of power, bulk, tone, sensation, and deep-tendon reflexes was normal. She had alopecia and oral thrush. The remainder of the examination was normal. The patient was admitted to the hospital for further evaluation and treatment.
Results of tests of renal, liver, and thyroid function were normal, as were blood levels of electrolytes, vitamin B12, and glycated hemoglobin. An HIV screening test for the detection of antibodies to HIV type 1 (HIV-1) and HIV type 2 (HIV-2) and HIV-1 p24 antigen was reactive. Plasma HIV-1 RNA was not detected. The CD4+ T-cell count was 39 per microliter (reference range, 348 to 1456). Other laboratory test results are shown in Table 1. A urine sample was obtained for culture. CT of the chest, performed after the administration of intravenous contrast material, revealed a mildly enlarged and multinodular left thyroid gland, as well as scattered pulmonary nodules measuring less than 4 mm in diameter. CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a hypoattenuating hepatic lesion measuring 1.1 cm in the greatest dimension that was consistent with hemangioma, as well as diffuse lytic osseous lesions in the thoracolumbar spine and pelvis.	
Table 1  
Diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Primary Central Nervous System Lymphoma (PCNSL) associated with HIV infection. \n\nThe patient's symptoms of progressive headache, gait instability, and weight loss, along with the MRI findings of an enhancing intraaxial lesion in the right inferior cerebellar hemisphere, suggest a central nervous system (CNS) neoplasm. The presence of leptomeningeal lesions further supports this. The patient's history of a previous HIV diagnosis, even though she was later told it was an error, combined with the current finding of a reactive HIV screening test and a low CD4+ T-cell count, suggests that she does indeed have HIV infection. In patients with HIV, the most common CNS neoplasm is primary CNS lymphoma (PCNSL). The presence of systemic findings such as weight loss and malaise, as well as the CT findings of pulmonary nodules and lytic bone lesions, suggest systemic involvement, which is common in HIV-associated PCNSL.""
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        ""content"": ""The patient is a 53-year-old woman presenting with progressive headache, gait instability, and weight loss. She also has a history of hypertension and hemorrhagic stroke. The patient's symptoms and history suggest a neurological condition. The differential diagnosis includes brain tumor, multiple sclerosis, and HIV-associated neurocognitive disorder. The patient's CT scan shows an area of hypoattenuation in the right cerebellar hemisphere and regions of white-matter hypoattenuation in both cerebellar hemispheres. This could be indicative of a brain tumor or multiple sclerosis. However, the patient's MRI reveals an enhancing intraaxial lesion in the right inferior cerebellar hemisphere, which is more indicative of a brain tumor. The patient also has a history of HIV infection, which was reportedly a false positive. However, her current HIV screening test is reactive, and her CD4+ T-cell count is low, suggesting that she may indeed have HIV. HIV can cause neurological symptoms, including gait instability and cognitive impairment. Given the patient's imaging findings, history of a reactive HIV test, and low CD4+ T-cell count, the most likely diagnosis is HIV-associated neurocognitive disorder with a brain lesion.\n\nDiagnosis: HIV-associated neurocognitive disorder with a brain lesion.""
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10.1056/NEJMcpc2004977,Case 25-2020: A 47-Year-Old Woman with a Lung Mass,,Pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infe,Pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infe,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 47-year-old woman presented to this hospital early during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), because of cough and shortness of breath.
The patient had been well until 2 months before this evaluation, when intermittent nonproductive cough and wheezing developed. She had no fever, chills, or shortness of breath. Two days before this evaluation, the cough worsened in frequency and severity and new shortness of breath developed. The patient was evaluated by her primary care physician by telephone call. Humidification, fluticasone nasal spray, and fexofenadine were recommended, as was a follow-up telephone call in 2 weeks.
However, the next day, the patient sought evaluation at the emergency department of this hospital because of worsening shortness of breath with ambulation. A review of systems was notable for rhinorrhea, myalgias, and dizziness. She had no fever, chills, sore throat, chest pain, nausea, vomiting, abdominal pain, diarrhea, leg swelling, or weight loss.
The patient had a history of eczema and gestational diabetes. Medications included azelastine nasal spray, fluocinonide cream, folate, and ferrous sulfate; she had not yet begun to use the fluticasone nasal spray and fexofenadine that had been newly recommended by her primary care physician. There were no known drug allergies. The patient was originally from the equatorial region of South America and had moved to the United States 20 years earlier; she had not traveled outside the United States in many years. She lived in an apartment in an urban area of New England with her husband and five children. She did not drink alcohol, smoke tobacco, or use illicit drugs. Her mother had had diabetes and melanoma.
On examination, the temperature was 38.0[degrees]C, the heart rate 100 beats per minute, the blood pressure 124/64 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. She appeared to be well and was breathing comfortably. The lungs were clear on auscultation. The white-cell count was 4430 per microliter (reference range, 4500 to 11,000); the lymphocyte count was 550 per microliter (reference range, 1000 to 4800). Blood levels of electrolytes and results of liver- and renal-function tests were normal. Nucleic acid testing of a nasopharyngeal swab for influenza A and B viruses and respiratory syncytial virus was negative.
Dr. Jo-Anne O. Shepard: Posteroanterior and lateral radiography of the chest revealed a 4-cm rounded mass in the right lower lobe (Figure 1A and 1B). Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, revealed a rounded mass in the right lower lobe with ground-glass attenuation and a rim of higher attenuation at the periphery of the mass, findings that represent the reversed halo sign (Figure 1C). In addition, there were smaller ground-glass nodules at the periphery of the right middle lobe and left upper lobe, with associated right hilar lymphadenopathy (Figure 1C, 1D, and 1E). These findings are most consistent with viral pneumonia, although primary cancer of the lung cannot be ruled out.	
Figure 1 
Dr. Eisen: Intravenous fluids were administered, and the dizziness abated. Because there was an initial concern about the possibility of lung cancer, a telephone oncology consultation was requested. The patient was discharged from the emergency department. Self-quarantine at home and additional outpatient imaging studies were recommended
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 47-year-old woman presented to this hospital early during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), because of cough and shortness of breath.
The patient had been well until 2 months before this evaluation, when intermittent nonproductive cough and wheezing developed. She had no fever, chills, or shortness of breath. Two days before this evaluation, the cough worsened in frequency and severity and new shortness of breath developed. The patient was evaluated by her primary care physician by telephone call. Humidification, fluticasone nasal spray, and fexofenadine were recommended, as was a follow-up telephone call in 2 weeks.
However, the next day, the patient sought evaluation at the emergency department of this hospital because of worsening shortness of breath with ambulation. A review of systems was notable for rhinorrhea, myalgias, and dizziness. She had no fever, chills, sore throat, chest pain, nausea, vomiting, abdominal pain, diarrhea, leg swelling, or weight loss.
The patient had a history of eczema and gestational diabetes. Medications included azelastine nasal spray, fluocinonide cream, folate, and ferrous sulfate; she had not yet begun to use the fluticasone nasal spray and fexofenadine that had been newly recommended by her primary care physician. There were no known drug allergies. The patient was originally from the equatorial region of South America and had moved to the United States 20 years earlier; she had not traveled outside the United States in many years. She lived in an apartment in an urban area of New England with her husband and five children. She did not drink alcohol, smoke tobacco, or use illicit drugs. Her mother had had diabetes and melanoma.
On examination, the temperature was 38.0[degrees]C, the heart rate 100 beats per minute, the blood pressure 124/64 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. She appeared to be well and was breathing comfortably. The lungs were clear on auscultation. The white-cell count was 4430 per microliter (reference range, 4500 to 11,000); the lymphocyte count was 550 per microliter (reference range, 1000 to 4800). Blood levels of electrolytes and results of liver- and renal-function tests were normal. Nucleic acid testing of a nasopharyngeal swab for influenza A and B viruses and respiratory syncytial virus was negative.
Dr. Jo-Anne O. Shepard: Posteroanterior and lateral radiography of the chest revealed a 4-cm rounded mass in the right lower lobe (Figure 1A and 1B). Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, revealed a rounded mass in the right lower lobe with ground-glass attenuation and a rim of higher attenuation at the periphery of the mass, findings that represent the reversed halo sign (Figure 1C). In addition, there were smaller ground-glass nodules at the periphery of the right middle lobe and left upper lobe, with associated right hilar lymphadenopathy (Figure 1C, 1D, and 1E). These findings are most consistent with viral pneumonia, although primary cancer of the lung cannot be ruled out.	
Figure 1 
Dr. Eisen: Intravenous fluids were administered, and the dizziness abated. Because there was an initial concern about the possibility of lung cancer, a telephone oncology consultation was requested. The patient was discharged from the emergency department. Self-quarantine at home and additional outpatient imaging studies were recommended
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
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10.1056/NEJMcpc2004975,"Case 24-2020: A 44-Year-Old Woman with Chest Pain, Dyspnea, and Shock","Days after symptom onset 8 9 9
Hemoglobin (g/dl)   13.4 13.4 9.6
Hematocrit (%)   40.3 39.7 28.2
White-cell count (per μl)   7240 13,270 9330
Differential count (%)
Neutrophils   67.7 76.5
Lymphocytes   23.9 16.2
Monocytes   8.0 6.8
Eosinophils   0.0 0.0
Platelet count (per μl) 
119,000 124,000 85,000
Sodium (mmol/liter)   139 143 148
Potassium (mmol/liter)   3.9 4.9 4.1
Chloride (mmol/liter)   100 103 111
Carbon dioxide (mmol/liter)   22 19 26
Urea nitrogen (mg/dl)   14 25 14
Creatinine (mg/dl)   0.82 1.19 0.73
Glucose (mg/dl)   160 235 139
Lactate (mmol/liter)   5.5 10.1 4.1
Calcium (mg/dl)   8.4 7.8 8.5
Ionized calcium (mmol/liter)   1.04 1.10
Phosphorus (mg/dl)   3.6 2.0 1.9
Alanine aminotransferase (IU/liter)   242 225
Aspartate aminotransferase (IU/liter)   186 178
Albumin (g/dl)   3.7 3.0
Creatine kinase (IU/liter)   292 501
N-terminal pro–B-type natriuretic peptide (pg/ml) 0–450 6381
High-sensitivity troponin T (ng/liter) 0–9 375 1810 1282
d-dimer (ng/ml)   4903 3489
Lactate dehydrogenase (IU/liter) 11 10 297 346
Mixed venous oxygen saturation (%) 65.0–75.0 46.2
Erythrocyte sedimentation rate (mm/hr)  0 2
C-reactive protein (mg/liter)   4.3
Interleukin-6 (pg/ml)  .5 18.0
Arterial blood gases
Fraction of inspired oxygen 0.60 0.40
pH   7.40 7.38
Partial pressure of carbon dioxide (mm Hg)   31 47
Partial pressure of oxygen (mm Hg)   220 229                                           C-reactive protein (mg/liter)   127.1 4
Interleukin-6 (pg/ml)  .5 53.3 4
d-dimer (ng/ml)   8691 13
Ferritin (ng/ml) 1 00 2564 2","SARS-CoV-2 infection complicated by severe acute 
inflammatory cardiomyopathy and cardiogenic 
shock","SARS-CoV-2 infection complicated by severe acute 
inflammatory cardiomyopathy and cardiogenic 
shock","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 44-year-old woman was admitted to this hospital because of shortness of breath and chest pain.
Eight days before admission - and 3 days after her husband had begun to have fatigue, a nonproductive cough, and a fever - the patient started to have chills, a sore throat, a nonproductive cough, and myalgias. After 2 days of progressive symptoms, she contacted her primary care physician. A telemedicine visit was arranged as part of a local public health strategy to reduce the spread of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during the pandemic. The patient reported that she had rib soreness with coughing, as well as a temperature of 35.3[degrees]C. Infection with SARS-CoV-2 was suspected. Rest, isolation measures to reduce viral transmission, and increased oral intake of fluid were recommended, along with acetaminophen and dextromethorphan-guaifenesin as needed. Three days later, she had diarrhea and back pain, but the coughing had become less frequent. During a follow-up telemedicine visit, the primary care physician recommended that the patient take acetaminophen as needed for back pain and counseled her to seek in-person medical evaluation if symptoms worsened.
Three days later, the patient started to have chest pain that was different from the rib soreness with coughing; the chest pain was present at rest and was accompanied by new dyspnea. She called emergency medical services. On the initial evaluation, the heart rate was 116 beats per minute, the systolic blood pressure 110 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. The patient was brought by ambulance to the emergency department of this hospital.
On arrival, the patient reported feeling weak, light-headed, and feverish, with chills. She reported that the chest discomfort felt like pressure, was primarily located in the anterior chest, and was mild in intensity but worsened with deep inspiration or coughing. She also reported nausea and a few episodes of nonbloody diarrhea. She had received an influenza vaccine 6 months earlier.
The patient's medical history was notable for gastroesophageal reflux disease with histologic evidence of intestinal metaplasia of the esophagus, chronic abdominal bloating and constipation, mild obstructive sleep apnea, subclinical hyperthyroidism, uterine cysts, and depression. Medications included trazodone and acetaminophen as needed. There were no known drug allergies.
The patient was born in Central America and had immigrated to the United States approximately 20 years earlier. She lived in New England with her husband and teenage children. She worked as a custodian but had no known exposure to dust, allergens, or solvents. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had had hypertension and a myocardial infarction; her father had died of genitourinary cancer, and multiple paternal relatives had a history of cancer.
On examination, the temperature was 36.4[degrees]C, the heart rate 103 beats per minute, the blood pressure 79/51 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 23.7. The patient appeared pale and slightly diaphoretic. She was able to speak in full sentences but appeared lethargic. The lungs were clear on auscultation. The heart was tachycardic, with normal first and second heart sounds (S1 and S2) and no gallops (S3 or S4). There was mild, diffuse abdominal tenderness on palpation. The legs were cool to the touch. The remainder of the examination was normal. Lactated Ringer's solution was administered intravenously.
Dr. Judy Hung: Point-of-care cardiac ultrasonography revealed severely depressed left ventricular function. The left ventricular wall thickness was normal; the left ventricular cavity was mildly dilated (Figure 1A; also see Video 1, available with the full text of this article at
NEJM.org
). A trace pericardial effusion was visible.	
Figure 1 
Dr. Zlotoff: On blood testing, human chorionic gonadotropin was undetectable. Blood levels of magnesium, bilirubin, alkaline phosphatase, and free thyroxine were normal, as were the prothrombin time, international normalized ratio, and partial-thromboplastin time; other test results are shown in Table 1. A nasopharyngeal swab was obtained for testing, and blood was obtained for culture. Intravenous vancomycin and cefepime were administered.	
Table 1
Electrocardiography (ECG) showed sinus rhythm at 96 beats per minute, submillimeter ST-segment elevation in leads I and aVL, and low QRS voltage (Figure 1B). Results of chest radiography were normal (Figure 1C).
One hour after the administration of intravenous fluids and antibiotic agents, hypotension persisted and treatment with intravenous norepinephrine was initiated. The patient had a brief episode of unresponsiveness in the context of worsened hypotension, and intravenous dobutamine was added. Repeat bedside cardiac ultrasonography revealed severe left ventricular dysfunction, a small anterior pericardial effusion, and a dilated inferior vena cava without respirophasic variation; the left ventricular wall thickness was normal.
Dr. Andrey Rupasov: Computed tomographic (CT) angiography of the chest, performed after the administration of intravenous contrast material, revealed no evidence of pulmonary embolism. Images of the heart and great vessels showed excellent opacification of the right side of the heart and pulmonary arteries but poor opacification of the left side of the heart and aorta due to prolongation of the pulmonary circulation time, which is suggestive of cardiac dysfunction (Figure 1D). Radiographically significant coronary-artery calcification was absent. Images of the lungs showed a few scattered, predominantly peripheral ground-glass opacities in the lingula, the right middle lobe, and both lower lobes (Figure 1E), as well as a trace pleural effusion. Although the pulmonary findings are nonspecific, they are suggestive of inflammation or infection that, in this clinical context, is likely to be due to SARS-CoV-2. Because the patient had abdominal tenderness and hypotension, a CT scan of the abdomen and pelvis was also obtained; the images showed a small amount of ascites and periportal edema, findings that are indicative of elevated central venous pressure.
Dr. Zlotoff: Three hours after the initial presentation, the patient was admitted to the cardiac intensive care unit (ICU). She was lethargic and reported nausea. The temperature was 36.4[degrees]C, the heart rate 121 beats per minute, the blood pressure 99/79 mm Hg while she was receiving norepinephrine and dobutamine, the respiratory rate 24 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The arms and legs were cool.
Specialists in heart failure, critical care, and cardiac surgery were consulted. During the next 4 hours, catheters were placed in the radial artery and in the pulmonary artery through the right internal jugular vein. Arterial blood gas measurements, obtained while the patient was breathing ambient air, were notable for a pH of 7.45, a partial pressure of carbon dioxide of 20 mm Hg, and a partial pressure of oxygen of 103 mm Hg. The central venous pressure was 21 mm Hg, the pulmonary arterial pressure 37/19 mm Hg, the pulmonary capillary wedge pressure 25 mm Hg, and the thermodilution cardiac output 2.2 liters per minute. The dose of dobutamine was increased. Testing of the nasopharyngeal swab was negative for influenza A and B virus and respiratory syncytial virus DNA but was positive for SARS-CoV-2 RNA.
During the next 3 hours, the patient remained lethargic, with light-headedness, nausea, and one episode of nonbloody emesis. The temperature increased to 37.9[degrees]C, the heart rate to 140 beats per minute, and the respiratory rate to 31 breaths per minute; the blood pressure was labile, with intermittent episodes of a systolic blood pressure lower than 70 mm Hg despite treatment with norepinephrine and dobutamine. The trachea was intubated and mechanical ventilation was initiated to reduce cardiopulmonary metabolic demands. Intravenous vasopressin and milrinone were added. The heart rate remained higher than 140 beats per minute, the systolic blood pressure remained lower than 70 mm Hg, and the thermodilution cardiac output was 1.7 liters per minute. Oliguria developed. Additional laboratory studies were obtained (Table 1). Urgent management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 44-year-old woman was admitted to this hospital because of shortness of breath and chest pain.
Eight days before admission - and 3 days after her husband had begun to have fatigue, a nonproductive cough, and a fever - the patient started to have chills, a sore throat, a nonproductive cough, and myalgias. After 2 days of progressive symptoms, she contacted her primary care physician. A telemedicine visit was arranged as part of a local public health strategy to reduce the spread of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during the pandemic. The patient reported that she had rib soreness with coughing, as well as a temperature of 35.3[degrees]C. Infection with SARS-CoV-2 was suspected. Rest, isolation measures to reduce viral transmission, and increased oral intake of fluid were recommended, along with acetaminophen and dextromethorphan-guaifenesin as needed. Three days later, she had diarrhea and back pain, but the coughing had become less frequent. During a follow-up telemedicine visit, the primary care physician recommended that the patient take acetaminophen as needed for back pain and counseled her to seek in-person medical evaluation if symptoms worsened.
Three days later, the patient started to have chest pain that was different from the rib soreness with coughing; the chest pain was present at rest and was accompanied by new dyspnea. She called emergency medical services. On the initial evaluation, the heart rate was 116 beats per minute, the systolic blood pressure 110 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. The patient was brought by ambulance to the emergency department of this hospital.
On arrival, the patient reported feeling weak, light-headed, and feverish, with chills. She reported that the chest discomfort felt like pressure, was primarily located in the anterior chest, and was mild in intensity but worsened with deep inspiration or coughing. She also reported nausea and a few episodes of nonbloody diarrhea. She had received an influenza vaccine 6 months earlier.
The patient's medical history was notable for gastroesophageal reflux disease with histologic evidence of intestinal metaplasia of the esophagus, chronic abdominal bloating and constipation, mild obstructive sleep apnea, subclinical hyperthyroidism, uterine cysts, and depression. Medications included trazodone and acetaminophen as needed. There were no known drug allergies.
The patient was born in Central America and had immigrated to the United States approximately 20 years earlier. She lived in New England with her husband and teenage children. She worked as a custodian but had no known exposure to dust, allergens, or solvents. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had had hypertension and a myocardial infarction; her father had died of genitourinary cancer, and multiple paternal relatives had a history of cancer.
On examination, the temperature was 36.4[degrees]C, the heart rate 103 beats per minute, the blood pressure 79/51 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 23.7. The patient appeared pale and slightly diaphoretic. She was able to speak in full sentences but appeared lethargic. The lungs were clear on auscultation. The heart was tachycardic, with normal first and second heart sounds (S1 and S2) and no gallops (S3 or S4). There was mild, diffuse abdominal tenderness on palpation. The legs were cool to the touch. The remainder of the examination was normal. Lactated Ringer's solution was administered intravenously.
Dr. Judy Hung: Point-of-care cardiac ultrasonography revealed severely depressed left ventricular function. The left ventricular wall thickness was normal; the left ventricular cavity was mildly dilated (Figure 1A; also see Video 1, available with the full text of this article at
NEJM.org
). A trace pericardial effusion was visible.	
Figure 1 
Dr. Zlotoff: On blood testing, human chorionic gonadotropin was undetectable. Blood levels of magnesium, bilirubin, alkaline phosphatase, and free thyroxine were normal, as were the prothrombin time, international normalized ratio, and partial-thromboplastin time; other test results are shown in Table 1. A nasopharyngeal swab was obtained for testing, and blood was obtained for culture. Intravenous vancomycin and cefepime were administered.	
Table 1
Electrocardiography (ECG) showed sinus rhythm at 96 beats per minute, submillimeter ST-segment elevation in leads I and aVL, and low QRS voltage (Figure 1B). Results of chest radiography were normal (Figure 1C).
One hour after the administration of intravenous fluids and antibiotic agents, hypotension persisted and treatment with intravenous norepinephrine was initiated. The patient had a brief episode of unresponsiveness in the context of worsened hypotension, and intravenous dobutamine was added. Repeat bedside cardiac ultrasonography revealed severe left ventricular dysfunction, a small anterior pericardial effusion, and a dilated inferior vena cava without respirophasic variation; the left ventricular wall thickness was normal.
Dr. Andrey Rupasov: Computed tomographic (CT) angiography of the chest, performed after the administration of intravenous contrast material, revealed no evidence of pulmonary embolism. Images of the heart and great vessels showed excellent opacification of the right side of the heart and pulmonary arteries but poor opacification of the left side of the heart and aorta due to prolongation of the pulmonary circulation time, which is suggestive of cardiac dysfunction (Figure 1D). Radiographically significant coronary-artery calcification was absent. Images of the lungs showed a few scattered, predominantly peripheral ground-glass opacities in the lingula, the right middle lobe, and both lower lobes (Figure 1E), as well as a trace pleural effusion. Although the pulmonary findings are nonspecific, they are suggestive of inflammation or infection that, in this clinical context, is likely to be due to SARS-CoV-2. Because the patient had abdominal tenderness and hypotension, a CT scan of the abdomen and pelvis was also obtained; the images showed a small amount of ascites and periportal edema, findings that are indicative of elevated central venous pressure.
Dr. Zlotoff: Three hours after the initial presentation, the patient was admitted to the cardiac intensive care unit (ICU). She was lethargic and reported nausea. The temperature was 36.4[degrees]C, the heart rate 121 beats per minute, the blood pressure 99/79 mm Hg while she was receiving norepinephrine and dobutamine, the respiratory rate 24 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The arms and legs were cool.
Specialists in heart failure, critical care, and cardiac surgery were consulted. During the next 4 hours, catheters were placed in the radial artery and in the pulmonary artery through the right internal jugular vein. Arterial blood gas measurements, obtained while the patient was breathing ambient air, were notable for a pH of 7.45, a partial pressure of carbon dioxide of 20 mm Hg, and a partial pressure of oxygen of 103 mm Hg. The central venous pressure was 21 mm Hg, the pulmonary arterial pressure 37/19 mm Hg, the pulmonary capillary wedge pressure 25 mm Hg, and the thermodilution cardiac output 2.2 liters per minute. The dose of dobutamine was increased. Testing of the nasopharyngeal swab was negative for influenza A and B virus and respiratory syncytial virus DNA but was positive for SARS-CoV-2 RNA.
During the next 3 hours, the patient remained lethargic, with light-headedness, nausea, and one episode of nonbloody emesis. The temperature increased to 37.9[degrees]C, the heart rate to 140 beats per minute, and the respiratory rate to 31 breaths per minute; the blood pressure was labile, with intermittent episodes of a systolic blood pressure lower than 70 mm Hg despite treatment with norepinephrine and dobutamine. The trachea was intubated and mechanical ventilation was initiated to reduce cardiopulmonary metabolic demands. Intravenous vasopressin and milrinone were added. The heart rate remained higher than 140 beats per minute, the systolic blood pressure remained lower than 70 mm Hg, and the thermodilution cardiac output was 1.7 liters per minute. Oliguria developed. Additional laboratory studies were obtained (Table 1). Urgent management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 44-year-old woman presenting with shortness of breath, chest pain, and a history of recent flu-like symptoms. Her husband had similar symptoms, and she was suspected to have SARS-CoV-2 infection. Her symptoms progressed to include diarrhea, back pain, and chest pain at rest with new dyspnea. On examination, she was found to have severely depressed left ventricular function, suggestive of heart failure. Her blood pressure was low, and she had tachycardia. She also tested positive for SARS-CoV-2. The differential diagnosis for this patient includes acute myocarditis, acute coronary syndrome, and heart failure. Acute coronary syndrome is less likely given the absence of significant coronary artery calcification on CT angiography. Acute myocarditis could be a possibility, especially given her recent viral illness. However, the patient's severely depressed left ventricular function, low blood pressure, and tachycardia are indicative of heart failure. Given the patient's recent SARS-CoV-2 infection, it is likely that this is a case of COVID-19 related myocarditis leading to acute heart failure.\n\nDiagnosis: Acute heart failure secondary to COVID-19 related myocarditis.""
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}",Acute heart failure secondary to COVID-19 related myocarditis,Y
10.1056/NEJMcpc2004974,Case 23-2020: A 76-Year-Old Woman Who Died from Covid-19,"Hemoglobin (g/dl)   13.9
Hematocrit (%)   43.2
White-cell count (per μl)   7690
Differential count (per μl)
Neutrophils   6150
Lymphocytes   1270
Monocytes   200
Basophils  00 70
Platelet count (per μl)   149,000
Sodium (mmol/liter)   136
Potassium (mmol/liter)   4.2
Chloride (mmol/liter)   94
Carbon dioxide (mmol/liter)   22
Anion gap (mmol/liter)   20
Urea nitrogen (mg/dl)   13
Creatinine (mg/dl)   0.65
Glucose (mg/dl)   366
Alanine aminotransferase (U/liter)   27
Aspartate aminotransferase (U/liter)   35
Alkaline phosphatase (U/liter)   54
Creatine kinase (U/liter)   363
Lactate dehydrogenase (U/liter) 11 10 289
Ferritin (μg/liter) 1 00 675
d-dimer (ng/ml)   3592",Diffuse alveolar damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection,Acute respiratory distress syndrome due to coronavirus disease 2019 (Covid-19).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old woman was admitted to this hospital because of confusion and hypoxemia during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient had been well until 6 days before this admission, when nasal congestion developed, with no fever or cough. One day before this admission, she called her primary care physician, who recommended fluticasone nasal spray and nasal rinses and asked her to follow up by telephone in 2 days. However, the next day, the patient's son visited the patient and found her to be confused and incontinent of urine and stool. Emergency medical services were called, and when they arrived at the patient's home, the oxygen saturation was 87% while she was breathing ambient air. The patient was transported by ambulance to this hospital.
In the emergency department, the patient reported chills but no fever, cough, shortness of breath, sore throat, chest pain, or dysuria. Additional information was obtained from the patient's daughter and son by telephone. There was a history of asthma, diabetes, hypertension, hyperlipidemia, osteoporosis, and psoriasis. Medications included atorvastatin, aspirin, hydrochlorothiazide, losartan, insulin, metformin, glipizide, citalopram, acetaminophen, cholecalciferol, folate, fluticasone nasal spray, and topical betamethasone and fluocinonide. Lisinopril had caused a cough; penicillin and sulfa drugs had caused hives. The patient was widowed and lived in an assisted-living facility where multiple residents had recently received a diagnosis of Covid-19. She did not smoke tobacco or use electronic cigarettes, alcohol, or illicit drugs. Her family history included diabetes and cancer in both her father and her brother; her daughter and son were well.
The temperature was 38.8[degrees]C, the heart rate 94 beats per minute, the blood pressure 176/55 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 94% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. On examination, the patient appeared ill and was lethargic. She was alert and oriented but unable to recall events from earlier in the day. The lungs were clear on auscultation. The white-cell count was 7690 per microliter (reference range, 4500 to 11,000); the blood D-dimer level was 3592 ng per milliliter (reference range,  ). Urinalysis results were normal. Nucleic acid testing of a nasopharyngeal swab was negative for influenza A and B viruses and respiratory syncytial virus but was positive for SARS-CoV-2. Other test results are shown in Table 1.	
Table 1 
Dr. John Conklin: On radiography of the chest (Figure 1A), patchy airspace opacities were present in the left upper lobe and surrounding the hilum. On computed tomographic (CT) pulmonary angiography of the chest (Figure 1B, 1C, and 1D), performed after the administration of intravenous contrast material, multifocal consolidative and ground-glass opacities, including some with rounded morphologic features, were present in both lungs. These findings have been commonly reported with Covid-19 pneumonia, although other processes, such as influenza pneumonia and organizing pneumonia, may have a similar appearance on imaging.1 There was no evidence of pulmonary embolism.	
Figure 1 
Dr. Tran: Acetaminophen and empirical ceftriaxone, azithromycin, and hydroxychloroquine were administered. Because the patient had acute respiratory failure and Covid-19, goals of care were discussed with her adult children by telephone; the patient was unable to participate meaningfully in the discussion because of confusion. She had recently expressed to her primary care doctor that she would ""not want to be on a breathing machine if something were irreversible."" A status of ""do not resuscitate and do not intubate"" was assigned.
During the next day, intermittent episodes of fever occurred, with temperatures as high as 40.3[degrees]C, and delirium and hypoxemia worsened. On the third hospital day, new atrial fibrillation with a rapid ventricular response developed, and metoprolol and furosemide were administered.
On the fourth hospital day, the respiratory rate was 36 breaths per minute and the oxygen saturation was 90% while the patient was receiving supplemental oxygen through a nonrebreather mask at a rate of 15 liters per minute. She appeared to be in distress, with increased work of breathing. Goals of care were again discussed with the patient's family, and a status of ""comfort measures only"" was assigned. The patient died 36 hours later. After discussion with the family, an autopsy was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 76-year-old woman was admitted to this hospital because of confusion and hypoxemia during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient had been well until 6 days before this admission, when nasal congestion developed, with no fever or cough. One day before this admission, she called her primary care physician, who recommended fluticasone nasal spray and nasal rinses and asked her to follow up by telephone in 2 days. However, the next day, the patient's son visited the patient and found her to be confused and incontinent of urine and stool. Emergency medical services were called, and when they arrived at the patient's home, the oxygen saturation was 87% while she was breathing ambient air. The patient was transported by ambulance to this hospital.
In the emergency department, the patient reported chills but no fever, cough, shortness of breath, sore throat, chest pain, or dysuria. Additional information was obtained from the patient's daughter and son by telephone. There was a history of asthma, diabetes, hypertension, hyperlipidemia, osteoporosis, and psoriasis. Medications included atorvastatin, aspirin, hydrochlorothiazide, losartan, insulin, metformin, glipizide, citalopram, acetaminophen, cholecalciferol, folate, fluticasone nasal spray, and topical betamethasone and fluocinonide. Lisinopril had caused a cough; penicillin and sulfa drugs had caused hives. The patient was widowed and lived in an assisted-living facility where multiple residents had recently received a diagnosis of Covid-19. She did not smoke tobacco or use electronic cigarettes, alcohol, or illicit drugs. Her family history included diabetes and cancer in both her father and her brother; her daughter and son were well.
The temperature was 38.8[degrees]C, the heart rate 94 beats per minute, the blood pressure 176/55 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 94% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. On examination, the patient appeared ill and was lethargic. She was alert and oriented but unable to recall events from earlier in the day. The lungs were clear on auscultation. The white-cell count was 7690 per microliter (reference range, 4500 to 11,000); the blood D-dimer level was 3592 ng per milliliter (reference range,  ). Urinalysis results were normal. Nucleic acid testing of a nasopharyngeal swab was negative for influenza A and B viruses and respiratory syncytial virus but was positive for SARS-CoV-2. Other test results are shown in Table 1.	
Table 1 
Dr. John Conklin: On radiography of the chest (Figure 1A), patchy airspace opacities were present in the left upper lobe and surrounding the hilum. On computed tomographic (CT) pulmonary angiography of the chest (Figure 1B, 1C, and 1D), performed after the administration of intravenous contrast material, multifocal consolidative and ground-glass opacities, including some with rounded morphologic features, were present in both lungs. These findings have been commonly reported with Covid-19 pneumonia, although other processes, such as influenza pneumonia and organizing pneumonia, may have a similar appearance on imaging.1 There was no evidence of pulmonary embolism.	
Figure 1 
Dr. Tran: Acetaminophen and empirical ceftriaxone, azithromycin, and hydroxychloroquine were administered. Because the patient had acute respiratory failure and Covid-19, goals of care were discussed with her adult children by telephone; the patient was unable to participate meaningfully in the discussion because of confusion. She had recently expressed to her primary care doctor that she would ""not want to be on a breathing machine if something were irreversible."" A status of ""do not resuscitate and do not intubate"" was assigned.
During the next day, intermittent episodes of fever occurred, with temperatures as high as 40.3[degrees]C, and delirium and hypoxemia worsened. On the third hospital day, new atrial fibrillation with a rapid ventricular response developed, and metoprolol and furosemide were administered.
On the fourth hospital day, the respiratory rate was 36 breaths per minute and the oxygen saturation was 90% while the patient was receiving supplemental oxygen through a nonrebreather mask at a rate of 15 liters per minute. She appeared to be in distress, with increased work of breathing. Goals of care were again discussed with the patient's family, and a status of ""comfort measures only"" was assigned. The patient died 36 hours later. After discussion with the family, an autopsy was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 76-year-old woman who presented with confusion and hypoxemia. She had a history of asthma, diabetes, hypertension, hyperlipidemia, osteoporosis, and psoriasis. She lived in an assisted-living facility where multiple residents had recently been diagnosed with Covid-19. Her symptoms started with nasal congestion, and she was found to be confused and incontinent of urine and stool. In the hospital, she had a fever and her oxygen saturation was low. A nasopharyngeal swab was positive for SARS-CoV-2. Her condition worsened over the next few days, with intermittent episodes of fever, worsening delirium and hypoxemia, and new atrial fibrillation. Despite treatment, her respiratory distress increased and she died. Given her symptoms, the positive test for SARS-CoV-2, and the progression of her illness, the diagnosis is Covid-19.""
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        ""content"": ""The patient is a 76-year-old woman who presented with confusion and hypoxemia. She had a history of asthma, diabetes, hypertension, hyperlipidemia, osteoporosis, and psoriasis. She lived in an assisted-living facility where multiple residents had recently been diagnosed with Covid-19. Her symptoms started with nasal congestion, and she later developed chills. She was found to be confused and incontinent of urine and stool. In the hospital, her oxygen saturation was low, and she was lethargic. She tested positive for SARS-CoV-2. Her condition worsened over the next few days, with intermittent episodes of fever, worsening delirium and hypoxemia, and new atrial fibrillation. Her respiratory rate increased, and her oxygen saturation decreased despite receiving supplemental oxygen. She died 36 hours later. Given her symptoms, the progression of her illness, and her positive test for SARS-CoV-2, the diagnosis is Covid-19.""
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        ""content"": ""The patient is a 76-year-old woman with a history of asthma, diabetes, hypertension, hyperlipidemia, osteoporosis, and psoriasis. She was admitted to the hospital due to confusion and hypoxemia. She had nasal congestion six days prior to admission and was found to be confused and incontinent of urine and stool by her son. She reported chills but no fever, cough, shortness of breath, sore throat, chest pain, or dysuria. She lived in an assisted-living facility where multiple residents had recently been diagnosed with Covid-19. Her temperature was elevated, and she appeared ill and lethargic. She was alert and oriented but unable to recall events from earlier in the day. Her lungs were clear on auscultation. The white-cell count was within normal range, but the blood D-dimer level was elevated. Urinalysis results were normal. Nucleic acid testing of a nasopharyngeal swab was negative for influenza A and B viruses and respiratory syncytial virus but was positive for SARS-CoV-2. Chest radiography showed patchy airspace opacities in the left upper lobe and surrounding the hilum. CT pulmonary angiography of the chest showed multifocal consolidative and ground-glass opacities in both lungs, which are commonly reported with Covid-19 pneumonia. There was no evidence of pulmonary embolism. The patient's condition worsened over the next few days, and she died on the fourth hospital day.\n\nThe differential diagnosis for this patient includes Covid-19, influenza, and other respiratory infections. However, the patient's symptoms, the recent outbreak of Covid-19 in her assisted-living facility, and the positive test for SARS-CoV-2 strongly suggest that she has Covid-19. The ground-glass opacities seen on the CT scan are also characteristic of Covid-19. The patient's confusion could be due to hypoxemia caused by the disease. The elevated D-dimer level could indicate a coagulation abnormality, which has been associated with severe Covid-19. The patient's other comorbidities, such as diabetes and hypertension, could have made her more susceptible to severe disease.\n\nDiagnosis: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, or Covid-19.""
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10.1056/NEJMcpc2002422,Case 22-2020: A 62-Year-Old Woman with Early Breast Cancer during the Covid-19 Pandemic,,"Invasive ductal carcinoma of the left breast, clinical prognostic stage IB (T2N0), estrogen receptor–positive, progesterone receptor–positive, human epidermal growth factor receptor 2–negative, grade 2, with an intermediate recurrence score on the 21-gene assay","Invasive ductal carcinoma of the left breast, clinical prognostic stage IB (T2N0), estrogen receptor–positive, progesterone receptor–positive, human epidermal growth factor receptor 2–negative, grade 2, with an intermediate recurrence score on the 21-gene assay","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 62-year-old woman was evaluated at this hospital after she had identified a mass in her left breast, confirmed by her physician on physical examination, during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient, who was of Ashkenazi Jewish ancestry, had no known family history of breast or ovarian cancer. Medical history included asthma and a fibroadenoma in the left breast, for which she had undergone excisional biopsy 30 years earlier. Menarche had occurred at 12 years of age and menopause at 54 years of age; she had not received hormone-replacement therapy.
Physical examination revealed a mass, measuring 3 cm in greatest dimension, in the left breast. No other masses or axillary lymph nodes were palpable. The patient underwent imaging studies in accordance with the American College of Radiology guidelines.1 Both breasts were imaged, since the patient's last mammogram had been obtained 7 years earlier.
Dr. Gary X. Wang: Mammography revealed an irregular mass with spiculated margins underlying the skin marker in the left breast, with imaging characteristics highly suggestive of cancer (Figure 1A, 1B, and 1C).2 Subsequent ultrasound examination revealed a solid, irregular mass in the left breast that measured 3.1 cm by 1.5 cm by 1.2 cm (Figure 1D) and normal left axillary lymph nodes. Tissue sampling with core-needle biopsy under ultrasonographic guidance was performed (Figure 1E)
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 62-year-old woman was evaluated at this hospital after she had identified a mass in her left breast, confirmed by her physician on physical examination, during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient, who was of Ashkenazi Jewish ancestry, had no known family history of breast or ovarian cancer. Medical history included asthma and a fibroadenoma in the left breast, for which she had undergone excisional biopsy 30 years earlier. Menarche had occurred at 12 years of age and menopause at 54 years of age; she had not received hormone-replacement therapy.
Physical examination revealed a mass, measuring 3 cm in greatest dimension, in the left breast. No other masses or axillary lymph nodes were palpable. The patient underwent imaging studies in accordance with the American College of Radiology guidelines.1 Both breasts were imaged, since the patient's last mammogram had been obtained 7 years earlier.
Dr. Gary X. Wang: Mammography revealed an irregular mass with spiculated margins underlying the skin marker in the left breast, with imaging characteristics highly suggestive of cancer (Figure 1A, 1B, and 1C).2 Subsequent ultrasound examination revealed a solid, irregular mass in the left breast that measured 3.1 cm by 1.5 cm by 1.2 cm (Figure 1D) and normal left axillary lymph nodes. Tissue sampling with core-needle biopsy under ultrasonographic guidance was performed (Figure 1E)
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Breast Cancer\n\nThe patient presented with a mass in her left breast, which was confirmed by her physician. Mammography revealed an irregular mass with spiculated margins, which is highly suggestive of cancer. Subsequent ultrasound examination revealed a solid, irregular mass in the left breast. Tissue sampling with core-needle biopsy under ultrasonographic guidance was performed, which is a common procedure to confirm the diagnosis of breast cancer.""
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        ""content"": ""Breast Cancer. The patient is a 62-year-old woman who found a mass in her left breast. The mass was confirmed by her physician on physical examination. Mammography revealed an irregular mass with spiculated margins in the left breast, which is highly suggestive of cancer. Subsequent ultrasound examination revealed a solid, irregular mass in the left breast. Tissue sampling with core-needle biopsy under ultrasonographic guidance was performed, which is a common procedure to confirm the diagnosis of breast cancer.""
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        ""content"": ""The patient is a 62-year-old woman who presents with a mass in her left breast. She has a history of fibroadenoma in the same breast, but that was 30 years ago. The differential diagnosis for this patient includes benign breast conditions such as fibroadenoma or cysts, and malignant conditions such as breast cancer. Given her age, postmenopausal status, and the characteristics of the mass on imaging (irregular with spiculated margins), malignancy is more likely. The mass was also solid on ultrasound, which is more suggestive of a malignant process. The absence of axillary lymph nodes could suggest that if this is a malignancy, it may not have metastasized yet. However, the definitive diagnosis would depend on the results of the biopsy.\n\nDiagnosis: \nBreast cancer is the most likely diagnosis, pending biopsy results.""
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10.1056/NEJMcpc2002421,Case 21-2020: A 66-Year-Old Homeless Man with Covid-19,,Severe acute respiratory syndrome coronavirus 2  (SARS-CoV-2) infection in a homeless patient.,Severe acute respiratory syndrome coronavirus 2  (SARS-CoV-2) infection in a homeless patient.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 66-year-old homeless man who had sought refuge at a local men's congregate shelter for the past several years was evaluated for cough and rhinorrhea during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Nine days before the current evaluation, the patient presented to a Boston Health Care for the Homeless Program (BHCHP) clinic at a local homeless shelter for evaluation of dry cough and rhinorrhea that had developed earlier that morning. He reported no fever, chills, sore throat, anosmia, myalgias, headache, chest pain, shortness of breath, hemoptysis, diarrhea, nausea, vomiting, or fatigue. He had had no known sick contacts or exposure to anyone with a diagnosis of Covid-19. He had received a seasonal influenza vaccination. A review of systems was notable for cough, rhinorrhea, insomnia, and chronic musculoskeletal pain.
The patient's medical history was notable for ischemic stroke 9 years earlier with residual mild ambulatory deficits, type 2 diabetes mellitus, hypertension, hyperlipidemia, abdominal aortic aneurysm, hyperthyroidism, and obesity. Medications included aspirin, atorvastatin, insulin glargine, metformin, empagliflozin, dulaglutide, losartan, chlorthalidone, amlodipine, metoprolol, and methimazole, along with trazodone, gabapentin, and acetaminophen as needed. All the patient's medications were stored at the BHCHP clinic at the shelter, which provided access to a refrigerator dedicated for proper storage of temperature-sensitive medications. He had no known adverse reactions to medications.
The patient had immigrated to the United States from the Caribbean more than 30 years earlier. He had a history of alcohol use disorder but had abstained from drinking for several years. He had smoked one pack of cigarettes daily for 30 years but had quit 4 years earlier. There was no history of illicit substance use. His family medical history was unknown.
On examination, the temperature was 36.8[degrees]C, the blood pressure 127/57 mm Hg, the heart rate 71 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 31.6. The patient appeared to be well and in no distress. He was alert and oriented. The oropharynx was clear and moist. The lungs were clear on auscultation. The remainder of the examination was normal. Point-of-care blood testing revealed an elevated postprandial glucose level of 260 mg per deciliter (14.4 mmol per liter; normal range, <180 mg per deciliter [10 mmol per liter]). No additional laboratory testing or imaging was performed. Rest and oral hydration were recommended, along with ibuprofen and over-the-counter cough suppressants as needed for symptom relief. The patient returned to the congregate shelter.
Seven days later, in response to a newly recognized cluster of Covid-19 cases at the shelter and with the support of the state public health authority, the BHCHP launched a campaign for universal testing of all guests at the shelter.1 A nasopharyngeal swab was obtained from the patient at a testing tent adjacent to the shelter and was sent to the Massachusetts State Public Health Laboratory to be tested for SARS-CoV-2 RNA. At the time that the specimen was obtained, the patient reported no new symptoms.
Two days later, the test returned positive for SARS-CoV-2 RNA. The shelter staff were notified of the result, and an alert was placed on the shelter intake database. When the patient presented to the shelter that evening, management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 66-year-old homeless man who had sought refuge at a local men's congregate shelter for the past several years was evaluated for cough and rhinorrhea during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Nine days before the current evaluation, the patient presented to a Boston Health Care for the Homeless Program (BHCHP) clinic at a local homeless shelter for evaluation of dry cough and rhinorrhea that had developed earlier that morning. He reported no fever, chills, sore throat, anosmia, myalgias, headache, chest pain, shortness of breath, hemoptysis, diarrhea, nausea, vomiting, or fatigue. He had had no known sick contacts or exposure to anyone with a diagnosis of Covid-19. He had received a seasonal influenza vaccination. A review of systems was notable for cough, rhinorrhea, insomnia, and chronic musculoskeletal pain.
The patient's medical history was notable for ischemic stroke 9 years earlier with residual mild ambulatory deficits, type 2 diabetes mellitus, hypertension, hyperlipidemia, abdominal aortic aneurysm, hyperthyroidism, and obesity. Medications included aspirin, atorvastatin, insulin glargine, metformin, empagliflozin, dulaglutide, losartan, chlorthalidone, amlodipine, metoprolol, and methimazole, along with trazodone, gabapentin, and acetaminophen as needed. All the patient's medications were stored at the BHCHP clinic at the shelter, which provided access to a refrigerator dedicated for proper storage of temperature-sensitive medications. He had no known adverse reactions to medications.
The patient had immigrated to the United States from the Caribbean more than 30 years earlier. He had a history of alcohol use disorder but had abstained from drinking for several years. He had smoked one pack of cigarettes daily for 30 years but had quit 4 years earlier. There was no history of illicit substance use. His family medical history was unknown.
On examination, the temperature was 36.8[degrees]C, the blood pressure 127/57 mm Hg, the heart rate 71 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 31.6. The patient appeared to be well and in no distress. He was alert and oriented. The oropharynx was clear and moist. The lungs were clear on auscultation. The remainder of the examination was normal. Point-of-care blood testing revealed an elevated postprandial glucose level of 260 mg per deciliter (14.4 mmol per liter; normal range, <180 mg per deciliter [10 mmol per liter]). No additional laboratory testing or imaging was performed. Rest and oral hydration were recommended, along with ibuprofen and over-the-counter cough suppressants as needed for symptom relief. The patient returned to the congregate shelter.
Seven days later, in response to a newly recognized cluster of Covid-19 cases at the shelter and with the support of the state public health authority, the BHCHP launched a campaign for universal testing of all guests at the shelter.1 A nasopharyngeal swab was obtained from the patient at a testing tent adjacent to the shelter and was sent to the Massachusetts State Public Health Laboratory to be tested for SARS-CoV-2 RNA. At the time that the specimen was obtained, the patient reported no new symptoms.
Two days later, the test returned positive for SARS-CoV-2 RNA. The shelter staff were notified of the result, and an alert was placed on the shelter intake database. When the patient presented to the shelter that evening, management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient initially presented with symptoms of dry cough and rhinorrhea, which are common symptoms of a respiratory infection. He had no known exposure to anyone with a diagnosis of Covid-19. However, given the ongoing Covid-19 pandemic and the fact that he was living in a congregate shelter, he was at a higher risk of exposure to the virus. Seven days later, he was tested for SARS-CoV-2 as part of a universal testing campaign at the shelter. His test returned positive for SARS-CoV-2 RNA, confirming a diagnosis of Covid-19.\n\nCOVID-19 (Coronavirus Disease 2019)""
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10.1056/NEJMcpc2002413,Case 20-2020: A 7-Year-Old Girl with Severe Psychological Distress after Family Separation,,Post-traumatic stress disorder.,Post-traumatic stress disorder.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 7-year-old girl who had immigrated to the United States from Central America was evaluated in the asylum clinic of this hospital - where forensic medical evaluations of asylum seekers are performed to document evidence of persecution - because of psychological distress after family separation while in U.S. immigration detention.
Seven months before this evaluation, the patient and her mother fled their village in Central America because of physical and emotional abuse. They traveled by foot, motorcycle, bus, and truck for thousands of kilometers, with limited access to food, water, and other basic resources during their journey. They traveled without legal authorization; on one occasion, they hid in a farmhouse for several days to evade local authorities.
Six months before this evaluation, the patient and her mother crossed the United States-Mexico border. The mother reported that they had been surrounded by border patrol officers and instructed to relinquish personal belongings and remove pieces of clothing; these items were not returned. The patient and her mother were driven to a border detention facility in the Southwest region of the United States and were placed with approximately 40 other women and children in a room that was locked and guarded by male guards. The room had cement floors, a toilet shielded by a partial wall, and a mattress for every four people.
After 2 days of detainment, the patient's mother was instructed to bathe the child, dress her in an oversized, unmarked uniform, and place her in a line of children approximately 5 to 12 years old. The children were led out of the room without their mothers and transported to a facility in another state. The patient and her mother were not informed of the destination or told when they would be able to communicate. The mother was told that she would be deported and would not see her child again.
Five days later, the patient's mother was transported to a facility more than 1000 km away from the patient's new facility. After 15 days of separation, the patient and her mother communicated by telephone for the first time. During the next month, they talked approximately once per week.
The patient described that, while she was in the facility, she was bullied by other children. They called her names, insulted her, and stole a hat that she had made for her mother. A boy hit the patient in the face and loosened a tooth; another child kicked a ball toward her mouth and caused a nosebleed. The patient befriended a girl and cried for days when that girl was transported to another location without notice. When the patient had a fever, cough, and conjunctivitis, she was held in isolation for an unknown amount of time; the symptoms resolved spontaneously. The patient felt uncomfortable with male staff members and requested that female staff members be assigned to care for her; she reported that this request had not been granted.
Four months before this evaluation and approximately 5 weeks after crossing the border, the patient's mother filed for asylum in the United States. She was released and traveled to New England, at which point she petitioned for the release of the patient. After 2 months of separation, the patient was released and transported to New England to join her mother.
During the evaluation in the asylum clinic, the patient's mother reported that the girl no longer had interest in activities that she had previously enjoyed. She had performed well in school but now had trouble focusing during class and had become afraid of other children, especially boys. She had begun to have aggressive behavior - such as throwing rocks at people, cursing, and frequently getting into fights with other children - along with food aversions; the patient now ate only soup from a cup and had no interest in foods she had previously enjoyed.
The patient's mother also reported that the girl had anxiety, which was worse when she was separated from her mother. During these times, the patient had catastrophic thoughts, such as thoughts of her mother dying or being run over by a vehicle. She insisted that her mother walk her to the door of her school every day. At night, she could not fall asleep unless she was holding her mother's hand, and she had frequent nightmares. The patient scratched and kicked during sleep and would awake suddenly, screaming and crying.
The patient had no history of illness and had met normal developmental milestones. She took no medications and had no known drug allergies. She lived with her mother in a suburban area of New England. In Central America, the patient had lived with her parents and grandparents. Her father drank alcohol and used illicit drugs.
The patient reported that, in Central America, ""bad people wanted to kill my mother."" She was aware that her mother had been abducted at gunpoint and held against her will for an extended period. She recalled a burglary of the family's home. The patient had also witnessed her father hitting her mother. She reported that she had heard her father tell her mother that he wished the mother would die. On multiple occasions, he had locked the patient and her mother inside their home for several days while he drank alcohol or used drugs. The father had used a belt to strike the patient.
The patient was well developed and appropriately dressed. She was alert and cooperative but detached. Speech was spontaneous and fluent in Spanish. Mood and affect were normal initially but became more negative during the interview. She became visibly anxious when discussing her childhood in Central America and her detention in the Southwest.
A diagnosis and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 7-year-old girl who had immigrated to the United States from Central America was evaluated in the asylum clinic of this hospital - where forensic medical evaluations of asylum seekers are performed to document evidence of persecution - because of psychological distress after family separation while in U.S. immigration detention.
Seven months before this evaluation, the patient and her mother fled their village in Central America because of physical and emotional abuse. They traveled by foot, motorcycle, bus, and truck for thousands of kilometers, with limited access to food, water, and other basic resources during their journey. They traveled without legal authorization; on one occasion, they hid in a farmhouse for several days to evade local authorities.
Six months before this evaluation, the patient and her mother crossed the United States-Mexico border. The mother reported that they had been surrounded by border patrol officers and instructed to relinquish personal belongings and remove pieces of clothing; these items were not returned. The patient and her mother were driven to a border detention facility in the Southwest region of the United States and were placed with approximately 40 other women and children in a room that was locked and guarded by male guards. The room had cement floors, a toilet shielded by a partial wall, and a mattress for every four people.
After 2 days of detainment, the patient's mother was instructed to bathe the child, dress her in an oversized, unmarked uniform, and place her in a line of children approximately 5 to 12 years old. The children were led out of the room without their mothers and transported to a facility in another state. The patient and her mother were not informed of the destination or told when they would be able to communicate. The mother was told that she would be deported and would not see her child again.
Five days later, the patient's mother was transported to a facility more than 1000 km away from the patient's new facility. After 15 days of separation, the patient and her mother communicated by telephone for the first time. During the next month, they talked approximately once per week.
The patient described that, while she was in the facility, she was bullied by other children. They called her names, insulted her, and stole a hat that she had made for her mother. A boy hit the patient in the face and loosened a tooth; another child kicked a ball toward her mouth and caused a nosebleed. The patient befriended a girl and cried for days when that girl was transported to another location without notice. When the patient had a fever, cough, and conjunctivitis, she was held in isolation for an unknown amount of time; the symptoms resolved spontaneously. The patient felt uncomfortable with male staff members and requested that female staff members be assigned to care for her; she reported that this request had not been granted.
Four months before this evaluation and approximately 5 weeks after crossing the border, the patient's mother filed for asylum in the United States. She was released and traveled to New England, at which point she petitioned for the release of the patient. After 2 months of separation, the patient was released and transported to New England to join her mother.
During the evaluation in the asylum clinic, the patient's mother reported that the girl no longer had interest in activities that she had previously enjoyed. She had performed well in school but now had trouble focusing during class and had become afraid of other children, especially boys. She had begun to have aggressive behavior - such as throwing rocks at people, cursing, and frequently getting into fights with other children - along with food aversions; the patient now ate only soup from a cup and had no interest in foods she had previously enjoyed.
The patient's mother also reported that the girl had anxiety, which was worse when she was separated from her mother. During these times, the patient had catastrophic thoughts, such as thoughts of her mother dying or being run over by a vehicle. She insisted that her mother walk her to the door of her school every day. At night, she could not fall asleep unless she was holding her mother's hand, and she had frequent nightmares. The patient scratched and kicked during sleep and would awake suddenly, screaming and crying.
The patient had no history of illness and had met normal developmental milestones. She took no medications and had no known drug allergies. She lived with her mother in a suburban area of New England. In Central America, the patient had lived with her parents and grandparents. Her father drank alcohol and used illicit drugs.
The patient reported that, in Central America, ""bad people wanted to kill my mother."" She was aware that her mother had been abducted at gunpoint and held against her will for an extended period. She recalled a burglary of the family's home. The patient had also witnessed her father hitting her mother. She reported that she had heard her father tell her mother that he wished the mother would die. On multiple occasions, he had locked the patient and her mother inside their home for several days while he drank alcohol or used drugs. The father had used a belt to strike the patient.
The patient was well developed and appropriately dressed. She was alert and cooperative but detached. Speech was spontaneous and fluent in Spanish. Mood and affect were normal initially but became more negative during the interview. She became visibly anxious when discussing her childhood in Central America and her detention in the Southwest.
A diagnosis and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 7-year-old girl who has experienced significant trauma, including physical and emotional abuse, family separation, and bullying. She is now exhibiting symptoms of psychological distress, including anxiety, nightmares, aggressive behavior, and changes in eating habits. The differential diagnosis for this patient includes post-traumatic stress disorder (PTSD), acute stress disorder, adjustment disorder, and depression. Acute stress disorder is unlikely as the symptoms have persisted for more than a month. Adjustment disorder is also unlikely as the symptoms are severe and include significant distress and impairment. Depression could be a possibility, but the patient's symptoms of nightmares, flashbacks, and severe anxiety are more characteristic of PTSD. Given the patient's history of trauma and her current symptoms, PTSD is the most likely diagnosis.\n\nDiagnosis: Post-Traumatic Stress Disorder (PTSD)""
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10.1056/NEJMcpc2002419,Case 19-2020: A 74-Year-Old Man with Acute Respiratory Failure and Unclear Goals of Care,"Hematocrit (%)   28.5
Hemoglobin (g/dl)   8.8
White‑cell count (per μl)   9900
Differential count (per μl)
Neutrophils   5020
Lymphocytes   3120
Monocytes   1650
Eosinophils   10
Basophils 9–300 20
Platelet count (per μl)   176,000
Sodium (mmol/liter)   134
Potassium (mmol/liter)   5.0
Chloride (mmol/liter)   94
Carbon dioxide (mmol/liter)   27
Anion gap (mmol/liter)   13
Urea nitrogen (mg/dl)   40
Creatinine (mg/dl)   2.09
Glucose (mg/dl)   95
Alanine aminotransferase (U/liter)   17
Aspartate aminotransferase (U/liter)   31
Alkaline phosphatase (U/liter)   72
C‚Äëreactive protein (mg/liter)  .0 38.4
Lactic acid (mmol/liter)   1.9
Lactate dehydrogenase (U/liter) 11 10 262
D‚Äëdimer (ng/ml)   1041",Influenza A virus infection,Influenza A virus infection,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 74-year-old man with mantle-cell lymphoma was admitted to this hospital during the coronavirus disease 2019 (Covid-19) pandemic because of acute respiratory failure.
One day before this admission, productive cough and dyspnea developed. The next day, when the patient was being evaluated at home by a visiting nurse, the oxygen saturation was 85% while he was breathing ambient air. Emergency medical services were called, and on their arrival, treatment with continuous positive airway pressure was initiated. The patient was transported by ambulance to this hospital.
In the emergency department, the patient reported severe shortness of breath. He had no fever, chills, chest pain, abdominal distention, diarrhea, or leg swelling. Additional history was obtained from the patient's wife by telephone. Twenty-three years before this admission, the patient had received a diagnosis of metastatic mantle-cell lymphoma, and several different regimens of chemotherapy had been used for the treatment of progressive disease.
Four years before this admission, gastrointestinal bleeding had occurred because of a duodenal ulcer, resulting in hemorrhagic shock; 3 years before this admission, severe gastrointestinal bleeding had recurred because of an esophageal ulcer. At that time, an inpatient medical team had discussed goals of care with the patient, and a status of ""do not resuscitate"" (DNR) had been assigned.
Three weeks before this admission, the patient had undergone transcatheter mitral valve repair for the treatment of mitral regurgitation. One week later, venetoclax therapy was initiated. Shortness of breath developed, and furosemide was administered. An inpatient medical team discussed goals of care with the patient, who explained that he had agreed to a DNR status several years earlier, when he had been ""very sick and near death"" and ""in a different place""; a new status of ""full code"" was assigned.
The patient had coronary artery disease, hypertension, hyperlipidemia, chronic renal insufficiency, obstructive sleep apnea, and gout. Medications included venetoclax, furosemide, aspirin, atorvastatin, amlodipine, levothyroxine, allopurinol, omeprazole, alfuzosin, finasteride, riboflavin, ascorbic acid, calcium carbonate, and cholecalciferol.
On examination, the patient appeared to be in respiratory distress. The temperature was 35.9[degrees]C, the pulse 98 beats per minute, the blood pressure 129/58 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 97% while he was receiving oxygen through a nonrebreather face mask at a rate of 6 liters per minute; the oxygen saturation decreased to 87% with minimal exertion. Heart sounds were regular, and a systolic murmur was present; both lungs were clear on auscultation. Laboratory test results are shown in Table 1. Radiography of the chest revealed bibasilar patchy and interstitial opacities and small bilateral pleural effusions (Figure 1).	
Table 1
Furosemide, ceftriaxone, azithromycin, and oseltamivir were administered intravenously. Ninety minutes after the patient arrived in the emergency department, the oxygen saturation decreased to 74%, and the rate of supplemental oxygen was increased to 15 liters per minute. Preparations were made for intubation of the trachea and initiation of mechanical ventilation. The emergency department team was concerned about the likelihood of benefit of cardiopulmonary resuscitation (CPR) and intubation; an urgent palliative care consultation was requested
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 74-year-old man with mantle-cell lymphoma was admitted to this hospital during the coronavirus disease 2019 (Covid-19) pandemic because of acute respiratory failure.
One day before this admission, productive cough and dyspnea developed. The next day, when the patient was being evaluated at home by a visiting nurse, the oxygen saturation was 85% while he was breathing ambient air. Emergency medical services were called, and on their arrival, treatment with continuous positive airway pressure was initiated. The patient was transported by ambulance to this hospital.
In the emergency department, the patient reported severe shortness of breath. He had no fever, chills, chest pain, abdominal distention, diarrhea, or leg swelling. Additional history was obtained from the patient's wife by telephone. Twenty-three years before this admission, the patient had received a diagnosis of metastatic mantle-cell lymphoma, and several different regimens of chemotherapy had been used for the treatment of progressive disease.
Four years before this admission, gastrointestinal bleeding had occurred because of a duodenal ulcer, resulting in hemorrhagic shock; 3 years before this admission, severe gastrointestinal bleeding had recurred because of an esophageal ulcer. At that time, an inpatient medical team had discussed goals of care with the patient, and a status of ""do not resuscitate"" (DNR) had been assigned.
Three weeks before this admission, the patient had undergone transcatheter mitral valve repair for the treatment of mitral regurgitation. One week later, venetoclax therapy was initiated. Shortness of breath developed, and furosemide was administered. An inpatient medical team discussed goals of care with the patient, who explained that he had agreed to a DNR status several years earlier, when he had been ""very sick and near death"" and ""in a different place""; a new status of ""full code"" was assigned.
The patient had coronary artery disease, hypertension, hyperlipidemia, chronic renal insufficiency, obstructive sleep apnea, and gout. Medications included venetoclax, furosemide, aspirin, atorvastatin, amlodipine, levothyroxine, allopurinol, omeprazole, alfuzosin, finasteride, riboflavin, ascorbic acid, calcium carbonate, and cholecalciferol.
On examination, the patient appeared to be in respiratory distress. The temperature was 35.9[degrees]C, the pulse 98 beats per minute, the blood pressure 129/58 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 97% while he was receiving oxygen through a nonrebreather face mask at a rate of 6 liters per minute; the oxygen saturation decreased to 87% with minimal exertion. Heart sounds were regular, and a systolic murmur was present; both lungs were clear on auscultation. Laboratory test results are shown in Table 1. Radiography of the chest revealed bibasilar patchy and interstitial opacities and small bilateral pleural effusions (Figure 1).	
Table 1
Furosemide, ceftriaxone, azithromycin, and oseltamivir were administered intravenously. Ninety minutes after the patient arrived in the emergency department, the oxygen saturation decreased to 74%, and the rate of supplemental oxygen was increased to 15 liters per minute. Preparations were made for intubation of the trachea and initiation of mechanical ventilation. The emergency department team was concerned about the likelihood of benefit of cardiopulmonary resuscitation (CPR) and intubation; an urgent palliative care consultation was requested
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 74-year-old man with a history of mantle-cell lymphoma, coronary artery disease, hypertension, hyperlipidemia, chronic renal insufficiency, obstructive sleep apnea, and gout. He presents with acute respiratory failure, productive cough, and dyspnea. The differential diagnosis for this patient includes pneumonia, congestive heart failure, chronic obstructive pulmonary disease (COPD) exacerbation, and COVID-19. \n\nThe patient's chest radiography revealed bibasilar patchy and interstitial opacities and small bilateral pleural effusions, which could be indicative of pneumonia or congestive heart failure. However, the patient's history of heart disease and recent mitral valve repair could also suggest congestive heart failure. The patient's history of obstructive sleep apnea and the absence of wheezing or other signs of COPD on examination make a COPD exacerbation less likely. \n\nGiven the patient's presentation during the COVID-19 pandemic, COVID-19 should also be considered. The patient's symptoms of cough and dyspnea, along with his decreased oxygen saturation, are consistent with COVID-19. Furthermore, the patient's history of mantle-cell lymphoma and recent chemotherapy make him immunocompromised and at higher risk for severe COVID-19. \n\nDiagnosis: COVID-19 is the most likely diagnosis.""
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}",COVID-19,N
10.1056/NEJMcpc2002417,Case 18-2020: A 73-Year-Old Man with Hypoxemic Respiratory Failure and Cardiac Dysfunction,"Hemoglobin (g/dl)   15.7
Hematocrit (%)   44.5
White-cell count (per μl)   18,400
Differential count (%)
Neutrophils   82.2
Lymphocytes   11.4
Monocytes   5.3
Eosinophils   0.0
Platelet count (per μl)   222,000
Sodium (mmol/liter)   138
Potassium (mmol/liter) 3.4–5.4 4.9
Chloride (mmol/liter) 96–108 100
Carbon dioxide (mmol/liter) 22–32 16
Urea nitrogen (mg/dl)   17
Creatinine (mg/dl)   1.8
Calcium (mg/dl) 8.4–10.3 8.0
Alanine aminotransferase (U/liter)   19
Aspartate aminotransferase (U/liter)   88
Creatine kinase (U/liter)   395
Lactate (mmol/liter)   3.5
Troponin T (ng/ml)   4.19
Central venous oxygen saturation (%) 7 0 78
N-terminal pro–B-type natriuretic peptide (pg/ml)  29 1298
Lactate dehydrogenase (U/liter)   572
d-dimer (ng/ml)   3838
C-reactive protein (mg/liter)   118.2
Ferritin (ng/ml) 3 0 2695
Prothrombin time (sec)   15.6
International normalized ratio   1.4
Arterial blood gases
Fraction of inspired oxygen 1.0
pH   7.29
Partial pressure of carbon dioxide (mm Hg)   42
Partial pressure of oxygen (mm Hg)   118",Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with acute respiratory distress syndrome and suspected myopericarditis,"Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in acute respiratory distress syndrome and suspected myopericarditis.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 73-year-old man was transferred to the intensive care unit (ICU) of an academic health center in Boston for acute hypoxemic respiratory failure in March 2020, during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient had been in his usual state of health until 6 days before this transfer, when a dry cough, fever, and worsening fatigue developed. Two days later, his symptoms had not resolved, and he presented to the emergency department at a local hospital. The temperature was 38.8[degrees]C, the blood pressure 94/62 mm Hg, the heart rate 91 beats per minute, the respiratory rate 12 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. On examination, he appeared well, and the lung sounds were clear. The white-cell count was 5600 per microliter (reference range, 4800 to 10,500); 56% of the cells were neutrophils and 33% were lymphocytes. A nasopharyngeal swab was submitted to the Massachusetts State Laboratory for nucleic acid testing for SARS-CoV-2 RNA. Tests for influenza A and B viruses and respiratory syncytial virus were not performed owing to a statewide shortage of nasopharyngeal swabs.
Dr. Diana Litmanovich: Computed tomography (CT) of the chest, performed without the administration of intravenous contrast material, revealed small (1 to 1.5 cm in diameter), rounded central and peripheral ground-glass opacities in both lungs (Figure 1A).	
Figure 1 
Dr. Martin: Oseltamivir was prescribed for the empirical treatment of influenza, and the patient was discharged from the emergency department and instructed to self-quarantine at home. During the next 4 days, his symptoms persisted; when dyspnea developed, he contacted his primary care physician and was referred back to the emergency department at the local hospital. The temperature was 38.6[degrees]C, the blood pressure 158/91 mm Hg, the heart rate 108 beats per minute, the respiratory rate 28 breaths per minute, and the oxygen saturation 90% while he was breathing ambient air. He appeared fatigued, tachypneic, and distressed; auscultation of the lungs revealed decreased breath sounds bilaterally. The trachea was intubated, and mechanical ventilation was initiated. Intravenous propofol, cisatracurium, cefepime, and norepinephrine were administered, and the patient was transferred by helicopter to an academic health center in Boston for further evaluation and management of symptoms.
On the patient's arrival at the academic health center, his family was available to provide information regarding medical history, surgical history, and a recent review of systems by telephone. The review of systems was negative for conjunctivitis, nasal congestion, sinusitis, anosmia, abdominal pain, bloating, diarrhea, light-headedness, dizziness, chest pain, and edema. The patient's status with respect to influenza and pneumococcal vaccination was unknown. His medical history was notable for hypertension, diabetes mellitus, atrial fibrillation, and obstructive sleep apnea, for which nightly continuous positive airway pressure had been prescribed. He had undergone surgical aortic-valve replacement for severe symptomatic aortic stenosis 1 year earlier; there had been no evidence of obstructive coronary artery disease on preoperative angiography. Radiofrequency ablation for recurrent atrial flutter had been performed 2 years earlier, and he had undergone right shoulder arthroplasty. Medications included metformin, insulin lispro, atenolol, losartan, and apixaban. Multiple statin medications had previously caused myalgia with elevated creatine kinase levels.
The patient was a health care worker but had no known sick contacts. No family members were ill. He had not traveled recently or had other environmental exposures. He did not use tobacco, drink alcohol, or use illicit substances. His family history was notable for coronary artery disease in multiple relatives; there was no history of pulmonary disease.
The patient was admitted to a dedicated Covid-19 ICU at the academic health center. The temperature was 38.9[degrees]C, the blood pressure 100/60 mm Hg while he was receiving intravenous norepinephrine, the heart rate 112 beats per minute, the respiratory rate 25 breaths per minute, and the oxygen saturation 95% while he was receiving oxygen through a mechanical ventilator (positive end-expiratory pressure, 5 cm of water; tidal volume, 410 ml; fraction of inspired oxygen, 1.0). The patient was sedated. There was no jugular venous distention. Auscultation of the chest revealed a tachycardic rhythm with no murmur and coarse breath sounds with rhonchi in both lungs. His arms and legs were cool and clammy. The remainder of the examination was normal.
Catheters were placed in the right internal jugular vein and the left radial artery. The central venous pressure was 4 mm Hg. The partial-thromboplastin time and blood levels of phosphorus and magnesium were normal; other laboratory test results are shown in Table 1. A blood sample was obtained for culture, and a nasopharyngeal swab was obtained for nucleic acid testing for the detection of community-acquired respiratory pathogens and SARS-CoV-2 RNA.	
Table 1 
Dr. Litmanovich: An anteroposterior radiograph of the chest (Figure 1B) showed extensive confluent central and peripheral parenchymal opacities in both lungs. The central venous catheter in the right internal jugular vein was in an appropriate position.
Dr. Martin: An electrocardiogram (Figure 2A) showed normal sinus rhythm with left atrial abnormality, a borderline prolonged PR interval, ST-segment depressions of 1 mm in the inferior leads, ST-segment elevations of 1 mm in leads I and aVL, PR-segment deviations (a depression in lead II and an elevation in lead aVR), and a corrected QT (QTc) interval of 425 msec. A transthoracic echocardiogram showed severe global left ventricular hypokinesis, as well as dysfunction of the right ventricular free wall and the apex (see Videos 1 and 2, available with the full text of this article at
NEJM.org
). These findings were new relative to an echocardiogram that had been obtained 2 months earlier as part of routine surveillance after aortic-valve replacement, that had shown normal biventricular function. The size of the left ventricular chamber was normal. There was mild symmetric thickening of the left ventricular wall (12 mm; normal thickness, <=11), a finding that was unchanged from the previous echocardiogram. No evidence of pericardial effusion was observed, and the bioprosthetic aortic valve was well seated and appeared to be functioning normally.	
Figure 2 
The patient received intravenous propofol, fentanyl, midazolam, and cisatracurium, as well as empirical intravenous vancomycin, cefepime, and doxycycline. Treatment with apixaban was discontinued, and intravenous heparin was initiated. Hydroxychloroquine was administered enterally.
Additional management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 73-year-old man was transferred to the intensive care unit (ICU) of an academic health center in Boston for acute hypoxemic respiratory failure in March 2020, during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient had been in his usual state of health until 6 days before this transfer, when a dry cough, fever, and worsening fatigue developed. Two days later, his symptoms had not resolved, and he presented to the emergency department at a local hospital. The temperature was 38.8[degrees]C, the blood pressure 94/62 mm Hg, the heart rate 91 beats per minute, the respiratory rate 12 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. On examination, he appeared well, and the lung sounds were clear. The white-cell count was 5600 per microliter (reference range, 4800 to 10,500); 56% of the cells were neutrophils and 33% were lymphocytes. A nasopharyngeal swab was submitted to the Massachusetts State Laboratory for nucleic acid testing for SARS-CoV-2 RNA. Tests for influenza A and B viruses and respiratory syncytial virus were not performed owing to a statewide shortage of nasopharyngeal swabs.
Dr. Diana Litmanovich: Computed tomography (CT) of the chest, performed without the administration of intravenous contrast material, revealed small (1 to 1.5 cm in diameter), rounded central and peripheral ground-glass opacities in both lungs (Figure 1A).	
Figure 1 
Dr. Martin: Oseltamivir was prescribed for the empirical treatment of influenza, and the patient was discharged from the emergency department and instructed to self-quarantine at home. During the next 4 days, his symptoms persisted; when dyspnea developed, he contacted his primary care physician and was referred back to the emergency department at the local hospital. The temperature was 38.6[degrees]C, the blood pressure 158/91 mm Hg, the heart rate 108 beats per minute, the respiratory rate 28 breaths per minute, and the oxygen saturation 90% while he was breathing ambient air. He appeared fatigued, tachypneic, and distressed; auscultation of the lungs revealed decreased breath sounds bilaterally. The trachea was intubated, and mechanical ventilation was initiated. Intravenous propofol, cisatracurium, cefepime, and norepinephrine were administered, and the patient was transferred by helicopter to an academic health center in Boston for further evaluation and management of symptoms.
On the patient's arrival at the academic health center, his family was available to provide information regarding medical history, surgical history, and a recent review of systems by telephone. The review of systems was negative for conjunctivitis, nasal congestion, sinusitis, anosmia, abdominal pain, bloating, diarrhea, light-headedness, dizziness, chest pain, and edema. The patient's status with respect to influenza and pneumococcal vaccination was unknown. His medical history was notable for hypertension, diabetes mellitus, atrial fibrillation, and obstructive sleep apnea, for which nightly continuous positive airway pressure had been prescribed. He had undergone surgical aortic-valve replacement for severe symptomatic aortic stenosis 1 year earlier; there had been no evidence of obstructive coronary artery disease on preoperative angiography. Radiofrequency ablation for recurrent atrial flutter had been performed 2 years earlier, and he had undergone right shoulder arthroplasty. Medications included metformin, insulin lispro, atenolol, losartan, and apixaban. Multiple statin medications had previously caused myalgia with elevated creatine kinase levels.
The patient was a health care worker but had no known sick contacts. No family members were ill. He had not traveled recently or had other environmental exposures. He did not use tobacco, drink alcohol, or use illicit substances. His family history was notable for coronary artery disease in multiple relatives; there was no history of pulmonary disease.
The patient was admitted to a dedicated Covid-19 ICU at the academic health center. The temperature was 38.9[degrees]C, the blood pressure 100/60 mm Hg while he was receiving intravenous norepinephrine, the heart rate 112 beats per minute, the respiratory rate 25 breaths per minute, and the oxygen saturation 95% while he was receiving oxygen through a mechanical ventilator (positive end-expiratory pressure, 5 cm of water; tidal volume, 410 ml; fraction of inspired oxygen, 1.0). The patient was sedated. There was no jugular venous distention. Auscultation of the chest revealed a tachycardic rhythm with no murmur and coarse breath sounds with rhonchi in both lungs. His arms and legs were cool and clammy. The remainder of the examination was normal.
Catheters were placed in the right internal jugular vein and the left radial artery. The central venous pressure was 4 mm Hg. The partial-thromboplastin time and blood levels of phosphorus and magnesium were normal; other laboratory test results are shown in Table 1. A blood sample was obtained for culture, and a nasopharyngeal swab was obtained for nucleic acid testing for the detection of community-acquired respiratory pathogens and SARS-CoV-2 RNA.	
Table 1 
Dr. Litmanovich: An anteroposterior radiograph of the chest (Figure 1B) showed extensive confluent central and peripheral parenchymal opacities in both lungs. The central venous catheter in the right internal jugular vein was in an appropriate position.
Dr. Martin: An electrocardiogram (Figure 2A) showed normal sinus rhythm with left atrial abnormality, a borderline prolonged PR interval, ST-segment depressions of 1 mm in the inferior leads, ST-segment elevations of 1 mm in leads I and aVL, PR-segment deviations (a depression in lead II and an elevation in lead aVR), and a corrected QT (QTc) interval of 425 msec. A transthoracic echocardiogram showed severe global left ventricular hypokinesis, as well as dysfunction of the right ventricular free wall and the apex (see Videos 1 and 2, available with the full text of this article at
NEJM.org
). These findings were new relative to an echocardiogram that had been obtained 2 months earlier as part of routine surveillance after aortic-valve replacement, that had shown normal biventricular function. The size of the left ventricular chamber was normal. There was mild symmetric thickening of the left ventricular wall (12 mm; normal thickness, <=11), a finding that was unchanged from the previous echocardiogram. No evidence of pericardial effusion was observed, and the bioprosthetic aortic valve was well seated and appeared to be functioning normally.	
Figure 2 
The patient received intravenous propofol, fentanyl, midazolam, and cisatracurium, as well as empirical intravenous vancomycin, cefepime, and doxycycline. Treatment with apixaban was discontinued, and intravenous heparin was initiated. Hydroxychloroquine was administered enterally.
Additional management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 73-year-old man who presented with a dry cough, fever, fatigue, and worsening dyspnea. His symptoms began 6 days prior to admission. He has a history of hypertension, diabetes mellitus, atrial fibrillation, and obstructive sleep apnea. He is also a healthcare worker. His symptoms and the timing of his presentation (March 2020) coincide with the COVID-19 pandemic. His CT scan showed small, rounded central and peripheral ground-glass opacities in both lungs, a common finding in COVID-19 patients. His nasopharyngeal swab was submitted for nucleic acid testing for SARS-CoV-2 RNA. Given the patient's symptoms, history, and imaging findings, the most likely diagnosis is COVID-19. Other possibilities could include other viral pneumonias, bacterial pneumonia, or non-infectious causes of lung injury, but these are less likely given the clinical context.\n\nDiagnosis: COVID-19 (SARS-CoV-2 infection)""
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10.1056/NEJMcpc2002418,Case 17-2020: A 68-Year-Old Man with Covid-19 and Acute Kidney Injury,"Hematocrit (%)   39.8 27.9 26.3
Hemoglobin (g/dl)   12.4 8.6 8.0
White cells (per μl)   10,710 12,430 11,540
Differential count (per μl)
Neutrophils   9600 9160 9090
Lymphocytes   660 1390 1340
Monocytes   340 1300 810
Eosinophils   10 360 230
Platelets   304,000 403,000 307,000
Prothrombin time (sec)   15.2 16.4 15.4
Prothrombin-time international 
normalized ratio
  1.2 1.3 1.2
Activated partial-thromboplastin 
time (sec)
22–35 NA 36.3 27.5
Sodium (mmol/liter)   134 143 148
Potassium (mmol/liter)   5.4 3.8 3.9
Chloride (mmol/liter)   96 101 111
Carbon dioxide (mmol/liter) 23. 1.9 17 16 19
Urea nitrogen (mg/dl)   17 111 109
Creatinine (mg/dl)   1.3 6.9 3.6
Glucose (mg/dl)   234 159 273
d-dimer (ng/ml)   1515 8322 5666
Ferritin (μg/liter) 2 00 367 434 280
Lactate dehydrogenase (U/liter) 11 10 482 354 306
C-reactive protein (mg/liter)   397.5 136.6 41.0
Creatine kinase (U/liter)   184 57 135
Urine
Bilirubin Negative Negative Negative Negative
Blood Negative 2+ 1+ 2+
Clarity Clear Turbid Turbid Turbid
Glucose Negative 3+ 1+ Negative
Ketones Negative 2+ Negative Negative
pH   5.5 5.0 5.0
Protein Negative 2+ 1+ 1+
Specific gravity   1.020 1.014 1.016
Red cells (per high-power field)   None 5–10  
White cells (per high-power field)        ",Acute kidney injury in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection,Acute kidney injury in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old man was admitted to this hospital with fever, shortness of breath, and acute kidney injury during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient had been in his usual state of health until 4 days before admission, when fever developed, with a temperature of up to 39.9[degrees]C and associated shaking chills. He had a poor appetite and was eating and drinking less than usual. Three days before admission, he stopped using long-acting insulin for his diabetes because fasting blood glucose levels were less than 100 mg per deciliter (5.6 mmol per liter; reference range, 70 to 99 mg per deciliter [3.9 to 5.5 mmol per liter]). One day before admission, a dry cough developed. On the morning of admission, the patient noticed shortness of breath. He called his primary care physician, who recommended that he present to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported ongoing shortness of breath, with no chest pain, orthopnea, or leg swelling. He had not traveled recently. He worked as a limousine driver but had not had known contact with anyone with confirmed SARS-CoV-2 infection.
The patient had a history of diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and obstructive sleep apnea. A drug-eluting stent had been placed in the left anterior descending coronary artery 7 years earlier. Medications included aspirin, clopidogrel, dulaglutide, empagliflozin, ezetimibe, glipizide, insulin glargine, lisinopril, metformin, metoprolol, rosuvastatin, and testosterone. There were no known drug allergies. The patient did not smoke, drink alcohol, or use illicit substances. He lived with his girlfriend in a suburb of Boston. His family history included coronary artery disease in his father and emphysema in his mother.
On examination, the temperature was 37.6[degrees]C, the blood pressure 157/74 mm Hg, the heart rate 124 beats per minute, the respiratory rate 40 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 37.1. The patient had moderately increased work of breathing and diffuse coarse crackles at the lung bases. The mucous membranes were dry. The remainder of the physical examination was normal. The blood creatinine level of 1.3 mg per deciliter (115 [mu]mol per liter; reference range, 0.6 to 1.5 mg per deciliter [53 to 133 [mu]mol per liter]) was higher than the level obtained 1 year earlier (0.8 mg per deciliter [71 [mu]mol per liter]). Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Jo-Anne O. Shepard: A chest radiograph obtained in the emergency department showed bilateral multifocal patchy opacities, a finding suggestive of pneumonia (Figure 1A).	
Figure 1 
Dr. Baggett: Blood samples were obtained for culture, and a nasopharyngeal swab was submitted to be tested for SARS-CoV-2 RNA. Two liters of intravenous lactated Ringer's solution were administered, along with ceftriaxone and azithromycin. The patient was admitted to the hospital.
Three hours after admission, the oxygen saturation decreased to 87% while the patient was breathing ambient air and then increased to 92% with the administration of oxygen through a nasal cannula at a rate of 2 liters per minute. Five hours later, shortness of breath increased and the oxygen saturation decreased, and the oxygen flow rate was adjusted to 6 liters per minute. The patient was transferred to the intensive care unit (ICU). Intravenous vancomycin and furosemide were administered. The nucleic acid test for SARS-CoV-2 RNA returned positive. Treatment with hydroxychloroquine was started, and the patient was enrolled in a placebo-controlled clinical trial of remdesivir (ClinicalTrials.gov number, NCT04280705).
Sixteen hours after transfer to the ICU, the patient underwent intubation and mechanical ventilation for persistent tachypnea and worsening oxygen saturation. During the next 24 hours, hypotension developed, with the blood pressure decreasing to 78/45 mm Hg, and treatment with intravenous norepinephrine was initiated. On hospital day 3, the creatinine level increased to 1.8 mg per deciliter (159 [mu]mol per liter), and the patient's participation in the clinical trial of remdesivir was discontinued. During the next 5 days, his urine output was maintained at 100 ml per hour with the administration of increased doses of intravenous loop diuretics, but the blood urea nitrogen and creatinine levels continued to rise - reaching 111 mg per deciliter (39.6 mmol per liter; reference range, 8 to 25 mg per deciliter [2.9 to 8.9 mmol per liter]) and 6.9 mg per deciliter (610 [mu]mol per liter), respectively - and a mixed metabolic and respiratory acidosis developed. Management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old man was admitted to this hospital with fever, shortness of breath, and acute kidney injury during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient had been in his usual state of health until 4 days before admission, when fever developed, with a temperature of up to 39.9[degrees]C and associated shaking chills. He had a poor appetite and was eating and drinking less than usual. Three days before admission, he stopped using long-acting insulin for his diabetes because fasting blood glucose levels were less than 100 mg per deciliter (5.6 mmol per liter; reference range, 70 to 99 mg per deciliter [3.9 to 5.5 mmol per liter]). One day before admission, a dry cough developed. On the morning of admission, the patient noticed shortness of breath. He called his primary care physician, who recommended that he present to the emergency department of this hospital for further evaluation.
In the emergency department, the patient reported ongoing shortness of breath, with no chest pain, orthopnea, or leg swelling. He had not traveled recently. He worked as a limousine driver but had not had known contact with anyone with confirmed SARS-CoV-2 infection.
The patient had a history of diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and obstructive sleep apnea. A drug-eluting stent had been placed in the left anterior descending coronary artery 7 years earlier. Medications included aspirin, clopidogrel, dulaglutide, empagliflozin, ezetimibe, glipizide, insulin glargine, lisinopril, metformin, metoprolol, rosuvastatin, and testosterone. There were no known drug allergies. The patient did not smoke, drink alcohol, or use illicit substances. He lived with his girlfriend in a suburb of Boston. His family history included coronary artery disease in his father and emphysema in his mother.
On examination, the temperature was 37.6[degrees]C, the blood pressure 157/74 mm Hg, the heart rate 124 beats per minute, the respiratory rate 40 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 37.1. The patient had moderately increased work of breathing and diffuse coarse crackles at the lung bases. The mucous membranes were dry. The remainder of the physical examination was normal. The blood creatinine level of 1.3 mg per deciliter (115 [mu]mol per liter; reference range, 0.6 to 1.5 mg per deciliter [53 to 133 [mu]mol per liter]) was higher than the level obtained 1 year earlier (0.8 mg per deciliter [71 [mu]mol per liter]). Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Jo-Anne O. Shepard: A chest radiograph obtained in the emergency department showed bilateral multifocal patchy opacities, a finding suggestive of pneumonia (Figure 1A).	
Figure 1 
Dr. Baggett: Blood samples were obtained for culture, and a nasopharyngeal swab was submitted to be tested for SARS-CoV-2 RNA. Two liters of intravenous lactated Ringer's solution were administered, along with ceftriaxone and azithromycin. The patient was admitted to the hospital.
Three hours after admission, the oxygen saturation decreased to 87% while the patient was breathing ambient air and then increased to 92% with the administration of oxygen through a nasal cannula at a rate of 2 liters per minute. Five hours later, shortness of breath increased and the oxygen saturation decreased, and the oxygen flow rate was adjusted to 6 liters per minute. The patient was transferred to the intensive care unit (ICU). Intravenous vancomycin and furosemide were administered. The nucleic acid test for SARS-CoV-2 RNA returned positive. Treatment with hydroxychloroquine was started, and the patient was enrolled in a placebo-controlled clinical trial of remdesivir (ClinicalTrials.gov number, NCT04280705).
Sixteen hours after transfer to the ICU, the patient underwent intubation and mechanical ventilation for persistent tachypnea and worsening oxygen saturation. During the next 24 hours, hypotension developed, with the blood pressure decreasing to 78/45 mm Hg, and treatment with intravenous norepinephrine was initiated. On hospital day 3, the creatinine level increased to 1.8 mg per deciliter (159 [mu]mol per liter), and the patient's participation in the clinical trial of remdesivir was discontinued. During the next 5 days, his urine output was maintained at 100 ml per hour with the administration of increased doses of intravenous loop diuretics, but the blood urea nitrogen and creatinine levels continued to rise - reaching 111 mg per deciliter (39.6 mmol per liter; reference range, 8 to 25 mg per deciliter [2.9 to 8.9 mmol per liter]) and 6.9 mg per deciliter (610 [mu]mol per liter), respectively - and a mixed metabolic and respiratory acidosis developed. Management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with fever, shortness of breath, and acute kidney injury. He had a history of diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and obstructive sleep apnea. His symptoms started with fever and shaking chills, followed by a dry cough and shortness of breath. He had not traveled recently and had no known contact with anyone with confirmed SARS-CoV-2 infection. However, a nasopharyngeal swab tested positive for SARS-CoV-2 RNA. His condition worsened, requiring intubation and mechanical ventilation. His creatinine levels increased, indicating worsening kidney function. All these symptoms and test results are consistent with severe COVID-19 infection.\n\nDiagnosis: Severe COVID-19 infection.""
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        ""content"": ""The patient presented with fever, shortness of breath, and acute kidney injury. He had a history of diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and obstructive sleep apnea. His symptoms started with fever and shaking chills, followed by a dry cough and shortness of breath. He tested positive for SARS-CoV-2 RNA, indicating a COVID-19 infection. His condition worsened, requiring intubation and mechanical ventilation. His creatinine levels increased, indicating worsening kidney function. \n\nCOVID-19 infection.""
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        ""content"": ""The patient is a 68-year-old man with a history of diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and obstructive sleep apnea. He presented with fever, shortness of breath, and acute kidney injury. The differential diagnosis for this patient includes bacterial pneumonia, viral pneumonia (including COVID-19), congestive heart failure, and acute respiratory distress syndrome (ARDS). The patient's chest radiograph showed bilateral multifocal patchy opacities, which is suggestive of pneumonia. His nasopharyngeal swab tested positive for SARS-CoV-2 RNA, confirming a diagnosis of COVID-19. The patient's worsening respiratory status, requiring intubation and mechanical ventilation, is consistent with severe COVID-19 infection, which can cause ARDS. The patient's increasing creatinine levels and decreasing urine output suggest acute kidney injury, which can be a complication of severe COVID-19. \n\nDiagnosis: Severe COVID-19 infection with acute respiratory distress syndrome and acute kidney injury.""
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10.1056/NEJMcpc1916258,Case 16-2020: A 47-Year-Old Woman with Recurrent Melanoma and Pulmonary Nodules,,Pulmonary histoplasmosis.,Histoplasmosis in the setting of Metastatic melanoma.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 47-year-old woman with malignant melanoma was seen in the pulmonary clinic of this hospital because of new abnormal findings on chest imaging.
The patient had observed routine quarterly surveillance imaging after resection of right axillary melanoma, radiation therapy, and initiation of pembrolizumab therapy 3 years earlier. The most recent imaging was performed 6 days before this evaluation.
Dr. Jo-Anne O. Shepard: Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, revealed a patchy consolidation in the left upper lobe, bilateral hilar and mediastinal lymphadenopathy, and numerous bilateral scattered solid pulmonary nodules with associated ground-glass halos (Figure 1A through 1D). These findings were new relative to the most recent imaging performed 3 months earlier. Other pulmonary nodules, measuring 2 to 4 mm in greatest dimension, in the right upper lobe that had been noted on imaging studies obtained during the previous 3 years were stable. Changes in the right upper lobe that had resulted from radiation therapy were also stable relative to previous imaging studies. CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a hemangioma in the right hepatic lobe that measured 9 mm in greatest dimension and a cyst in the left hepatic lobe that measured 15 mm in diameter; both were unchanged from previous imaging studies. Magnetic resonance imaging (MRI) of the head, performed after the administration of intravenous contrast material, was normal.	
Figure 1
Dr. Cohen: The patient was referred by her oncologist for urgent evaluation in the pulmonary clinic of this hospital. On evaluation, the patient reported no symptoms, specifically no fever, weight loss, night sweats, fatigue, malaise, headache, chest pain, cough, hemoptysis, new or changed skin lesions (except a mild traumatic abrasion on the right arm), pruritus, or new masses.
The patient's medical history was notable for superficial spreading melanoma on the right upper back that had initially been diagnosed two decades before this evaluation and had been surgically excised, with clear pathological margins. Eleven years later, an in situ superficial spreading melanoma developed on the left upper back and was completely excised.
Dr. Shepard: Three years before the current evaluation, locally advanced melanoma in the right axilla was diagnosed on the basis of a positron-emission tomographic and CT image that showed a 3.5-cm right axillary nodal conglomerate mass with multiple foci of intense 18F-fluorodeoxyglucose (FDG) uptake; no other sites of FDG avidity were seen (Figure 1E and 1F). Multiple pulmonary nodules, measuring 2 to 4 mm in greatest dimension, in the right lobe and hypodense hepatic lesions, measuring 9 mm in the right lobe and 10 mm in the left lobe, were noted. MRI of the abdomen suggested that the hepatic lesion in the right lobe corresponded to a hemangioma and the hepatic lesion in the left lobe a cyst. MRI of the head, performed before and after the administration of intravenous contrast material, was normal.
Dr. Cohen: At that time, dissection of the right axillary lymph nodes was performed, and examination of the specimens revealed metastatic melanoma in 25 of 39 lymph nodes, with a high degree of extracapsular extension. Molecular profiling identified the BRAF V600E mutation. The patient received radiation therapy to the right axilla and supraclavicular fossa (total dose of 4800 cGy over a period of 5 weeks), followed by pembrolizumab every 3 weeks for the next 12 months. During this course of treatment, lichenoid nodules developed on the fingers of both hands, tenosynovitis developed in the right ankle, and hypothyroidism was diagnosed, for which treatment with levothyroxine was initiated. These findings were attributed to adverse effects of the immune checkpoint inhibitor therapy. The plan for surveillance imaging included CT of the chest, abdomen, and pelvis, which was to be performed every 3 months, and MRI of the head, which was to be performed annually.
The patient's medical history also included bilateral ovarian cysts, osteopenia, and a melanocytoma of the left optic disc that had been stable for at least 13 years. A Papanicolaou smear and testing for high-risk human papillomavirus performed 3 years before this evaluation had been negative. Routine screening mammography performed 1 month before this evaluation had revealed dense breast tissue with bilateral calcifications that appeared to be benign; no suspicious lesions were noted. Medications included calcium carbonate, cholecalciferol, and levothyroxine. There were no known drug allergies.
The patient was born on the northern coast of South America and had immigrated to the United States as a child. She lived in New England with her husband, two children, and two cats. She worked in the health care industry. She drank one or two glasses of wine per day and did not smoke tobacco or use illicit drugs. One month before this evaluation, she and her family had traveled to the northern coast of South America for 1 week. On the trip, the patient spent most her time outdoors, including taking trips to the jungle and swimming in fresh water, and ate local cuisine, such as water chestnuts. When she returned home with her family, her husband and one of her children had generalized myalgias and malaise that resolved spontaneously.
The patient's mother had breast cancer, melanoma, and basal-cell carcinoma; her father had prostate cancer; and her daughter had mixed connective-tissue disease. Her maternal grandfather had colon cancer, her paternal grandmother had breast cancer, and her maternal cousin had melanoma.
On examination, the temperature was 37.0[degrees]C, the blood pressure 123/68 mm Hg, the pulse 56 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 20.8. She appeared well, and the lungs were clear on auscultation. Examination showed fair skin, multiple nevi without suspicious features, and healed scars at the sites of previous surgical procedures. There were lichenoid nodules on the fingers of both hands. The remainder of the physical examination was normal.
The levels of electrolytes, glucose, and lactate dehydrogenase were normal, as were results of renal- and liver-function tests. The complete blood count and differential count were also normal. Blood samples were obtained for culture. An interferon-[gamma] release assay for Mycobacterium tuberculosis was negative, and the level of 1,3-[beta]-D-glucan was less than 31 pg per milliliter (reference value, <60).
Diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 47-year-old woman with malignant melanoma was seen in the pulmonary clinic of this hospital because of new abnormal findings on chest imaging.
The patient had observed routine quarterly surveillance imaging after resection of right axillary melanoma, radiation therapy, and initiation of pembrolizumab therapy 3 years earlier. The most recent imaging was performed 6 days before this evaluation.
Dr. Jo-Anne O. Shepard: Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, revealed a patchy consolidation in the left upper lobe, bilateral hilar and mediastinal lymphadenopathy, and numerous bilateral scattered solid pulmonary nodules with associated ground-glass halos (Figure 1A through 1D). These findings were new relative to the most recent imaging performed 3 months earlier. Other pulmonary nodules, measuring 2 to 4 mm in greatest dimension, in the right upper lobe that had been noted on imaging studies obtained during the previous 3 years were stable. Changes in the right upper lobe that had resulted from radiation therapy were also stable relative to previous imaging studies. CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a hemangioma in the right hepatic lobe that measured 9 mm in greatest dimension and a cyst in the left hepatic lobe that measured 15 mm in diameter; both were unchanged from previous imaging studies. Magnetic resonance imaging (MRI) of the head, performed after the administration of intravenous contrast material, was normal.	
Figure 1
Dr. Cohen: The patient was referred by her oncologist for urgent evaluation in the pulmonary clinic of this hospital. On evaluation, the patient reported no symptoms, specifically no fever, weight loss, night sweats, fatigue, malaise, headache, chest pain, cough, hemoptysis, new or changed skin lesions (except a mild traumatic abrasion on the right arm), pruritus, or new masses.
The patient's medical history was notable for superficial spreading melanoma on the right upper back that had initially been diagnosed two decades before this evaluation and had been surgically excised, with clear pathological margins. Eleven years later, an in situ superficial spreading melanoma developed on the left upper back and was completely excised.
Dr. Shepard: Three years before the current evaluation, locally advanced melanoma in the right axilla was diagnosed on the basis of a positron-emission tomographic and CT image that showed a 3.5-cm right axillary nodal conglomerate mass with multiple foci of intense 18F-fluorodeoxyglucose (FDG) uptake; no other sites of FDG avidity were seen (Figure 1E and 1F). Multiple pulmonary nodules, measuring 2 to 4 mm in greatest dimension, in the right lobe and hypodense hepatic lesions, measuring 9 mm in the right lobe and 10 mm in the left lobe, were noted. MRI of the abdomen suggested that the hepatic lesion in the right lobe corresponded to a hemangioma and the hepatic lesion in the left lobe a cyst. MRI of the head, performed before and after the administration of intravenous contrast material, was normal.
Dr. Cohen: At that time, dissection of the right axillary lymph nodes was performed, and examination of the specimens revealed metastatic melanoma in 25 of 39 lymph nodes, with a high degree of extracapsular extension. Molecular profiling identified the BRAF V600E mutation. The patient received radiation therapy to the right axilla and supraclavicular fossa (total dose of 4800 cGy over a period of 5 weeks), followed by pembrolizumab every 3 weeks for the next 12 months. During this course of treatment, lichenoid nodules developed on the fingers of both hands, tenosynovitis developed in the right ankle, and hypothyroidism was diagnosed, for which treatment with levothyroxine was initiated. These findings were attributed to adverse effects of the immune checkpoint inhibitor therapy. The plan for surveillance imaging included CT of the chest, abdomen, and pelvis, which was to be performed every 3 months, and MRI of the head, which was to be performed annually.
The patient's medical history also included bilateral ovarian cysts, osteopenia, and a melanocytoma of the left optic disc that had been stable for at least 13 years. A Papanicolaou smear and testing for high-risk human papillomavirus performed 3 years before this evaluation had been negative. Routine screening mammography performed 1 month before this evaluation had revealed dense breast tissue with bilateral calcifications that appeared to be benign; no suspicious lesions were noted. Medications included calcium carbonate, cholecalciferol, and levothyroxine. There were no known drug allergies.
The patient was born on the northern coast of South America and had immigrated to the United States as a child. She lived in New England with her husband, two children, and two cats. She worked in the health care industry. She drank one or two glasses of wine per day and did not smoke tobacco or use illicit drugs. One month before this evaluation, she and her family had traveled to the northern coast of South America for 1 week. On the trip, the patient spent most her time outdoors, including taking trips to the jungle and swimming in fresh water, and ate local cuisine, such as water chestnuts. When she returned home with her family, her husband and one of her children had generalized myalgias and malaise that resolved spontaneously.
The patient's mother had breast cancer, melanoma, and basal-cell carcinoma; her father had prostate cancer; and her daughter had mixed connective-tissue disease. Her maternal grandfather had colon cancer, her paternal grandmother had breast cancer, and her maternal cousin had melanoma.
On examination, the temperature was 37.0[degrees]C, the blood pressure 123/68 mm Hg, the pulse 56 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 20.8. She appeared well, and the lungs were clear on auscultation. Examination showed fair skin, multiple nevi without suspicious features, and healed scars at the sites of previous surgical procedures. There were lichenoid nodules on the fingers of both hands. The remainder of the physical examination was normal.
The levels of electrolytes, glucose, and lactate dehydrogenase were normal, as were results of renal- and liver-function tests. The complete blood count and differential count were also normal. Blood samples were obtained for culture. An interferon-[gamma] release assay for Mycobacterium tuberculosis was negative, and the level of 1,3-[beta]-D-glucan was less than 31 pg per milliliter (reference value, <60).
Diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""Pulmonary Paracoccidioidomycosis\n\nThe patient's history of travel to South America, specifically spending time in the jungle and swimming in fresh water, raises the possibility of a fungal infection. The CT scan shows patchy consolidation in the left upper lobe, bilateral hilar and mediastinal lymphadenopathy, and numerous bilateral scattered solid pulmonary nodules with associated ground-glass halos. These findings are consistent with a fungal infection, such as Paracoccidioidomycosis, which is endemic in South America. The patient's lack of response to pembrolizumab therapy and the new findings on imaging also suggest an infectious process rather than progression of her melanoma. The negative interferon-[gamma] release assay for Mycobacterium tuberculosis and the normal level of 1,3-[beta]-D-glucan further support a diagnosis of fungal infection rather than tuberculosis or a bacterial infection.""
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}","{
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        ""role"": ""assistant"",
        ""content"": ""The patient has a history of malignant melanoma and is currently on pembrolizumab therapy. The new findings on chest imaging, including patchy consolidation in the left upper lobe, bilateral hilar and mediastinal lymphadenopathy, and numerous bilateral scattered solid pulmonary nodules with associated ground-glass halos, are suggestive of a pulmonary infection or metastasis. However, the patient is asymptomatic and has no fever, weight loss, night sweats, fatigue, malaise, headache, chest pain, cough, hemoptysis, new or changed skin lesions, pruritus, or new masses. The patient's history of melanoma and current immunotherapy treatment with pembrolizumab, which can cause immune-related adverse effects including pneumonitis, suggest that the new findings on chest imaging could be due to pembrolizumab-induced pneumonitis. \n\nDiagnosis: Pembrolizumab-induced pneumonitis.""
      },
      ""finish_reason"": ""stop""
    }
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  ""usage"": {
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}",Pembrolizumab-induced pneumonitis,N,"{
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  ""created"": 1690702621,
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        ""content"": ""The patient is a 47-year-old woman with a history of malignant melanoma who presents with new abnormal findings on chest imaging. The differential diagnosis for this patient includes metastatic melanoma, infectious pneumonia, and drug-induced pneumonitis. The patient has a history of malignant melanoma, which increases the likelihood of metastatic disease. However, the patient has been on pembrolizumab therapy for 3 years, which can cause drug-induced pneumonitis. The patient also recently traveled to the northern coast of South America, which could expose her to infectious agents causing pneumonia. However, the patient is asymptomatic, which makes infectious pneumonia less likely. The patient's imaging shows a patchy consolidation in the left upper lobe, bilateral hilar and mediastinal lymphadenopathy, and numerous bilateral scattered solid pulmonary nodules with associated ground-glass halos. These findings are new compared to imaging from 3 months ago. This rapid progression of disease is more consistent with drug-induced pneumonitis than metastatic melanoma, which would likely show a more gradual progression. Furthermore, the patient's other pulmonary nodules have been stable for the past 3 years, which also suggests that the new findings are not due to metastatic disease. \n\nDiagnosis: Drug-induced pneumonitis due to pembrolizumab therapy.""
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}",Drug-induced pneumonitis due to pembrolizumab therapy,N
10.1056/NEJMcpc1913477,Case 15-2020: A 79-Year-Old Man with Hyponatremia and Involuntary Movements of the Arm and Face,"Hematocrit (%)   35.6 35
Hemoglobin (g/dl)   12.8 12.4
White-cell count (per μl)   9900 9500
Differential count (per μl)
Neutrophils   7010 6710
Lymphocytes   1270 1490
Monocytes   1340 1080
Eosinophils   130 100
Basophils  00 40 30
Platelet count (per μl)   329,000 284,000
Red-cell count (per μl)   4,120,000 4,000,000
Mean corpuscular volume (fl)   86.4 87.5
Mean corpuscular hemoglobin (pg) 26–34 31.1 31.0
Mean corpuscular hemoglobin level (g/dl) 31–37 36 35.4
Sodium (mmol/liter)   123 123
Potassium (mmol/liter)   4.5 4.5
Chloride (mmol/liter)   85 85
Carbon dioxide (mmol/liter)   24 26
Calcium (mg/dl)   9.5 9.4
Magnesium (mg/dl)   1.8 1.5
Glucose (mg/dl)   111 103
Urea nitrogen (mg/dl)   16 14
Creatinine (mg/dl)   1.05 0.89
Uric acid (mg/dl) 3.6–8.5 NA 3.1
Osmolality in serum (mOsm/kg of water) 28 96 NA 256
Osmolality in randomly obtained urine 
(mOsm/kg of water)
15 50 294 720
Sodium in randomly obtained urine (mmol/
liter)
NA 45 124",LGI1 autoimmune encephalitis.,"Encephalitis associated with LGI1 (leucine-rich, glioma-inactivated 1) antibodies.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 79-year-old man was admitted to this hospital because of hyponatremia and involuntary movements of the arm and face.
The patient had been in his usual state of health and walking 3 miles per day until 5 weeks before the current admission, when fatigue developed. During his daily walks, he began resting after walking a quarter mile because of fatigue; there was no chest pain, dyspnea, or leg pain. In addition, he began taking naps during the day, which was unusual for him. Three weeks before the current admission, the patient presented to his primary care provider for evaluation. Laboratory studies reportedly revealed hyponatremia. He was advised to present to the emergency department of this hospital for further evaluation and treatment.
In the emergency department, the patient reported no history of orthopnea or leg swelling, although his weight had increased by 2.2 kg during the past year. He reported eating and drinking normally, with no nausea, vomiting, or diarrhea. He had no weakness, loss of sensation, headache, or vision changes. Other medical history was notable for hypertension and hyperlipidemia. Medications included lisinopril, hydrochlorothiazide, and atorvastatin; there were no known allergies to medications. He had smoked tobacco in the past but had quit 40 years earlier; he drank alcohol rarely and did not use illicit drugs. He was a retired teacher and lived with his wife in New England. His family history included heart disease in his father and pancreatic cancer in his mother.
The temperature was 36.8[degrees]C, the blood pressure 156/76 mm Hg, the pulse 56 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 74.8 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.4. The physical examination was normal.
The blood sodium level was 123 mmol per liter (reference range, 135 to 145); other laboratory test results are shown in Table 1. The patient received 250 ml of intravenous isotonic fluids. Four hours later, the blood sodium level was 127 mmol per liter. The patient was instructed to stop taking hydrochlorothiazide and to follow up with his primary care physician; he was discharged from the emergency department.	
Table 1
After the patient returned home, his fatigue diminished. One week later, involuntary movements in the left arm and hand developed. The patient described the movements as spasms that caused the arm to flex at the elbow or wrist. The episodes lasted less than 5 seconds and occurred multiple times per day. They often occurred after position changes or sudden movements and often caused him to drop any object he was holding in his left hand. He described feeling a strange sensation immediately before the movements but being unable to suppress them. The patient's wife had noticed that occasionally during the involuntary movements of the left arm and hand, the left side of the patient's face pulled to the side as though he were grimacing. The episodes increased in frequency during the next 2 weeks, and 3 weeks after discharge from the emergency department, the patient returned to this hospital for additional evaluation.
On evaluation, the patellar reflexes were 3+; the remainder of the physical examination was normal. The blood sodium level was 123 mmol per liter. Other laboratory test results are shown in Table 1. Blood levels of thyrotropin and N-terminal pro-B-type natriuretic peptide were normal. The blood cortisol level was 13.5 [mu]g per deciliter; 30 minutes after the administration of 250 [mu]g of cosyntropin, the blood cortisol level was 27.9 [mu]g per deciliter. The patient received 1 liter of intravenous isotonic fluids. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed mild, scattered, nonspecific hypoattenuation of the periventricular and subcortical white matter bilaterally. The patient was admitted to the hospital for further evaluation.
Ten hours later, the blood sodium level was 121 mmol per liter. The patient was asked to limit his intake of water to less than 1 liter per day, and sodium chloride tablets were administered. Twelve hours later, the blood sodium level was 123 mmol per liter. A single, unwitnessed episode of involuntary movement of the left arm and left side of the face occurred.
On the second and third hospital days, intravenous desmopressin and hypertonic fluids were administered, and the blood sodium level gradually increased to 132 mmol per liter. Additional imaging studies were obtained. Magnetic resonance imaging of the head was performed before and after the administration of intravenous contrast material; T2-weighted, fluid-attenuated inversion recovery images showed mild, scattered hyperintensities in the periventricular and subcortical white matter. CT of the chest, abdomen, and pelvis was performed after the administration of intravenous contrast material; the scan showed a small cluster of nodules and linear opacities in the right middle lobe and multilevel degenerative changes of the lumbar spine and bilateral hip joints.
On the fourth hospital day, the administration of intravenous hypertonic fluids and desmopressin was stopped, oral furosemide was added, and sodium chloride tablets were continued. Over the next 3 days, the blood sodium level increased to 137 mmol per liter. The patient was discharged home on the seventh hospital day having had no additional episodes of involuntary movements.
The blood sodium level was normal 2 days after discharge and again 8 days after discharge. The patient was instructed to drink water when he was thirsty without limiting his daily intake. Two weeks after discharge, the patient noticed recurrence of the involuntary movements of the left arm and left side of the face. He was evaluated by his primary care physician. The physical examination was normal, and no involuntary movements were observed. The blood sodium level was 134 mmol per liter. The patient was instructed to limit his intake of water to 2 liters per day.
Four weeks after discharge, the patient was evaluated in the nephrology clinic of this hospital. He reported that the involuntary movements of the left arm and left side of the face had increased in frequency, occurring once per hour. The blood sodium level was 134 mmol per liter. He was referred to the neurology clinic of this hospital for further evaluation. At the neurology clinic, a diagnostic test was performed, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 79-year-old man was admitted to this hospital because of hyponatremia and involuntary movements of the arm and face.
The patient had been in his usual state of health and walking 3 miles per day until 5 weeks before the current admission, when fatigue developed. During his daily walks, he began resting after walking a quarter mile because of fatigue; there was no chest pain, dyspnea, or leg pain. In addition, he began taking naps during the day, which was unusual for him. Three weeks before the current admission, the patient presented to his primary care provider for evaluation. Laboratory studies reportedly revealed hyponatremia. He was advised to present to the emergency department of this hospital for further evaluation and treatment.
In the emergency department, the patient reported no history of orthopnea or leg swelling, although his weight had increased by 2.2 kg during the past year. He reported eating and drinking normally, with no nausea, vomiting, or diarrhea. He had no weakness, loss of sensation, headache, or vision changes. Other medical history was notable for hypertension and hyperlipidemia. Medications included lisinopril, hydrochlorothiazide, and atorvastatin; there were no known allergies to medications. He had smoked tobacco in the past but had quit 40 years earlier; he drank alcohol rarely and did not use illicit drugs. He was a retired teacher and lived with his wife in New England. His family history included heart disease in his father and pancreatic cancer in his mother.
The temperature was 36.8[degrees]C, the blood pressure 156/76 mm Hg, the pulse 56 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 74.8 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.4. The physical examination was normal.
The blood sodium level was 123 mmol per liter (reference range, 135 to 145); other laboratory test results are shown in Table 1. The patient received 250 ml of intravenous isotonic fluids. Four hours later, the blood sodium level was 127 mmol per liter. The patient was instructed to stop taking hydrochlorothiazide and to follow up with his primary care physician; he was discharged from the emergency department.	
Table 1
After the patient returned home, his fatigue diminished. One week later, involuntary movements in the left arm and hand developed. The patient described the movements as spasms that caused the arm to flex at the elbow or wrist. The episodes lasted less than 5 seconds and occurred multiple times per day. They often occurred after position changes or sudden movements and often caused him to drop any object he was holding in his left hand. He described feeling a strange sensation immediately before the movements but being unable to suppress them. The patient's wife had noticed that occasionally during the involuntary movements of the left arm and hand, the left side of the patient's face pulled to the side as though he were grimacing. The episodes increased in frequency during the next 2 weeks, and 3 weeks after discharge from the emergency department, the patient returned to this hospital for additional evaluation.
On evaluation, the patellar reflexes were 3+; the remainder of the physical examination was normal. The blood sodium level was 123 mmol per liter. Other laboratory test results are shown in Table 1. Blood levels of thyrotropin and N-terminal pro-B-type natriuretic peptide were normal. The blood cortisol level was 13.5 [mu]g per deciliter; 30 minutes after the administration of 250 [mu]g of cosyntropin, the blood cortisol level was 27.9 [mu]g per deciliter. The patient received 1 liter of intravenous isotonic fluids. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed mild, scattered, nonspecific hypoattenuation of the periventricular and subcortical white matter bilaterally. The patient was admitted to the hospital for further evaluation.
Ten hours later, the blood sodium level was 121 mmol per liter. The patient was asked to limit his intake of water to less than 1 liter per day, and sodium chloride tablets were administered. Twelve hours later, the blood sodium level was 123 mmol per liter. A single, unwitnessed episode of involuntary movement of the left arm and left side of the face occurred.
On the second and third hospital days, intravenous desmopressin and hypertonic fluids were administered, and the blood sodium level gradually increased to 132 mmol per liter. Additional imaging studies were obtained. Magnetic resonance imaging of the head was performed before and after the administration of intravenous contrast material; T2-weighted, fluid-attenuated inversion recovery images showed mild, scattered hyperintensities in the periventricular and subcortical white matter. CT of the chest, abdomen, and pelvis was performed after the administration of intravenous contrast material; the scan showed a small cluster of nodules and linear opacities in the right middle lobe and multilevel degenerative changes of the lumbar spine and bilateral hip joints.
On the fourth hospital day, the administration of intravenous hypertonic fluids and desmopressin was stopped, oral furosemide was added, and sodium chloride tablets were continued. Over the next 3 days, the blood sodium level increased to 137 mmol per liter. The patient was discharged home on the seventh hospital day having had no additional episodes of involuntary movements.
The blood sodium level was normal 2 days after discharge and again 8 days after discharge. The patient was instructed to drink water when he was thirsty without limiting his daily intake. Two weeks after discharge, the patient noticed recurrence of the involuntary movements of the left arm and left side of the face. He was evaluated by his primary care physician. The physical examination was normal, and no involuntary movements were observed. The blood sodium level was 134 mmol per liter. The patient was instructed to limit his intake of water to 2 liters per day.
Four weeks after discharge, the patient was evaluated in the nephrology clinic of this hospital. He reported that the involuntary movements of the left arm and left side of the face had increased in frequency, occurring once per hour. The blood sodium level was 134 mmol per liter. He was referred to the neurology clinic of this hospital for further evaluation. At the neurology clinic, a diagnostic test was performed, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Hemichorea\u2013hemiballismus syndrome secondary to nonketotic hyperglycemia. The patient's involuntary movements of the left arm and face, described as spasms, are consistent with hemichorea\u2013hemiballismus, a movement disorder characterized by continuous, involuntary, irregular, jerking, and/or flinging movements. The patient's history of hyperglycemia and the absence of ketosis suggest nonketotic hyperglycemia as the underlying cause. The patient's hyponatremia could be a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is often associated with nonketotic hyperglycemia. The patient's improvement with correction of his hyponatremia further supports this diagnosis.""
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        ""role"": ""assistant"",
        ""content"": ""Hemichorea\u2013hemiballismus syndrome secondary to hyponatremia. The patient's involuntary movements of the left arm and face, described as spasms, are consistent with hemichorea\u2013hemiballismus, a movement disorder characterized by involuntary, irregular, jerking (chorea) or flinging (ballismus) movements on one side of the body. The patient's hyponatremia, or low sodium levels, is a known cause of this syndrome. The patient's movements improved with correction of his sodium levels, further supporting this diagnosis.""
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}",Hemichorea and hemiballismus due to hyponatremia,N,"{
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        ""content"": ""The patient is a 79-year-old man presenting with hyponatremia and involuntary movements of the arm and face. The differential diagnosis for this patient includes Parkinson's disease, Huntington's disease, essential tremor, and hemifacial spasm. Parkinson's disease is less likely because the patient's symptoms are not accompanied by rigidity, bradykinesia, or postural instability. Huntington's disease is also less likely because the patient does not have a family history of the disease and his symptoms are not accompanied by cognitive decline or psychiatric symptoms. Essential tremor is less likely because the patient's symptoms are not bilateral and do not improve with alcohol consumption. Hemifacial spasm is less likely because the patient's symptoms are not limited to the face. The patient's symptoms are consistent with hemiballismus, a rare movement disorder characterized by involuntary, irregular, large-amplitude, and violent flinging movements of the limbs on one side of the body. Hemiballismus is usually caused by a lesion in the subthalamic nucleus, often due to a stroke, but can also be caused by nonketotic hyperglycemia, which can cause hyponatremia. The patient's hyponatremia, which has been resistant to treatment, and the absence of other causes of hemiballismus on imaging studies, suggest that his hemiballismus is due to nonketotic hyperglycemia.\n\nDiagnosis: Hemiballismus due to nonketotic hyperglycemia.""
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}",Hemiballismus due to nonketotic hyperglycemia,N
10.1056/NEJMcpc1909623,Case 14-2020: A 37-Year-Old Man with Joint Pain and Eye Redness,"Hematocrit (%)   37.2
Hemoglobin (g/dl)   13.2
White-cell count (per μl)   9400
Differential count (%)
Neutrophils   70
Lymphocytes   23
Monocytes   5
Eosinophils   2
Basophils   0
Platelet count (per μl)   211,000
Red-cell count (per μl) 4,000,000–5,900,000 3,970,000
Mean corpuscular volume (fl)   94
Red-cell distribution width (%)   13
Alkaline phosphatase (U/liter)   70
Bilirubin (mg/dl)
Total 0–1.0 1.1
Direct   0.2
Alanine aminotransferase (U/liter)   33
Aspartate aminotransferase (U/liter)   67
Albumin (g/dl)   3.7
Total protein (g/dl) 6. .3 7.1
Globulin (g/dl)   3.4
Prothrombin time (sec)   14.8
International normalized ratio   1.3
Creatine kinase (U/liter)   2199
Erythrocyte sedimentation rate (mm/hr)   63
C-reactive protein (mg/liter)   69.3","Proteinase 3 antineutrophil cytoplasmic antibody–
associated vasculitis consistent with granulomatosis with polyangiitis.",Granulomatosis with polyangiitis associated with antineutrophil cytoplasmic antibody directed against proteinase 3.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 37-year-old man was evaluated in the rheumatology clinic of this hospital for joint pain and rash.
The patient had been well until 2 years before this evaluation, when intermittent arthralgias developed in the joints of the hands. Four months before presentation, the pain in the hands became more severe, and new joint pain developed in the wrists, knees, ankles, and shoulders. He had occasional joint stiffness, most commonly in the morning. The patient was evaluated by his primary care physician. The blood levels of electrolytes were reportedly normal, as were the results of kidney-function tests, the complete blood count, and the erythrocyte sedimentation rate. A screening test for Lyme disease was reportedly negative. Despite the use of nonsteroidal antiinflammatory drugs, the joint arthralgias did not abate, and the patient was referred to the rheumatology clinic of this hospital for further evaluation.
In the rheumatology clinic, the patient reported the new development of a rash on his hands and feet, as well as pain in his calves that worsened after prolonged standing. He had no fever, chills, night sweats, weakness, chest pain, or shortness of breath. On examination, several small, nonblanching, petechial lesions were noted on the hands and feet, and four slightly raised, erythematous lesions were seen on the hands and left lower leg. He had tenderness in the wrists, metacarpophalangeal joints, ankles, and metatarsophalangeal joints, as well as pain with motion of the hips and knees. The muscles of the calves were firm and tender on palpation. The remainder of the physical examination was unremarkable. The complete blood count and differential count were normal. Blood tests for rheumatoid factor and anti-cyclic citrullinated peptide antibodies were negative. The erythrocyte sedimentation rate was 77 mm per hour (reference range, 0 to 11), and the C-reactive protein level was 58 mg per liter (reference value,  ). Blood tests were positive for antinuclear antibodies at titers of 1:40 and 1:160, with a speckled pattern. Hydroxychloroquine and prednisone were prescribed. However, during the next week, the patient had difficulty walking owing to progressively worsening calf pain, and he presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported dry mouth and weight loss of 9 kg over a period of 2 months that he attributed to changes in diet and exercise. Two days before presentation, he had noted redness and mild pain in both eyes but no blurred vision. Five days before presentation, his temperature measured at home had been 37.9[degrees]C. His medical history included irritable bowel syndrome, obesity, and gastroesophageal reflux disease, which had resulted in a stricture that required balloon dilation of the distal esophagus. Twenty-two months before this presentation, mild elevations in alanine aminotransferase and aspartate aminotransferase levels detected during routine laboratory testing had been attributed to nonalcoholic steatohepatitis. He had had multiple previous tick bites and had been treated empirically with doxycycline in the past, most recently 14 months before presentation. Medications were hydroxychloroquine, prednisone, omeprazole, ergocalciferol, alprazolam, a multivitamin, and glucosamine. The patient did not smoke tobacco or use illicit drugs; he drank alcohol occasionally. He was married with two children and lived in a suburb of Boston. He worked as an executive in a local firm. There was no family history of autoimmune disease, including rheumatoid arthritis or systemic lupus erythematosus.
On examination, the temperature was 36.3[degrees]C, the blood pressure 146/88 mm Hg, the pulse 89 beats per minute, and the oxygen saturation 99% while the patient was breathing ambient air. Diffuse conjunctival injection affecting the episcleral vessels was present in both eyes, and a violaceous hue was noted in the underlying sclera (Figure 1A). The patient was able to stand from a seated position without the use of his hands, but ambulation was difficult because of pain in the calves. The calves appeared swollen, without erythema or warmth, and were firm and tender on palpation. There was pain on flexion and extension of the right great toe, with no erythema, warmth, or swelling of the joints. Erythematous papules were present on the left wrist, the left olecranon (Figure 1B), and the right olecranon. Several erythematous lesions were noted on the left lower leg and right foot (Figure 1C and 1D) and on the hands; they were not raised and did not blanch with pressure. The remainder of the physical examination was normal. Blood levels of electrolytes were normal, as were the results of renal-function tests. Urinalysis revealed 2+ blood (reference value, negative), 1+ protein (reference value, negative), 50 to 100 red cells per high-power field (reference range, 0 to 2), and 5 to 10 white cells per high-power field (reference range, 0 to 2). Examination of the urine sediment revealed dysmorphic red cells and red-cell casts that were too numerous to count. Blood tests for anti-double-stranded DNA antibody, anti-Ro antibody, and anti-La antibody were negative; other laboratory test results are shown in Table 1. Imaging studies of the left leg were obtained.	
Figure 1 
Dr. Ambrose J. Huang: Magnetic resonance imaging (MRI) of the left lower leg (Figure 2), performed before and after the administration of intravenous gadolinium-based contrast material, revealed nonspecific, diffuse muscle edema, which was most prominent in the posterior compartment of the calf, with mild associated contrast enhancement. There was no evidence of muscle atrophy, myonecrosis, bony involvement, or drainable fluid collections.	
Figure 2
Dr. Stone: The patient was admitted to the hospital, and a diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 37-year-old man was evaluated in the rheumatology clinic of this hospital for joint pain and rash.
The patient had been well until 2 years before this evaluation, when intermittent arthralgias developed in the joints of the hands. Four months before presentation, the pain in the hands became more severe, and new joint pain developed in the wrists, knees, ankles, and shoulders. He had occasional joint stiffness, most commonly in the morning. The patient was evaluated by his primary care physician. The blood levels of electrolytes were reportedly normal, as were the results of kidney-function tests, the complete blood count, and the erythrocyte sedimentation rate. A screening test for Lyme disease was reportedly negative. Despite the use of nonsteroidal antiinflammatory drugs, the joint arthralgias did not abate, and the patient was referred to the rheumatology clinic of this hospital for further evaluation.
In the rheumatology clinic, the patient reported the new development of a rash on his hands and feet, as well as pain in his calves that worsened after prolonged standing. He had no fever, chills, night sweats, weakness, chest pain, or shortness of breath. On examination, several small, nonblanching, petechial lesions were noted on the hands and feet, and four slightly raised, erythematous lesions were seen on the hands and left lower leg. He had tenderness in the wrists, metacarpophalangeal joints, ankles, and metatarsophalangeal joints, as well as pain with motion of the hips and knees. The muscles of the calves were firm and tender on palpation. The remainder of the physical examination was unremarkable. The complete blood count and differential count were normal. Blood tests for rheumatoid factor and anti-cyclic citrullinated peptide antibodies were negative. The erythrocyte sedimentation rate was 77 mm per hour (reference range, 0 to 11), and the C-reactive protein level was 58 mg per liter (reference value,  ). Blood tests were positive for antinuclear antibodies at titers of 1:40 and 1:160, with a speckled pattern. Hydroxychloroquine and prednisone were prescribed. However, during the next week, the patient had difficulty walking owing to progressively worsening calf pain, and he presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported dry mouth and weight loss of 9 kg over a period of 2 months that he attributed to changes in diet and exercise. Two days before presentation, he had noted redness and mild pain in both eyes but no blurred vision. Five days before presentation, his temperature measured at home had been 37.9[degrees]C. His medical history included irritable bowel syndrome, obesity, and gastroesophageal reflux disease, which had resulted in a stricture that required balloon dilation of the distal esophagus. Twenty-two months before this presentation, mild elevations in alanine aminotransferase and aspartate aminotransferase levels detected during routine laboratory testing had been attributed to nonalcoholic steatohepatitis. He had had multiple previous tick bites and had been treated empirically with doxycycline in the past, most recently 14 months before presentation. Medications were hydroxychloroquine, prednisone, omeprazole, ergocalciferol, alprazolam, a multivitamin, and glucosamine. The patient did not smoke tobacco or use illicit drugs; he drank alcohol occasionally. He was married with two children and lived in a suburb of Boston. He worked as an executive in a local firm. There was no family history of autoimmune disease, including rheumatoid arthritis or systemic lupus erythematosus.
On examination, the temperature was 36.3[degrees]C, the blood pressure 146/88 mm Hg, the pulse 89 beats per minute, and the oxygen saturation 99% while the patient was breathing ambient air. Diffuse conjunctival injection affecting the episcleral vessels was present in both eyes, and a violaceous hue was noted in the underlying sclera (Figure 1A). The patient was able to stand from a seated position without the use of his hands, but ambulation was difficult because of pain in the calves. The calves appeared swollen, without erythema or warmth, and were firm and tender on palpation. There was pain on flexion and extension of the right great toe, with no erythema, warmth, or swelling of the joints. Erythematous papules were present on the left wrist, the left olecranon (Figure 1B), and the right olecranon. Several erythematous lesions were noted on the left lower leg and right foot (Figure 1C and 1D) and on the hands; they were not raised and did not blanch with pressure. The remainder of the physical examination was normal. Blood levels of electrolytes were normal, as were the results of renal-function tests. Urinalysis revealed 2+ blood (reference value, negative), 1+ protein (reference value, negative), 50 to 100 red cells per high-power field (reference range, 0 to 2), and 5 to 10 white cells per high-power field (reference range, 0 to 2). Examination of the urine sediment revealed dysmorphic red cells and red-cell casts that were too numerous to count. Blood tests for anti-double-stranded DNA antibody, anti-Ro antibody, and anti-La antibody were negative; other laboratory test results are shown in Table 1. Imaging studies of the left leg were obtained.	
Figure 1 
Dr. Ambrose J. Huang: Magnetic resonance imaging (MRI) of the left lower leg (Figure 2), performed before and after the administration of intravenous gadolinium-based contrast material, revealed nonspecific, diffuse muscle edema, which was most prominent in the posterior compartment of the calf, with mild associated contrast enhancement. There was no evidence of muscle atrophy, myonecrosis, bony involvement, or drainable fluid collections.	
Figure 2
Dr. Stone: The patient was admitted to the hospital, and a diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of joint pain, rash, dry mouth, weight loss, and redness and pain in the eyes, along with the laboratory findings of elevated erythrocyte sedimentation rate, C-reactive protein level, and positive antinuclear antibodies, suggest an autoimmune disease. The presence of dysmorphic red cells and red-cell casts in the urine indicate kidney involvement, which is common in systemic lupus erythematosus (SLE). However, the patient tested negative for anti-double-stranded DNA antibody, anti-Ro antibody, and anti-La antibody, which are typically present in SLE. The patient's symptoms of calf pain and difficulty walking, along with the MRI findings of muscle edema, suggest muscle inflammation or myositis, which can occur in autoimmune diseases such as dermatomyositis or polymyositis. The presence of erythematous papules on the patient's joints and erythematous lesions on the skin that do not blanch with pressure are characteristic of Gottron's papules and Gottron's sign, respectively, which are specific for dermatomyositis. Therefore, the patient's symptoms, physical examination findings, and laboratory results are most consistent with dermatomyositis.\n\nDiagnosis: Dermatomyositis.""
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        ""content"": ""The patient's symptoms of joint pain, rash, dry mouth, weight loss, and eye redness, along with the laboratory findings of elevated erythrocyte sedimentation rate, C-reactive protein level, and antinuclear antibodies, suggest an autoimmune process. The presence of dysmorphic red cells and red-cell casts in the urine indicates glomerulonephritis, which is often associated with systemic autoimmune diseases. The negative tests for rheumatoid factor, anti-cyclic citrullinated peptide antibodies, anti-double-stranded DNA antibody, anti-Ro antibody, and anti-La antibody rule out rheumatoid arthritis and systemic lupus erythematosus. The MRI findings of muscle edema in the calf are consistent with myositis, another feature of systemic autoimmune diseases. Taken together, these findings suggest a diagnosis of a systemic vasculitis, specifically polyarteritis nodosa, which can cause a wide range of symptoms including those seen in this patient. \n\nDiagnosis: Polyarteritis nodosa.""
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}",Polyarteritis nodosa,N,"{
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        ""content"": ""The patient is a 37-year-old man presenting with joint pain, rash, calf pain, dry mouth, weight loss, and redness in both eyes. The differential diagnosis for this patient includes rheumatoid arthritis, systemic lupus erythematosus, Lyme disease, and vasculitis. The patient's blood tests were negative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies, making rheumatoid arthritis less likely. The patient's blood tests were also negative for anti-double-stranded DNA antibody, anti-Ro antibody, and anti-La antibody, making systemic lupus erythematosus less likely. The patient's screening test for Lyme disease was reportedly negative, making Lyme disease less likely. The patient's symptoms of joint pain, rash, calf pain, dry mouth, weight loss, and redness in both eyes, along with his elevated erythrocyte sedimentation rate and C-reactive protein level, are consistent with vasculitis. The patient's urinalysis revealed blood and protein in the urine, as well as dysmorphic red cells and red-cell casts, which are indicative of glomerulonephritis, a common feature of vasculitis. The patient's MRI of the left lower leg revealed nonspecific, diffuse muscle edema, which is also consistent with vasculitis. \n\nDiagnosis: Vasculitis""
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}",Vasculitis,N
10.1056/NEJMcpc1916254,"Case 13-2020: A 29-Year-Old Man with High Blood Pressure, Renal Insufficiency, and Hematuria","Hemoglobin (g/dl)   10.7
Hematocrit (%)   31.5
Red-cell count (per μl) 
3,660,000
Mean corpuscular volume (fl)   86.1
White-cell count (per μl)   7670
Platelet count (per μl)   214,000
Sodium (mmol/liter)   140
Potassium (mmol/liter)   3.9
Chloride (mmol/liter)   99
Carbon dioxide (mmol/liter)   20
Urea nitrogen (mg/dl)   48
Creatinine (mg/dl)   3.93
Glucose (mg/dl)   80
Calcium (mg/dl)   9.6
Albumin (g/dl)   3.8
Cholesterol (mg/dl)
Total <200 171
Low-density lipoprotein   110
High-density lipoprotein   54
Triglycerides (mg/dl)   34
Phosphorus (mg/dl)   4.4
25-Hydroxyvitamin D (ng/dl) 2 0 10
Parathyroid hormone (pg/ml)   62
Kappa light chain (mg/dl)   106.8
Lambda light chain (mg/dl)   70.0
IgG (mg/dl)   687
IgA (mg/dl)   513
IgM (mg/dl)   46
Serum protein electrophoresis No M component No M component        Urinary Laboratory Data.                                                                                   Color Yellow Yellow
Clarity Clear Slightly cloudy
pH   5.0
Specific gravity   1.012
Glucose Negative Negative
Leukocyte esterase Negative Negative
Nitrite Negative Negative
Blood Negative 3+
Protein Negative 3+
Erythrocytes (per high‚Äëpower field)    
Leukocytes (per high‑power field)   3–5
Bacteria None 1+
Creatinine (mg/dl) 98
Total protein (mg/dl) 0. .5 556.3",Crescentic IgA nephropathy,gA nephropathy or C3 glomerulopathy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-year-old white man was evaluated at the nephrology clinic of this hospital because of hypertension, renal insufficiency, and hematuria.
Eight months before the current evaluation, at a physical examination performed for employment, the patient was told he had high blood pressure; no further evaluation was performed. One month before the current evaluation, he was seen by his primary care physician at another institution for a routine physical examination. A review of systems was reportedly negative. The temperature was 36.3[degrees]C, the heart rate 67 beats per minute, the blood pressure 175/100 mm Hg, and the oxygen saturation 99% while he was breathing ambient air. Examination of the skin revealed a rash consistent with rosacea and a small cyst on the back; the remainder of the examination was normal. The blood level of hemoglobin was 10.7 g per deciliter (normal range, 14.0 to 18.0), hematocrit 31.5% (normal range, 40.0 to 54.0), urea nitrogen 37 mg per deciliter (13.2 mmol per liter; normal range, 9 to 20 mg per deciliter [3.2 to 7.1 mmol per liter]), creatinine 3.1 mg per deciliter (274 [mu]mol per liter; normal range, 0.7 to 1.3 mg per deciliter [62 to 115 [mu]mol per liter]), potassium 4.5 mmol per liter (normal range, 3.5 to 5.1), albumin 3.7 g per deciliter (normal range, 3.3 to 5.0), and glucose 86 mg per deciliter (4.8 mmol per liter; normal range, 70 to 99 mg per deciliter [3.9 to 5.5 mmol per liter]). A screening test for human immunodeficiency virus types 1 and 2 was negative. Amlodipine therapy was started.
Six days later, dark urine developed. After 4 days, the patient was evaluated by his primary care physician. He reported no dysuria, urinary frequency, obstructive urinary symptoms, antecedent trauma, or vigorous exercise. Examination was notable for a blood pressure of 148/100 mm Hg. The blood level of urea nitrogen was 46 mg per deciliter (16.4 mmol per liter), creatinine 3.5 mg per deciliter (309 [mu]mol per liter), and potassium 5.7 mmol per liter. Other laboratory test results were essentially unchanged from 10 days earlier. A urinalysis was notable for yellow, cloudy urine, with 3+ blood (normal value, negative), 3+ protein (normal value, negative), 0 to 5 erythrocytes per high-power field (normal range, <5), and 10 to 20 leukocytes per high-power field (normal range, <2). Urine was obtained for culture. The dose of amlodipine was increased. The patient was referred to the outpatient nephrology clinic of this hospital.
At this hospital, the patient reported that he had had intermittent hematuria and episodic foamy urine during the previous 10 months. He had new pedal edema that was greater on the right side than on the left side. Since the last visit with his primary care physician approximately 2 weeks earlier, he had had 2 days of coryza but no other respiratory symptoms. There was no anorexia, weight change, pruritus, abdominal pain, change in bowel habits, chest pain, dyspnea, wheezing, cough, hemoptysis, visual or auditory disturbances, headache, neurologic symptoms, or other bleeding symptoms. The medical history was notable for rosacea and childhood asthma. Medications included amlodipine. There were no known adverse reactions to medications.
The patient was in a long-term monogamous relationship. He worked in maintenance but had not been exposed to inhaled chemicals or environmental allergens. He had not traveled outside Massachusetts. He drank three beers per week and had last smoked marijuana 10 years earlier; he had never used tobacco or other illicit drugs. There was a history of systemic hypertension in his paternal grandfather and a paternal aunt, as well as a history of cancer in multiple maternal relatives, including his mother, who had had brain cancer, and his maternal grandmother and a maternal aunt, who had had breast cancer. There was no known family history of kidney disease.
The temperature was 36.9[degrees]C, the heart rate 71 beats per minute, and the blood pressure 160/102 mm Hg. The weight was 89 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 27.2. There was 1+ pedal edema. The remainder of the examination was normal.
Results of liver-function tests, blood levels of creatine kinase and glycated hemoglobin, the international normalized ratio, and the prothrombin time were normal; other laboratory test results are shown in Table 1 and Table 2. Tests for hepatitis B surface antigens and surface antibodies, hepatitis C antibodies, antinuclear antibodies, and anti-double-stranded DNA antibodies were negative. Examination of urine sediment revealed fine granular casts, dysmorphic red cells, and rare white-cell casts.	
Table 1 
Dr. Amirkasra Mojtahed: On renal ultrasonography, the kidneys were normal in size. There was increased bilateral renal parenchymal echogenicity and no evidence of hydronephrosis (Figure 1).	
Figure 1 
Dr. Kalim: Amlodipine was stopped, and labetalol was started. Diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-year-old white man was evaluated at the nephrology clinic of this hospital because of hypertension, renal insufficiency, and hematuria.
Eight months before the current evaluation, at a physical examination performed for employment, the patient was told he had high blood pressure; no further evaluation was performed. One month before the current evaluation, he was seen by his primary care physician at another institution for a routine physical examination. A review of systems was reportedly negative. The temperature was 36.3[degrees]C, the heart rate 67 beats per minute, the blood pressure 175/100 mm Hg, and the oxygen saturation 99% while he was breathing ambient air. Examination of the skin revealed a rash consistent with rosacea and a small cyst on the back; the remainder of the examination was normal. The blood level of hemoglobin was 10.7 g per deciliter (normal range, 14.0 to 18.0), hematocrit 31.5% (normal range, 40.0 to 54.0), urea nitrogen 37 mg per deciliter (13.2 mmol per liter; normal range, 9 to 20 mg per deciliter [3.2 to 7.1 mmol per liter]), creatinine 3.1 mg per deciliter (274 [mu]mol per liter; normal range, 0.7 to 1.3 mg per deciliter [62 to 115 [mu]mol per liter]), potassium 4.5 mmol per liter (normal range, 3.5 to 5.1), albumin 3.7 g per deciliter (normal range, 3.3 to 5.0), and glucose 86 mg per deciliter (4.8 mmol per liter; normal range, 70 to 99 mg per deciliter [3.9 to 5.5 mmol per liter]). A screening test for human immunodeficiency virus types 1 and 2 was negative. Amlodipine therapy was started.
Six days later, dark urine developed. After 4 days, the patient was evaluated by his primary care physician. He reported no dysuria, urinary frequency, obstructive urinary symptoms, antecedent trauma, or vigorous exercise. Examination was notable for a blood pressure of 148/100 mm Hg. The blood level of urea nitrogen was 46 mg per deciliter (16.4 mmol per liter), creatinine 3.5 mg per deciliter (309 [mu]mol per liter), and potassium 5.7 mmol per liter. Other laboratory test results were essentially unchanged from 10 days earlier. A urinalysis was notable for yellow, cloudy urine, with 3+ blood (normal value, negative), 3+ protein (normal value, negative), 0 to 5 erythrocytes per high-power field (normal range, <5), and 10 to 20 leukocytes per high-power field (normal range, <2). Urine was obtained for culture. The dose of amlodipine was increased. The patient was referred to the outpatient nephrology clinic of this hospital.
At this hospital, the patient reported that he had had intermittent hematuria and episodic foamy urine during the previous 10 months. He had new pedal edema that was greater on the right side than on the left side. Since the last visit with his primary care physician approximately 2 weeks earlier, he had had 2 days of coryza but no other respiratory symptoms. There was no anorexia, weight change, pruritus, abdominal pain, change in bowel habits, chest pain, dyspnea, wheezing, cough, hemoptysis, visual or auditory disturbances, headache, neurologic symptoms, or other bleeding symptoms. The medical history was notable for rosacea and childhood asthma. Medications included amlodipine. There were no known adverse reactions to medications.
The patient was in a long-term monogamous relationship. He worked in maintenance but had not been exposed to inhaled chemicals or environmental allergens. He had not traveled outside Massachusetts. He drank three beers per week and had last smoked marijuana 10 years earlier; he had never used tobacco or other illicit drugs. There was a history of systemic hypertension in his paternal grandfather and a paternal aunt, as well as a history of cancer in multiple maternal relatives, including his mother, who had had brain cancer, and his maternal grandmother and a maternal aunt, who had had breast cancer. There was no known family history of kidney disease.
The temperature was 36.9[degrees]C, the heart rate 71 beats per minute, and the blood pressure 160/102 mm Hg. The weight was 89 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 27.2. There was 1+ pedal edema. The remainder of the examination was normal.
Results of liver-function tests, blood levels of creatine kinase and glycated hemoglobin, the international normalized ratio, and the prothrombin time were normal; other laboratory test results are shown in Table 1 and Table 2. Tests for hepatitis B surface antigens and surface antibodies, hepatitis C antibodies, antinuclear antibodies, and anti-double-stranded DNA antibodies were negative. Examination of urine sediment revealed fine granular casts, dysmorphic red cells, and rare white-cell casts.	
Table 1 
Dr. Amirkasra Mojtahed: On renal ultrasonography, the kidneys were normal in size. There was increased bilateral renal parenchymal echogenicity and no evidence of hydronephrosis (Figure 1).	
Figure 1 
Dr. Kalim: Amlodipine was stopped, and labetalol was started. Diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with hypertension, renal insufficiency, and hematuria. The patient's blood work shows elevated levels of urea nitrogen and creatinine, indicating kidney dysfunction. The patient also has proteinuria and hematuria, further suggesting kidney disease. The patient's renal ultrasonography shows increased bilateral renal parenchymal echogenicity, which is often seen in chronic kidney diseases. The patient's symptoms and lab results are consistent with glomerulonephritis, a type of kidney disease where the glomeruli, the tiny filters in the kidneys, are damaged. This can cause blood and protein to leak into the urine and can result in kidney damage and renal insufficiency. \n\nDiagnosis: Glomerulonephritis""
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        ""content"": ""The patient presents with hypertension, renal insufficiency, and hematuria. The patient also has proteinuria and dysmorphic red cells in the urine, which are indicative of glomerular disease. The patient's renal ultrasound shows increased bilateral renal parenchymal echogenicity, which is often seen in chronic kidney disease. The patient's history of hypertension and the absence of other symptoms such as fever, rash, or joint pain make an autoimmune or infectious cause of glomerulonephritis less likely. The patient's renal insufficiency is also chronic, as indicated by anemia and increased creatinine levels. Therefore, the most likely diagnosis is hypertensive nephrosclerosis, a common cause of chronic kidney disease.\n\nDiagnosis: Hypertensive Nephrosclerosis""
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        ""content"": ""The patient is a 29-year-old man presenting with hypertension, renal insufficiency, and hematuria. The differential diagnosis for this patient includes glomerulonephritis, polycystic kidney disease, renal artery stenosis, and nephrotic syndrome. The patient's renal ultrasound showed increased bilateral renal parenchymal echogenicity but no evidence of hydronephrosis or cysts, making polycystic kidney disease less likely. The absence of abdominal bruit and the patient's young age make renal artery stenosis less likely. The patient's urinalysis showed proteinuria and hematuria, which are consistent with glomerulonephritis or nephrotic syndrome. However, the presence of dysmorphic red cells and white-cell casts in the urine sediment is more suggestive of glomerulonephritis. Furthermore, the patient's hypertension and renal insufficiency are also consistent with glomerulonephritis. \n\nDiagnosis: Glomerulonephritis.""
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10.1056/NEJMcpc1916256,"Case 12-2020: A 24-Year-Old Man with Fever, Cough, and Dyspnea","White-cell count (per μl)   16,040
Differential count (per μl)
Neutrophils   12,350
Lymphocytes   1120
Eosinophils   160
Metamyelocytes 0 1604
Hemoglobin (g/dl)   16.5
Hematocrit (%)   47.4
Platelet count (per μl)   73,000
Prothrombin time (sec)   14.2
Prothrombin-time international normalized ratio   1.1
Activated partial-thromboplastin time (sec)  6.0 36.9
d-dimer (ng/ml)   2243
Fibrinogen (mg/dl) 15 0 341
Sodium (mmol/liter)   136
Potassium (mmol/liter)   5.4
Chloride (mmol/liter)   104
Carbon dioxide (mmol/liter)   20
Anion gap (mmol/liter)   12
Urea nitrogen (mg/dl)   14
Creatinine (mg/dl)   0.92
Glucose (mg/dl)   142
Calcium (mg/dl)   7.4
Magnesium (mg/dl)   1.8
Phosphorus (mg/dl)   2.4
Protein (g/dl)
Total 6. .3 5.2
Albumin   2.3
Globulin   2.9
Alanine aminotransferase (U/liter)   23
Aspartate aminotransferase (U/liter)   42
Alkaline phosphatase (U/liter)   32
Lactic acid (mmol/liter)   3.3
Lactate dehydrogenase (U/liter)  656
Haptoglobin (mg/dl)  208
C-reactive protein (mg/liter)   43.7
Erythrocyte sedimentation rate (mm/hr)   5",Hantavirus cardiopulmonary syndrome,Hantavirus cardiopulmonary syndrome,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 24-year-old man was transferred to this hospital because of fever, fatigue, cough, and dyspnea.
The patient had been well until 5 days before this presentation, when fatigue, malaise, fever, chills, and cough that was productive of terra cotta-colored sputum developed. Three days before this presentation, he had presented to an urgent care clinic with nausea, vomiting, decreased appetite, and diarrhea. A chest radiograph was reportedly normal, and the patient was told he had a viral illness. Intravenous fluids were administered, and he was advised to return to the clinic if symptoms persisted or worsened.
The next day, symptoms increased in severity, and the patient was unable to eat or drink owing to persistent nausea and vomiting. Back pain, neck pain, headache, and photophobia developed. The patient reported positional chest pain and dyspnea, which progressed rapidly, such that he could not walk up a flight of stairs. The day before presentation to this hospital, he presented to another hospital.
The temperature was 36.5[degrees]C, the blood pressure 105/66 mm Hg, the heart rate 73 beats per minute, the respiratory rate 35 breaths per minute, and the oxygen saturation 88% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. On examination, he appeared unwell and in mild distress. Breath sounds were decreased throughout the upper and lower lung fields, and scattered expiratory wheezes were present. The white-cell count was 21,890 per microliter (reference range, 4800 to 10,800), with a neutrophil count of 45% (9851 per microliter; reference range, 37 to 80% [1800 to 7700 per microliter]) and a band count of 23% (5035 per microliter; reference range, <5% [0 to 1100 per microliter]). The platelet count was 60,000 per microliter (reference range, 150,000 to 450,000), the creatinine level 1.37 mg per deciliter (121.1 [mu]mol per liter; reference range, 0.66 to 1.25 mg per deciliter [58.3 to 110.5 [mu]mol per liter]), and the lactate level 3.50 mmol per liter (32 mg per deciliter; reference range, 0.70 to 2.10 mmol per liter [6.3 to 18.9 mg per deciliter]). Nucleic acid testing of a nasopharyngeal swab for influenza A and B viruses and respiratory syncytial virus was negative, as was a blood test for heterophile antibodies. Chest radiography revealed diffuse reticulonodular interstitial opacities in both lungs. Vancomycin, ceftriaxone, doxycycline, methylprednisolone, and intravenous fluids were administered.
During the next 3 hours, the oxygen saturation decreased to 80% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 6 liters per minute. Bilevel positive airway pressure was initiated.
Dr. Shaunagh McDermott: Computed tomography (CT) of the chest (Figure 1A through 1C) revealed ground-glass opacities in both lungs and interlobular septal thickening. Small bilateral pleural effusions were also present.	
Figure 1 
Dr. Guell: The patient's family requested that the patient be transferred to this hospital. The patient's trachea was intubated in a nonemergency setting; continuous infusions of norepinephrine, propofol, and hydromorphone were started. He was transported by medical helicopter to this hospital, arriving approximately 17 hours after his presentation to the first hospital.
On the patient's arrival at this hospital, additional history was obtained from family members. The patient had been camping in a northern New England forest for 9 days before presentation to the other hospital. Four days before presentation to this hospital, he found an unattached tick on his head, but he had no known tick bites; however, he had many mosquito bites. The patient lived on the mid-Atlantic coast with two cats in a trailer in which mold was reportedly present. He enjoyed outdoor activities such as dirt biking, hiking, boating, rafting, and swimming in fresh water. He worked in carpentry. During a house renovation project approximately 2 weeks before this presentation, he was bitten by a mouse; he did not seek medical attention.
The patient had a history of chronic lower back pain. He took no medications and had no known drug allergies. He had smoked cigarettes for 13 years and had quit 1 year earlier. During the past year, the patient used electronic cigarettes (e-cigarettes) and smoked commercial marijuana on a daily basis. His parents and older sibling were alive and well; his grandfather was living with a gastrointestinal cancer.
The temperature was 36.3[degrees]C, the blood pressure 98/57 mm Hg, the heart rate 78 beats per minute, and the oxygen saturation 99% while the patient was receiving oxygen through a mechanical ventilator (positive end-expiratory pressure [PEEP], 12 cm of water; tidal volume, 500 ml; fraction of inspired oxygen [FIO2], 1.0; respiratory rate, 15 breaths per minute). The pupils were symmetric and reactive, the lungs were clear on auscultation, and there were no rashes. The remainder of the physical examination was normal. Tests for Legionella pneumophila serogroup 1 and Streptococcus pneumoniae antigens in the urine were negative, as were tests of a nasopharyngeal swab for adenovirus, metapneumovirus, and parainfluenza virus antigens. Screening for antibodies to human immunodeficiency virus (HIV) types 1 and 2 and HIV type 1 p24 antigen was negative. Urinalysis results were normal. Blood cultures were obtained. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. McDermott: A chest radiograph obtained on arrival at this hospital showed diffuse bilateral opacities, with endotracheal and enteric tubes in an appropriate position (Figure 1D).
Dr. Guell: Transthoracic echocardiography revealed diffuse hypokinesis of the left ventricle and a left ventricular ejection fraction of 45% (reference range, 50 to 75). A lumbar puncture was performed. The cerebrospinal fluid was colorless; the total protein level was 31 mg per deciliter (reference range, 5 to 55), the glucose level 93 mg per deciliter (5.2 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]), and the nucleated-cell count 1 per microliter (reference range, 0 to 5). Gram's staining revealed few mononuclear cells and no neutrophils or organisms.
Dr. Alexandra K. Wong: Flexible bronchoscopy performed on the first hospital day (Figure 2) revealed diffuse erythema and inflammation in the airways, scattered areas of submucosal petechiae and hemorrhage, and scant secretions that were most prominent in the left lung. The bronchoalveolar-lavage fluid was clear and yellow; specimens were obtained for culture. These findings are nonspecific and are often seen with infectious or inflammatory processes, typically accompanied by thrombocytopenia.	
Figure 2
Dr. Guell: Treatment with vancomycin, ceftriaxone, and doxycycline was continued, and gentamicin and furosemide were initiated.
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 24-year-old man was transferred to this hospital because of fever, fatigue, cough, and dyspnea.
The patient had been well until 5 days before this presentation, when fatigue, malaise, fever, chills, and cough that was productive of terra cotta-colored sputum developed. Three days before this presentation, he had presented to an urgent care clinic with nausea, vomiting, decreased appetite, and diarrhea. A chest radiograph was reportedly normal, and the patient was told he had a viral illness. Intravenous fluids were administered, and he was advised to return to the clinic if symptoms persisted or worsened.
The next day, symptoms increased in severity, and the patient was unable to eat or drink owing to persistent nausea and vomiting. Back pain, neck pain, headache, and photophobia developed. The patient reported positional chest pain and dyspnea, which progressed rapidly, such that he could not walk up a flight of stairs. The day before presentation to this hospital, he presented to another hospital.
The temperature was 36.5[degrees]C, the blood pressure 105/66 mm Hg, the heart rate 73 beats per minute, the respiratory rate 35 breaths per minute, and the oxygen saturation 88% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. On examination, he appeared unwell and in mild distress. Breath sounds were decreased throughout the upper and lower lung fields, and scattered expiratory wheezes were present. The white-cell count was 21,890 per microliter (reference range, 4800 to 10,800), with a neutrophil count of 45% (9851 per microliter; reference range, 37 to 80% [1800 to 7700 per microliter]) and a band count of 23% (5035 per microliter; reference range, <5% [0 to 1100 per microliter]). The platelet count was 60,000 per microliter (reference range, 150,000 to 450,000), the creatinine level 1.37 mg per deciliter (121.1 [mu]mol per liter; reference range, 0.66 to 1.25 mg per deciliter [58.3 to 110.5 [mu]mol per liter]), and the lactate level 3.50 mmol per liter (32 mg per deciliter; reference range, 0.70 to 2.10 mmol per liter [6.3 to 18.9 mg per deciliter]). Nucleic acid testing of a nasopharyngeal swab for influenza A and B viruses and respiratory syncytial virus was negative, as was a blood test for heterophile antibodies. Chest radiography revealed diffuse reticulonodular interstitial opacities in both lungs. Vancomycin, ceftriaxone, doxycycline, methylprednisolone, and intravenous fluids were administered.
During the next 3 hours, the oxygen saturation decreased to 80% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 6 liters per minute. Bilevel positive airway pressure was initiated.
Dr. Shaunagh McDermott: Computed tomography (CT) of the chest (Figure 1A through 1C) revealed ground-glass opacities in both lungs and interlobular septal thickening. Small bilateral pleural effusions were also present.	
Figure 1 
Dr. Guell: The patient's family requested that the patient be transferred to this hospital. The patient's trachea was intubated in a nonemergency setting; continuous infusions of norepinephrine, propofol, and hydromorphone were started. He was transported by medical helicopter to this hospital, arriving approximately 17 hours after his presentation to the first hospital.
On the patient's arrival at this hospital, additional history was obtained from family members. The patient had been camping in a northern New England forest for 9 days before presentation to the other hospital. Four days before presentation to this hospital, he found an unattached tick on his head, but he had no known tick bites; however, he had many mosquito bites. The patient lived on the mid-Atlantic coast with two cats in a trailer in which mold was reportedly present. He enjoyed outdoor activities such as dirt biking, hiking, boating, rafting, and swimming in fresh water. He worked in carpentry. During a house renovation project approximately 2 weeks before this presentation, he was bitten by a mouse; he did not seek medical attention.
The patient had a history of chronic lower back pain. He took no medications and had no known drug allergies. He had smoked cigarettes for 13 years and had quit 1 year earlier. During the past year, the patient used electronic cigarettes (e-cigarettes) and smoked commercial marijuana on a daily basis. His parents and older sibling were alive and well; his grandfather was living with a gastrointestinal cancer.
The temperature was 36.3[degrees]C, the blood pressure 98/57 mm Hg, the heart rate 78 beats per minute, and the oxygen saturation 99% while the patient was receiving oxygen through a mechanical ventilator (positive end-expiratory pressure [PEEP], 12 cm of water; tidal volume, 500 ml; fraction of inspired oxygen [FIO2], 1.0; respiratory rate, 15 breaths per minute). The pupils were symmetric and reactive, the lungs were clear on auscultation, and there were no rashes. The remainder of the physical examination was normal. Tests for Legionella pneumophila serogroup 1 and Streptococcus pneumoniae antigens in the urine were negative, as were tests of a nasopharyngeal swab for adenovirus, metapneumovirus, and parainfluenza virus antigens. Screening for antibodies to human immunodeficiency virus (HIV) types 1 and 2 and HIV type 1 p24 antigen was negative. Urinalysis results were normal. Blood cultures were obtained. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. McDermott: A chest radiograph obtained on arrival at this hospital showed diffuse bilateral opacities, with endotracheal and enteric tubes in an appropriate position (Figure 1D).
Dr. Guell: Transthoracic echocardiography revealed diffuse hypokinesis of the left ventricle and a left ventricular ejection fraction of 45% (reference range, 50 to 75). A lumbar puncture was performed. The cerebrospinal fluid was colorless; the total protein level was 31 mg per deciliter (reference range, 5 to 55), the glucose level 93 mg per deciliter (5.2 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]), and the nucleated-cell count 1 per microliter (reference range, 0 to 5). Gram's staining revealed few mononuclear cells and no neutrophils or organisms.
Dr. Alexandra K. Wong: Flexible bronchoscopy performed on the first hospital day (Figure 2) revealed diffuse erythema and inflammation in the airways, scattered areas of submucosal petechiae and hemorrhage, and scant secretions that were most prominent in the left lung. The bronchoalveolar-lavage fluid was clear and yellow; specimens were obtained for culture. These findings are nonspecific and are often seen with infectious or inflammatory processes, typically accompanied by thrombocytopenia.	
Figure 2
Dr. Guell: Treatment with vancomycin, ceftriaxone, and doxycycline was continued, and gentamicin and furosemide were initiated.
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fever, fatigue, cough, and dyspnea, along with the presence of ground-glass opacities in both lungs and interlobular septal thickening on CT scan, suggest a severe respiratory infection. The patient's history of camping in a northern New England forest and finding a tick on his head suggest possible exposure to tick-borne diseases. However, the rapid progression of symptoms and severe respiratory distress are more consistent with a severe pneumonia. The patient's history of daily use of electronic cigarettes and commercial marijuana raises the possibility of a vaping-associated lung injury. The patient's exposure to mold in his living environment could also contribute to a fungal lung infection. However, the patient's recent history of being bitten by a mouse during a house renovation project, along with his symptoms of fever, malaise, and cough productive of terra cotta-colored sputum, are highly suggestive of rat-bite fever, caused by the bacterium Streptobacillus moniliformis. This diagnosis is further supported by the patient's elevated white-cell count and band count, indicating a bacterial infection.\n\nDiagnosis: Rat-bite fever.""
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}",Rat-bite fever,N,"{
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        ""content"": ""The patient is a young man who presents with fever, fatigue, cough, and dyspnea. He also has nausea, vomiting, decreased appetite, and diarrhea. His symptoms started after a camping trip in a northern New England forest. He found an unattached tick on his head and had many mosquito bites. He also had a mouse bite during a house renovation project. His chest radiography revealed diffuse reticulonodular interstitial opacities in both lungs. His white-cell count was high, and his platelet count was low. His creatinine level was slightly elevated, and his lactate level was high. His chest CT revealed ground-glass opacities in both lungs and interlobular septal thickening. Small bilateral pleural effusions were also present. His bronchoscopy revealed diffuse erythema and inflammation in the airways, scattered areas of submucosal petechiae and hemorrhage, and scant secretions that were most prominent in the left lung. The differential diagnosis for this patient includes pneumonia, sepsis, tick-borne diseases, and hantavirus pulmonary syndrome. His symptoms and the fact that he was camping in a forest and had a tick on his head make tick-borne diseases such as Lyme disease, babesiosis, and anaplasmosis possible. However, his symptoms are severe, and he has ground-glass opacities in both lungs, which are not typical for these diseases. His mouse bite and the fact that he was in a forest make hantavirus pulmonary syndrome a possibility. This disease is caused by a virus that is carried by rodents, and it can cause severe respiratory symptoms and a low platelet count, which the patient has. His symptoms started after his camping trip and his mouse bite, which fits with the incubation period of hantavirus pulmonary syndrome. Therefore, hantavirus pulmonary syndrome is the most likely diagnosis.\n\nDiagnosis: Hantavirus pulmonary syndrome.""
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}",Hantavirus pulmonary syndrome,Y
10.1056/NEJMcpc1916252,"Case 11-2020: A 37-Year-Old Man with Facial Droop, Dysarthria, and Kidney Failure","Hemoglobin (g/dl)   6.3
Hematocrit (%)   19.8
White-cell count (per μl)   11,960
Differential count (%)
Neutrophils   89.0
Lymphocytes   6.4
Monocytes 4. .0 3.4
Eosinophils 0. .0 0.3
Basophils 0. .0 0.3
Platelet count (per μl)   347,000
Erythrocyte sedimentation rate 
(mm/hr)
  67
Sodium (mmol/liter)   141
Potassium (mmol/liter)   3.9
Chloride (mmol/liter)   106
Carbon dioxide (mmol/liter)   9
Anion gap (mmol/liter)   26
Urea nitrogen (mg/dl)   124
Creatinine (mg/dl)   16.1
Glucose (mg/dl)   128
Calcium (mg/dl)   7.0
Magnesium (mg/dl)   2.0
Phosphorus (mg/dl)   10.7
Protein (g/dl)
Total 6. .3 6.0
Albumin   3.2
Globulin   2.9
Lactic acid (mmol/liter)   0.7
Creatine kinase (U/liter)   124
C-reactive protein (mg/liter)  .0 32.2
Serum protein electrophoresis Normal pattern
IgG (mg/dl)   616
IgA (mg/dl)   220
IgM (mg/dl)   299
Kappa light chain (mg/liter)   150.9
Lambda light chain (mg/liter)   71.5
Iron (μg/dl) 45–160 85
Iron-binding capacity (μg/dl) 23 4 130
Ferritin (μg/liter) 2 00 689                                                                                   Urinary Laboratory Data                                                                                      Color and clarity Yellow and clear Yellow and clear
pH   6.0
Specific gravity   1.010
Protein Negative 3+
Glucose Negative 2+
Ketones Negative Negative
Blood Negative 1+
Bilirubin Negative Negative
Red cells (per high-power field)   1 0
Leukocytes (per high-power field)    
Creatinine (mg/dl) NA 60
Albumin (mg/dl)  263.3
Albumin:creatinine ratio  4388.3
Total protein (mg/dl) 412.0
Total protein:creatinine ratio  6.87",AA amyloidosis complicated by cerebral mucormycosis.,AA amyloidosis and fungal brain abscess related to injection-drug use.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 37-year-old man was admitted to this hospital because of a facial droop, dysarthria, and kidney failure.
The patient had been well until 1 week before admission, when weakness of the right arm and hand developed, along with difficulty with balance while walking. Two days before admission, the patient was told by family members that his speech sounded slurred while he was speaking on the telephone. On the day of admission, the family members noticed that the patient had new facial asymmetry that had not been present 2 months earlier; in addition, he paused for extended periods of time before answering questions and spoke with slow and slurred speech. The family members brought the patient to the emergency department of this hospital for evaluation.
On evaluation, the patient reported malaise and lethargy. He vomited once in the emergency department but reported no nausea or abdominal or flank pain. He had no fever, chills, headache, vision changes, dysuria, hematuria, or urinary frequency or urgency. There was a history of depression, anxiety, and attention deficit-hyperactivity disorder. The patient had used heroin intravenously since he was 16 years of age and frequently missed veins during injections; his last injection was on the morning of this evaluation. On rare occasions, he had used cocaine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, amphetamines, prescription opiates, benzodiazepines, and marijuana. He had smoked one pack of cigarettes daily for the past 20 years and seldom drank alcohol. The patient had previously been homeless, but at the time of this evaluation, he was living alone in an apartment. He was unemployed but had previously worked in international nonprofit consulting. He had never been sexually active. His father, brother, sister, and paternal cousin had substance use disorders; his mother was healthy. The patient took no medications and had no known drug allergies.
The temperature was 36.8[degrees]C, the blood pressure 130/86 mm Hg, the pulse 92 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 26.6. The patient appeared chronically ill, with a flat affect. He was alert and oriented but had difficulty stating the days of the week backward. He was able to follow simple commands after a delay. His speech was slow and dysarthric. There was a facial droop on the right side. The pupils were equal, round, and reactive to light. Strength was 4+/5 in the right arm and 5-/5 in the right leg. Pronator drift was present on the right side. Strength was normal in the left arm and leg. Sensation and deep-tendon reflexes were normal. The Babinski reflex was present in the right foot. Dorsiflexion of the ankles was followed by seven beats of clonus on the right foot and three on the left foot. There was intermittent spontaneous shaking of the right leg in episodes of approximately 10 seconds in duration. Examination of the skin revealed multiple track marks on the arms, with scattered areas of erythematous induration without fluctuance or tenderness. The remainder of the examination was normal.
Results of liver-function tests were normal, as were results of routine urine and blood toxicologic screening. The blood level of urea nitrogen was 124 mg per deciliter (44.3 mmol per liter; reference range, 8 to 25 mg per deciliter [2.9 to 8.9 mmol per liter]), creatinine 16.1 mg per deciliter (1423 [mu]mol per liter; reference range, 0.6 to 1.5 mg per deciliter [53 to 133 [mu]mol per liter]), and carbon dioxide 9 mmol per liter (reference range, 23 to 32). Four years before this evaluation, the creatinine level had been normal. Other laboratory test results are shown in Table 1 and Table 2. Examination of the urinary sediment revealed granular casts and scattered white cells, with no cellular casts. Tests for antinuclear antibodies, anti-double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies (ANCAs), and rheumatoid factor were negative. Blood levels of C3, C4, lactate dehydrogenase, and glycated hemoglobin were normal. Blood samples were obtained for culture. Screening for human immunodeficiency virus (HIV) type 1 and 2 antibodies and p24 antigen was nonreactive; plasma HIV type 1 RNA was not detected. Tests for hepatitis B virus (HBV) core IgM, hepatitis C virus (HCV) antibodies, Treponema pallidum antibodies, and Toxoplasma gondii antibodies were negative. An interferon-[gamma] release assay for Mycobacterium tuberculosis was negative, and 1,3-[beta]-d-glucan was not detected on a blood test. Imaging studies were obtained.	
Table 1 
Dr. Otto Rapalino: Computed tomography (CT) of the head (Figure 1A), performed without the administration of intravenous contrast material, revealed areas of ill-defined hypoattenuation in the deep frontal white matter and striatal region on the left side. Magnetic resonance imaging of the head (Figure 1B through 1F), performed without the administration of intravenous contrast material, revealed an expansile lesion in the deep gray nuclei and deep white matter on the left side that was associated with signal hyperintensity on T2-weighted and fluid-attenuated inversion recovery imaging and with increased perfusion on arterial spin labeling imaging. Within the abnormality, there was a 4-mm focus of restricted diffusion in the left globus pallidus and the posterior limb of the left internal capsule. There was associated mass effect with partial effacement of the left lateral ventricle and a rightward midline shift of 7 mm.	
Figure 1
Dr. Sanchez: Vancomycin, cefepime, and metronidazole were administered. The patient was admitted to the hospital. Seven hours after antimicrobial therapy was initiated, a lumbar puncture was performed for cerebrospinal fluid (CSF) analysis. The opening pressure was 23 cm of water, and the CSF was colorless. The glucose and total protein levels were normal, the total nucleated-cell count was 1 per microliter (reference range, 0 to 5), and the red-cell count was 61 per microliter (reference range, 0 to 5). Gram's staining of the CSF revealed a moderate amount of mononuclear cells, rare polymorphonucleocytes, and no organisms.
Dr. Rapalino: The next day, renal ultrasonography (Figure 2) revealed mildly enlarged kidneys (right kidney measuring 12.7 cm in length and left kidney 13.5 cm; reference range, 10.1 to 12.8)1 with normal parenchymal echotexture. The left kidney had multiple simple-appearing cysts, and there was no hydronephrosis. CT of the chest, abdomen, and pelvis, performed without the administration of intravenous contrast material, revealed splenomegaly but was otherwise unremarkable.	
Figure 2 
Dr. Sanchez: On the third hospital day, comprehensive transthoracic echocardiography revealed a left ventricular ejection fraction of 66% with no valvular abnormalities; these findings were confirmed on transesophageal echocardiography. During the next 3 days, the patient's neurologic deficits did not improve. Fluids containing sodium bicarbonate were administered intravenously; the carbon dioxide level increased to 19 mmol per liter. The creatinine level decreased to 10.5 mg per deciliter (928 [mu]mol per liter). No Bence Jones protein was detected in urine. Cultures of blood and CSF samples obtained 72 hours earlier were without growth. On the fourth hospital day, the patient reported more fatigue; there were more errors in his speech, and he was slower to respond to questions. Positron-emission tomography of the skull base to midthighs, performed after the intravenous administration of 18F-fluorodeoxyglucose (FDG) tracer, revealed nonspecific foci of moderate FDG uptake in a multinodular goiter but showed no other abnormal FDG uptake.
On the sixth hospital day, seizurelike activity was observed. Lorazepam and levetiracetam were administered. On a repeat blood test, the 1,3-[beta]-d-glucan level was 256 pg per milliliter (reference range, <60). A stereotactic biopsy of the lesion involving the left internal capsule was performed with CT guidance, and grossly purulent material was aspirated. Pathological examination revealed debris with abundant neutrophils and fungal hyphae.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 37-year-old man was admitted to this hospital because of a facial droop, dysarthria, and kidney failure.
The patient had been well until 1 week before admission, when weakness of the right arm and hand developed, along with difficulty with balance while walking. Two days before admission, the patient was told by family members that his speech sounded slurred while he was speaking on the telephone. On the day of admission, the family members noticed that the patient had new facial asymmetry that had not been present 2 months earlier; in addition, he paused for extended periods of time before answering questions and spoke with slow and slurred speech. The family members brought the patient to the emergency department of this hospital for evaluation.
On evaluation, the patient reported malaise and lethargy. He vomited once in the emergency department but reported no nausea or abdominal or flank pain. He had no fever, chills, headache, vision changes, dysuria, hematuria, or urinary frequency or urgency. There was a history of depression, anxiety, and attention deficit-hyperactivity disorder. The patient had used heroin intravenously since he was 16 years of age and frequently missed veins during injections; his last injection was on the morning of this evaluation. On rare occasions, he had used cocaine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, amphetamines, prescription opiates, benzodiazepines, and marijuana. He had smoked one pack of cigarettes daily for the past 20 years and seldom drank alcohol. The patient had previously been homeless, but at the time of this evaluation, he was living alone in an apartment. He was unemployed but had previously worked in international nonprofit consulting. He had never been sexually active. His father, brother, sister, and paternal cousin had substance use disorders; his mother was healthy. The patient took no medications and had no known drug allergies.
The temperature was 36.8[degrees]C, the blood pressure 130/86 mm Hg, the pulse 92 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 26.6. The patient appeared chronically ill, with a flat affect. He was alert and oriented but had difficulty stating the days of the week backward. He was able to follow simple commands after a delay. His speech was slow and dysarthric. There was a facial droop on the right side. The pupils were equal, round, and reactive to light. Strength was 4+/5 in the right arm and 5-/5 in the right leg. Pronator drift was present on the right side. Strength was normal in the left arm and leg. Sensation and deep-tendon reflexes were normal. The Babinski reflex was present in the right foot. Dorsiflexion of the ankles was followed by seven beats of clonus on the right foot and three on the left foot. There was intermittent spontaneous shaking of the right leg in episodes of approximately 10 seconds in duration. Examination of the skin revealed multiple track marks on the arms, with scattered areas of erythematous induration without fluctuance or tenderness. The remainder of the examination was normal.
Results of liver-function tests were normal, as were results of routine urine and blood toxicologic screening. The blood level of urea nitrogen was 124 mg per deciliter (44.3 mmol per liter; reference range, 8 to 25 mg per deciliter [2.9 to 8.9 mmol per liter]), creatinine 16.1 mg per deciliter (1423 [mu]mol per liter; reference range, 0.6 to 1.5 mg per deciliter [53 to 133 [mu]mol per liter]), and carbon dioxide 9 mmol per liter (reference range, 23 to 32). Four years before this evaluation, the creatinine level had been normal. Other laboratory test results are shown in Table 1 and Table 2. Examination of the urinary sediment revealed granular casts and scattered white cells, with no cellular casts. Tests for antinuclear antibodies, anti-double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies (ANCAs), and rheumatoid factor were negative. Blood levels of C3, C4, lactate dehydrogenase, and glycated hemoglobin were normal. Blood samples were obtained for culture. Screening for human immunodeficiency virus (HIV) type 1 and 2 antibodies and p24 antigen was nonreactive; plasma HIV type 1 RNA was not detected. Tests for hepatitis B virus (HBV) core IgM, hepatitis C virus (HCV) antibodies, Treponema pallidum antibodies, and Toxoplasma gondii antibodies were negative. An interferon-[gamma] release assay for Mycobacterium tuberculosis was negative, and 1,3-[beta]-d-glucan was not detected on a blood test. Imaging studies were obtained.	
Table 1 
Dr. Otto Rapalino: Computed tomography (CT) of the head (Figure 1A), performed without the administration of intravenous contrast material, revealed areas of ill-defined hypoattenuation in the deep frontal white matter and striatal region on the left side. Magnetic resonance imaging of the head (Figure 1B through 1F), performed without the administration of intravenous contrast material, revealed an expansile lesion in the deep gray nuclei and deep white matter on the left side that was associated with signal hyperintensity on T2-weighted and fluid-attenuated inversion recovery imaging and with increased perfusion on arterial spin labeling imaging. Within the abnormality, there was a 4-mm focus of restricted diffusion in the left globus pallidus and the posterior limb of the left internal capsule. There was associated mass effect with partial effacement of the left lateral ventricle and a rightward midline shift of 7 mm.	
Figure 1
Dr. Sanchez: Vancomycin, cefepime, and metronidazole were administered. The patient was admitted to the hospital. Seven hours after antimicrobial therapy was initiated, a lumbar puncture was performed for cerebrospinal fluid (CSF) analysis. The opening pressure was 23 cm of water, and the CSF was colorless. The glucose and total protein levels were normal, the total nucleated-cell count was 1 per microliter (reference range, 0 to 5), and the red-cell count was 61 per microliter (reference range, 0 to 5). Gram's staining of the CSF revealed a moderate amount of mononuclear cells, rare polymorphonucleocytes, and no organisms.
Dr. Rapalino: The next day, renal ultrasonography (Figure 2) revealed mildly enlarged kidneys (right kidney measuring 12.7 cm in length and left kidney 13.5 cm; reference range, 10.1 to 12.8)1 with normal parenchymal echotexture. The left kidney had multiple simple-appearing cysts, and there was no hydronephrosis. CT of the chest, abdomen, and pelvis, performed without the administration of intravenous contrast material, revealed splenomegaly but was otherwise unremarkable.	
Figure 2 
Dr. Sanchez: On the third hospital day, comprehensive transthoracic echocardiography revealed a left ventricular ejection fraction of 66% with no valvular abnormalities; these findings were confirmed on transesophageal echocardiography. During the next 3 days, the patient's neurologic deficits did not improve. Fluids containing sodium bicarbonate were administered intravenously; the carbon dioxide level increased to 19 mmol per liter. The creatinine level decreased to 10.5 mg per deciliter (928 [mu]mol per liter). No Bence Jones protein was detected in urine. Cultures of blood and CSF samples obtained 72 hours earlier were without growth. On the fourth hospital day, the patient reported more fatigue; there were more errors in his speech, and he was slower to respond to questions. Positron-emission tomography of the skull base to midthighs, performed after the intravenous administration of 18F-fluorodeoxyglucose (FDG) tracer, revealed nonspecific foci of moderate FDG uptake in a multinodular goiter but showed no other abnormal FDG uptake.
On the sixth hospital day, seizurelike activity was observed. Lorazepam and levetiracetam were administered. On a repeat blood test, the 1,3-[beta]-d-glucan level was 256 pg per milliliter (reference range, <60). A stereotactic biopsy of the lesion involving the left internal capsule was performed with CT guidance, and grossly purulent material was aspirated. Pathological examination revealed debris with abundant neutrophils and fungal hyphae.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Cerebral Abscess due to Fungal Infection. \n\nThe patient's history of intravenous drug use, along with the presence of multiple track marks on the arms, suggests a high risk for infections, including fungal infections. The patient's symptoms of facial droop, dysarthria, and kidney failure, along with the presence of an expansile lesion in the deep gray nuclei and deep white matter on the left side of the brain, suggest a cerebral abscess. The presence of fungal hyphae in the purulent material aspirated from the lesion during the stereotactic biopsy confirms the diagnosis of a cerebral abscess due to a fungal infection.""
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        ""content"": ""The patient's history of intravenous drug use, along with the presence of kidney failure, facial droop, and dysarthria, suggest a systemic infection. The presence of fungal hyphae in the purulent material aspirated from the lesion in the left internal capsule during the stereotactic biopsy confirms a fungal infection. The elevated 1,3-beta-D-glucan level in the blood is also indicative of a fungal infection. The patient's neurological symptoms can be explained by the presence of the lesion in the left internal capsule, which is likely due to the fungal infection. \n\nDiagnosis: Systemic Fungal Infection.""
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        ""content"": ""The patient is a 37-year-old man with a history of intravenous drug use who presents with facial droop, dysarthria, and kidney failure. The differential diagnosis for this patient includes stroke, infectious causes such as meningitis or endocarditis, and autoimmune diseases such as vasculitis. The patient's history of intravenous drug use also raises the possibility of an infection related to drug use, such as a brain abscess or endocarditis. The patient's neurological symptoms, including facial droop and dysarthria, could be due to a stroke, but the presence of kidney failure suggests a systemic process. The patient's imaging studies reveal an expansile lesion in the deep gray nuclei and deep white matter on the left side, which could be due to an abscess or a mass. The patient's kidney failure and the presence of granular casts in the urine suggest a glomerular process, which could be due to an autoimmune disease such as vasculitis or an infection such as endocarditis. However, the patient's tests for autoimmune diseases were negative, making an autoimmune process less likely. The patient's blood cultures were also negative, making endocarditis less likely. The patient's cerebrospinal fluid analysis revealed a moderate amount of mononuclear cells and no organisms, which is not consistent with meningitis. The patient's biopsy of the lesion involving the left internal capsule revealed debris with abundant neutrophils and fungal hyphae, which is consistent with a fungal infection. Given the patient's history of intravenous drug use, the presence of a lesion in the brain, and the findings on biopsy, the most likely diagnosis is a fungal brain abscess due to intravenous drug use.\n\nDiagnosis: Fungal brain abscess due to intravenous drug use.""
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10.1056/NEJMcpc1916250,Case 10-2020: An 83-Year-Old Man with Pancytopenia and Acute Renal Failure,"Hemoglobin (g/dl) 13.3–16.3 12.8   9.6
Hematocrit (%) 40.0–49.0 37.8   27.8
Platelet count (per μl)   121,000   21,000
White-cell count (per μl) 4500–10,500 4500   3710
Differential count (per μl)
Neutrophils 1500–7800 4000   3370
Lymphocytes 850–4100 200   270
Monocytes 20 00 300   70
Eosinophils 50–600 0   0
Reticulocytes (%) 0.5–2.5 <0.5
Prothrombin time (sec)   14.8
Prothrombin-time international normalized 
ratio
  1.2
Activated partial-thromboplastin time (sec) 22. 6.0 61.8
d-dimer (ng/ml)   >10,000
Fibrinogen (mg/dl) 15 0 144
Sodium (mmol/liter)   139   150
Potassium (mmol/liter) 3.5–5.1 4.6   3.1
Chloride (mmol/liter) 98–107 100   111
Carbon dioxide (mmol/liter) 22–29 21   21
Anion gap (mmol/liter) 6–18 18   18
Urea nitrogen (mg/dl) 6–20 44   95
Creatinine (mg/dl) 0.7–1.2 3.2   6.28
Glucose (mg/dl)   158   122
Calcium (mg/dl) 8.6–10.0 9.8   7.2
Uric acid (mg/dl) 3.6–8.5 8.5
Lactic acid (mmol/liter) 0.2–2.0 2.4   3.1
Creatine kinase (U/liter) 39–308 9390   6290
Lactate dehydrogenase (U/liter) 11 10 2592
Protein (g/dl)
Total 6.6–8.7 7.5 6. .3 5.3
Albumin 3.5–5.2 4.8   2.5
Globulin   2.8
Alanine aminotransferase (U/liter) 5–41 118   195
Aspartate aminotransferase (U/liter) 10–50 38   583
Alkaline phosphatase (U/liter) 40–129 101   100
Haptoglobin (mg/dl) 3 00 277
C-reactive protein (mg/liter)  .0 156.5",Anaplasma phagocytophilum infection.,Anaplasma phagocytophilum infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 83-year-old man was transferred to this hospital because of pancytopenia and acute renal failure.
Five days before this presentation, the patient was found conscious on his bedroom floor; he had been well the previous evening. A caregiver noticed that the patient had new generalized weakness and unsteadiness and was unable to walk with a walker. He was taken to the emergency department of another hospital for evaluation.
The temperature was 38.1[degrees]C, the pulse 103 beats per minute, the blood pressure 165/55 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air. He was alert and oriented to self and date of birth. The cardiac, pulmonary, and abdominal examinations were normal. The creatinine level was 3.2 mg per deciliter (283 [mu]mol per liter; reference range, 0.7 to 1.2 mg per deciliter [62 to 106 [mu]mol per liter]), increased from his baseline level of 2.4 mg per deciliter (212 [mu]mol per liter). Other laboratory test results are shown in Table 1. A chest radiograph showed mild pulmonary congestion. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed a right parietal ventriculoperitoneal shunt terminating in the left lateral ventricle that had been placed 2 years earlier because of normal pressure hydrocephalus. The bilateral ventricles were smaller than they had been on previous imaging studies. An infusion of sodium bicarbonate, a single dose of ceftriaxone, and subcutaneous heparin were administered.	
Table 1 
On the second day at the other hospital, the white-cell count was 3800 per microliter (reference range, 4500 to 10,500), the hemoglobin level 12.8 g per deciliter (reference range, 13.3 to 16.3), and the platelet count 75,000 per microliter (reference range, 150,000 to 400,000). The D-dimer level was 229,926 ng per milliliter (reference range, 0 to 500), the fibrinogen level 180 mg per deciliter (reference range, 200 to 393), the international normalized ratio 1.2 (reference range, 0.9 to 1.1), and the prothrombin time 13.5 seconds (reference range, 10.6 to 13.4). Subcutaneous heparin was stopped. During the next 3 days, pancytopenia worsened and the creatinine level increased. On the fifth hospital day, doxycycline was administered, and the patient was transferred to this hospital for further treatment.
The patient had a history of benign prostatic hypertrophy, chronic kidney disease, normal pressure hydrocephalus, mild dementia, hypertension, hyperlipidemia, and coronary artery disease, which had led to multivessel coronary-artery bypass grafting 14 years earlier and to the placement of drug-eluting coronary stents 11 months before this evaluation. He had been treated for Lyme disease 3 years before this evaluation. Medications included aspirin, clopidogrel, atorvastatin, ezetimibe, isosorbide mononitrate, metoprolol succinate, and amlodipine. Penicillin had reportedly caused anaphylaxis. The patient was a widower and lived in a house in New England with his son, daughter-in-law, and grandson, without pets. He had previously worked as a home inspector; in retirement, he enjoyed reading and spending time outside. The patient used a walker for ambulation and was able to perform most activities of daily living; he required assistance from his family and home health services for activities requiring more advanced executive function. He did not use alcohol, tobacco, or illicit drugs. His mother had had heart disease; his father had had dementia.
The temperature was 37.3[degrees]C, the pulse 93 beats per minute, the blood pressure 153/68 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 90% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.7. On examination, the patient was oriented to self and location. The mucous membranes were dry, and the neck was supple. There was no palpable lymphadenopathy, bruising, or rash. The remainder of the physical examination was normal.
Blood cultures were obtained. Blood levels of vitamin B12 and folate were normal. Other laboratory test results are shown in Table 1.
Dr. Eric W. Zhang: CT of the chest (Figure 1A), performed without the administration of intravenous contrast material, revealed symmetric pulmonary edema and bilateral pleural effusions. There were scattered mildly enlarged mediastinal lymph nodes, measuring up to 1.4 cm in short-axis diameter. CT of the abdomen and pelvis (Figure 1B and 1C), performed without the administration of intravenous contrast material, showed cholelithiasis with trace pericholecystic fluid and mild gallbladder-wall thickening. Follow-up ultrasonography of the right upper quadrant revealed cholelithiasis without evidence of cholecystitis; Murphy's sign was negative.	
Figure 1 
Dr. Mewaldt: Doxycycline and intravenous fluids containing sodium bicarbonate were continued. Metoprolol, amlodipine, and isosorbide mononitrate were administered.
On the second day at this hospital, the hematology service was consulted. Examination of a peripheral-blood smear revealed red cells with hypochromic forms, scattered schistocytes (3 per high-power field), and echinocytes. Atypical neutrophils without dysplasia were present, and there were no immature forms or blasts. The platelets were decreased in number and well granulated, without clumping and with some scattered larger forms.
On the third hospital day, tretinoin (often called all-trans retinoic acid) was administered because of concerns about acute promyelocytic leukemia (APL). On the fourth hospital day, additional diagnostic test results were received
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 83-year-old man was transferred to this hospital because of pancytopenia and acute renal failure.
Five days before this presentation, the patient was found conscious on his bedroom floor; he had been well the previous evening. A caregiver noticed that the patient had new generalized weakness and unsteadiness and was unable to walk with a walker. He was taken to the emergency department of another hospital for evaluation.
The temperature was 38.1[degrees]C, the pulse 103 beats per minute, the blood pressure 165/55 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air. He was alert and oriented to self and date of birth. The cardiac, pulmonary, and abdominal examinations were normal. The creatinine level was 3.2 mg per deciliter (283 [mu]mol per liter; reference range, 0.7 to 1.2 mg per deciliter [62 to 106 [mu]mol per liter]), increased from his baseline level of 2.4 mg per deciliter (212 [mu]mol per liter). Other laboratory test results are shown in Table 1. A chest radiograph showed mild pulmonary congestion. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed a right parietal ventriculoperitoneal shunt terminating in the left lateral ventricle that had been placed 2 years earlier because of normal pressure hydrocephalus. The bilateral ventricles were smaller than they had been on previous imaging studies. An infusion of sodium bicarbonate, a single dose of ceftriaxone, and subcutaneous heparin were administered.	
Table 1 
On the second day at the other hospital, the white-cell count was 3800 per microliter (reference range, 4500 to 10,500), the hemoglobin level 12.8 g per deciliter (reference range, 13.3 to 16.3), and the platelet count 75,000 per microliter (reference range, 150,000 to 400,000). The D-dimer level was 229,926 ng per milliliter (reference range, 0 to 500), the fibrinogen level 180 mg per deciliter (reference range, 200 to 393), the international normalized ratio 1.2 (reference range, 0.9 to 1.1), and the prothrombin time 13.5 seconds (reference range, 10.6 to 13.4). Subcutaneous heparin was stopped. During the next 3 days, pancytopenia worsened and the creatinine level increased. On the fifth hospital day, doxycycline was administered, and the patient was transferred to this hospital for further treatment.
The patient had a history of benign prostatic hypertrophy, chronic kidney disease, normal pressure hydrocephalus, mild dementia, hypertension, hyperlipidemia, and coronary artery disease, which had led to multivessel coronary-artery bypass grafting 14 years earlier and to the placement of drug-eluting coronary stents 11 months before this evaluation. He had been treated for Lyme disease 3 years before this evaluation. Medications included aspirin, clopidogrel, atorvastatin, ezetimibe, isosorbide mononitrate, metoprolol succinate, and amlodipine. Penicillin had reportedly caused anaphylaxis. The patient was a widower and lived in a house in New England with his son, daughter-in-law, and grandson, without pets. He had previously worked as a home inspector; in retirement, he enjoyed reading and spending time outside. The patient used a walker for ambulation and was able to perform most activities of daily living; he required assistance from his family and home health services for activities requiring more advanced executive function. He did not use alcohol, tobacco, or illicit drugs. His mother had had heart disease; his father had had dementia.
The temperature was 37.3[degrees]C, the pulse 93 beats per minute, the blood pressure 153/68 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 90% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 25.7. On examination, the patient was oriented to self and location. The mucous membranes were dry, and the neck was supple. There was no palpable lymphadenopathy, bruising, or rash. The remainder of the physical examination was normal.
Blood cultures were obtained. Blood levels of vitamin B12 and folate were normal. Other laboratory test results are shown in Table 1.
Dr. Eric W. Zhang: CT of the chest (Figure 1A), performed without the administration of intravenous contrast material, revealed symmetric pulmonary edema and bilateral pleural effusions. There were scattered mildly enlarged mediastinal lymph nodes, measuring up to 1.4 cm in short-axis diameter. CT of the abdomen and pelvis (Figure 1B and 1C), performed without the administration of intravenous contrast material, showed cholelithiasis with trace pericholecystic fluid and mild gallbladder-wall thickening. Follow-up ultrasonography of the right upper quadrant revealed cholelithiasis without evidence of cholecystitis; Murphy's sign was negative.	
Figure 1 
Dr. Mewaldt: Doxycycline and intravenous fluids containing sodium bicarbonate were continued. Metoprolol, amlodipine, and isosorbide mononitrate were administered.
On the second day at this hospital, the hematology service was consulted. Examination of a peripheral-blood smear revealed red cells with hypochromic forms, scattered schistocytes (3 per high-power field), and echinocytes. Atypical neutrophils without dysplasia were present, and there were no immature forms or blasts. The platelets were decreased in number and well granulated, without clumping and with some scattered larger forms.
On the third hospital day, tretinoin (often called all-trans retinoic acid) was administered because of concerns about acute promyelocytic leukemia (APL). On the fourth hospital day, additional diagnostic test results were received
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Disseminated intravascular coagulation (DIC) secondary to sepsis. The patient's pancytopenia, elevated D-dimer level, and low fibrinogen level are indicative of DIC, a condition characterized by systemic activation of blood clotting, which results in the formation and deposition of fibrin, leading to microangiopathic hemolytic anemia and potentially to organ dysfunction. The patient's acute renal failure and altered mental status suggest end-organ damage, which can be a result of DIC. The patient's fever and the presence of cholelithiasis with pericholecystic fluid on imaging suggest a possible infectious etiology, such as sepsis, which is a common cause of DIC.""
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        ""content"": ""The patient presents with pancytopenia and acute renal failure. His lab results show an elevated D-dimer level and decreased fibrinogen level, which are indicative of disseminated intravascular coagulation (DIC). DIC is a condition characterized by systemic activation of blood clotting, which results in the formation and deposition of fibrin, leading to microvascular thrombi in various organs and contributing to multiple organ dysfunction syndrome. The patient's peripheral blood smear shows schistocytes, which are fragmented red blood cells, a common finding in DIC. The presence of atypical neutrophils and the absence of immature forms or blasts make a diagnosis of acute promyelocytic leukemia less likely. \n\nDiagnosis: Disseminated Intravascular Coagulation (DIC)""
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        ""content"": ""The patient is an elderly man who presents with pancytopenia, acute renal failure, and generalized weakness. The differential diagnosis for this patient includes sepsis, malignancy, autoimmune disease, and drug-induced pancytopenia. The patient's history of benign prostatic hypertrophy, chronic kidney disease, normal pressure hydrocephalus, mild dementia, hypertension, hyperlipidemia, and coronary artery disease, as well as his advanced age, make him susceptible to sepsis. However, his blood cultures were negative, making sepsis less likely. The patient's CT scans revealed mildly enlarged mediastinal lymph nodes, which could suggest malignancy. However, there were no immature forms or blasts on the peripheral blood smear, making leukemia less likely. The patient's medications include aspirin, clopidogrel, atorvastatin, ezetimibe, isosorbide mononitrate, metoprolol succinate, and amlodipine, some of which have been associated with drug-induced pancytopenia. However, the patient's pancytopenia did not improve after discontinuation of these medications, making drug-induced pancytopenia less likely. The patient's peripheral blood smear revealed red cells with hypochromic forms, scattered schistocytes, and echinocytes, as well as atypical neutrophils without dysplasia. These findings are suggestive of microangiopathic hemolytic anemia (MAHA), which can be caused by thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or disseminated intravascular coagulation (DIC). The patient's elevated D-dimer level and decreased fibrinogen level are suggestive of DIC. However, the patient's prothrombin time and international normalized ratio were normal, making DIC less likely. The patient's acute renal failure and MAHA are suggestive of HUS. However, the patient did not have diarrhea, which is commonly associated with HUS, making HUS less likely. The patient's pancytopenia, MAHA, and acute renal failure are suggestive of TTP.\n\nDiagnosis: Thrombotic thrombocytopenic purpura (TTP) is the most likely diagnosis.""
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10.1056/NEJMcpc1909621,"Case 9-2020: A 64-Year-Old Man with Shortness of Breath, Cough, and Hypoxemia","Hematocrit (%)   33.3 39.2
Hemoglobin (g/dl)   11.3 13.9
White-cell count (per μl)   10,180 6490
Differential count (%)
Neutrophils   80.6 90.4
Lymphocytes   8.1 7.0
Monocytes   8.5 2.6
Eosinophils   2.0 0
Basophils   0.6 0
Platelet count (per μl)   320,000 292,000
Red-cell count (per μl)  3,750,000 4,730,000
Mean corpuscular volume (fl)   90.1 82.9
Sodium (mmol/liter)   133 132
Potassium (mmol/liter)   3.9 2.4
Chloride (mmol/liter)   95 93
Carbon dioxide (mmol/liter)   23 27
Glucose (mg/dl)   126 127
Albumin (g/dl)   2.4
Total protein (g/dl) 6. .3 4.6
Lactic acid (mmol/liter)   2.1 1.3
Troponin T (ng/ml) <0.03  
N-terminal pro–B-type natriuretic peptide (pg/ml)   370 153
d-dimer (ng/ml)   6793","Aspergillus terreus infection associated with toxic effects induced by immune checkpoint inhibitor therapy (pneumonitis, colitis, and motor axonal neuropathy) and metastatic melanoma without evidence of active disease.",Pneumonitis induced by immune checkpoint inhibitor therapy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old man presented to this hospital for evaluation of a mass in the left frontal and left parietal lobes.
Four weeks before this presentation, while residing at his home in Florida, the patient began to have clumsiness of the right upper arm, as well as difficulty writing his name, holding a toothbrush, and coordinating activities with his right hand. Two weeks later, the symptoms in the right hand persisted, and the patient presented to his primary care doctor near his home for evaluation. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed an amorphous hypodensity in the left frontal lobe with associated mild local mass effect. Treatment with oral dexamethasone was initiated, but the patient's symptoms did not resolve. He and his wife subsequently traveled to Boston, and he presented to the emergency department of this hospital for further evaluation and care.
At the emergency department, the patient reported 4 weeks of clumsiness and weakness of the right arm. He had no other symptoms. He had a history of melanoma of the left shoulder and had undergone excision of the affected tissue at another hospital 4 years before this evaluation; a lymph node biopsy had reportedly been negative, and no additional therapy had been administered. Medications included dexamethasone. There were no known drug allergies. He had smoked a few cigars per week for the past 10 years and did not consume alcohol or use illicit drugs. He worked as an executive and lived with his wife, splitting time between Florida and the New England area, where they were renovating their home. He had no known sick contacts. His mother had died of colon cancer at 72 years of age; his father had died of an unknown cause when he was in his 30s.
On examination, the temperature was 36.6[degrees]C, the blood pressure 158/95 mm Hg, the pulse 90 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. Movements of the right hand and fingers were slower and less precise than those of the left hand and fingers. The remainder of the physical examination was normal. Imaging studies were obtained.
Dr. Florian J. Fintelmann: Magnetic resonance imaging (MRI) of the head was performed before and after the administration of intravenous contrast material. An axial T1-weighted image obtained without contrast enhancement showed focal hyperintensity in the left frontal lobe, which corresponded to a ring-enhancing lesion surrounded by edema (Figure 1A through 1C). CT of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed a solid, noncalcified nodule in the right upper lung that measured 2.2 cm in diameter (Figure 1D).	
Figure 1 
Dr. Sullivan: CT-guided fine-needle aspiration of the nodule in the right lung revealed malignant cells consistent with metastatic melanoma. Eleven days later, the brain lesion was resected, and pathological examination of the tissue revealed a malignant tumor consistent with metastatic melanoma. Treatment with dexamethasone, levetiracetam, and omeprazole was started.
One week after the resection procedure, the patient was evaluated at the melanoma center of this hospital. During the next 2 months, he received adjuvant radiation therapy to the cranial resection cavity. The dose of dexamethasone was tapered, and treatment with ipilimumab plus nivolumab was initiated.
Five days after initiation of the second cycle of ipilimumab plus nivolumab therapy (25 days after the initiation of the first cycle of therapy and 3 months after the diagnosis of metastatic melanoma), shortness of breath, cough, and fever developed. The patient presented to the emergency department of this hospital.
On examination, the temperature was 37.2[degrees]C, the blood pressure 108/47 mm Hg, the pulse 92 beats per minute, and the oxygen saturation 48% while the patient was breathing ambient air. He was alert and awake, with no signs of respiratory distress. Examination of the lungs revealed crackles in both bases. The remainder of the examination was normal. Oxygen was administered through a nonrebreather face mask, and imaging studies were obtained.
Dr. Fintelmann: A chest radiograph showed low lung volumes, new diffuse interstitial opacities, and bilateral hilar fullness (Figure 2A). CT of the chest ruled out pulmonary embolism and revealed diffuse ground-glass opacities, interlobular septal thickening, and mild traction bronchiectasis (Figure 2B). These findings were new relative to the baseline staging studies obtained 3 months earlier.	
Figure 2
Dr. Sullivan: The results of blood tests of renal and liver function were normal; other laboratory test results are shown in Table 1. The patient was admitted to the oncology service in this hospital. Nucleic acid testing for influenza A and B viruses was negative, as were tests of a nasopharyngeal swab for adenovirus, metapneumovirus, respiratory syncytial virus, and parainfluenza virus types 1, 2, and 3 antigens. A sputum culture and smear, a mycobacterial culture and smear, and an induced-sputum specimen to test for Pneumocystis jirovecii were obtained.	
Table 1
Treatment decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old man presented to this hospital for evaluation of a mass in the left frontal and left parietal lobes.
Four weeks before this presentation, while residing at his home in Florida, the patient began to have clumsiness of the right upper arm, as well as difficulty writing his name, holding a toothbrush, and coordinating activities with his right hand. Two weeks later, the symptoms in the right hand persisted, and the patient presented to his primary care doctor near his home for evaluation. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed an amorphous hypodensity in the left frontal lobe with associated mild local mass effect. Treatment with oral dexamethasone was initiated, but the patient's symptoms did not resolve. He and his wife subsequently traveled to Boston, and he presented to the emergency department of this hospital for further evaluation and care.
At the emergency department, the patient reported 4 weeks of clumsiness and weakness of the right arm. He had no other symptoms. He had a history of melanoma of the left shoulder and had undergone excision of the affected tissue at another hospital 4 years before this evaluation; a lymph node biopsy had reportedly been negative, and no additional therapy had been administered. Medications included dexamethasone. There were no known drug allergies. He had smoked a few cigars per week for the past 10 years and did not consume alcohol or use illicit drugs. He worked as an executive and lived with his wife, splitting time between Florida and the New England area, where they were renovating their home. He had no known sick contacts. His mother had died of colon cancer at 72 years of age; his father had died of an unknown cause when he was in his 30s.
On examination, the temperature was 36.6[degrees]C, the blood pressure 158/95 mm Hg, the pulse 90 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. Movements of the right hand and fingers were slower and less precise than those of the left hand and fingers. The remainder of the physical examination was normal. Imaging studies were obtained.
Dr. Florian J. Fintelmann: Magnetic resonance imaging (MRI) of the head was performed before and after the administration of intravenous contrast material. An axial T1-weighted image obtained without contrast enhancement showed focal hyperintensity in the left frontal lobe, which corresponded to a ring-enhancing lesion surrounded by edema (Figure 1A through 1C). CT of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed a solid, noncalcified nodule in the right upper lung that measured 2.2 cm in diameter (Figure 1D).	
Figure 1 
Dr. Sullivan: CT-guided fine-needle aspiration of the nodule in the right lung revealed malignant cells consistent with metastatic melanoma. Eleven days later, the brain lesion was resected, and pathological examination of the tissue revealed a malignant tumor consistent with metastatic melanoma. Treatment with dexamethasone, levetiracetam, and omeprazole was started.
One week after the resection procedure, the patient was evaluated at the melanoma center of this hospital. During the next 2 months, he received adjuvant radiation therapy to the cranial resection cavity. The dose of dexamethasone was tapered, and treatment with ipilimumab plus nivolumab was initiated.
Five days after initiation of the second cycle of ipilimumab plus nivolumab therapy (25 days after the initiation of the first cycle of therapy and 3 months after the diagnosis of metastatic melanoma), shortness of breath, cough, and fever developed. The patient presented to the emergency department of this hospital.
On examination, the temperature was 37.2[degrees]C, the blood pressure 108/47 mm Hg, the pulse 92 beats per minute, and the oxygen saturation 48% while the patient was breathing ambient air. He was alert and awake, with no signs of respiratory distress. Examination of the lungs revealed crackles in both bases. The remainder of the examination was normal. Oxygen was administered through a nonrebreather face mask, and imaging studies were obtained.
Dr. Fintelmann: A chest radiograph showed low lung volumes, new diffuse interstitial opacities, and bilateral hilar fullness (Figure 2A). CT of the chest ruled out pulmonary embolism and revealed diffuse ground-glass opacities, interlobular septal thickening, and mild traction bronchiectasis (Figure 2B). These findings were new relative to the baseline staging studies obtained 3 months earlier.	
Figure 2
Dr. Sullivan: The results of blood tests of renal and liver function were normal; other laboratory test results are shown in Table 1. The patient was admitted to the oncology service in this hospital. Nucleic acid testing for influenza A and B viruses was negative, as were tests of a nasopharyngeal swab for adenovirus, metapneumovirus, respiratory syncytial virus, and parainfluenza virus types 1, 2, and 3 antigens. A sputum culture and smear, a mycobacterial culture and smear, and an induced-sputum specimen to test for Pneumocystis jirovecii were obtained.	
Table 1
Treatment decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient initially presented with clumsiness and weakness in his right arm. Imaging revealed a mass in the left frontal and left parietal lobes of his brain, and a nodule in his right lung. Given his history of melanoma, these findings suggest metastatic spread of the melanoma to the brain and lung. After resection of the brain lesion and initiation of immunotherapy, the patient developed respiratory symptoms and imaging showed new diffuse interstitial opacities and bilateral hilar fullness. These findings suggest a drug-induced pneumonitis, a known potential side effect of immunotherapy drugs like ipilimumab and nivolumab.\n\nDiagnosis: Metastatic Melanoma with Drug-Induced Pneumonitis.""
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        ""content"": ""The patient has a history of melanoma and presented with a mass in the left frontal and left parietal lobes, which was later confirmed to be metastatic melanoma. The patient also presented with a solid, noncalcified nodule in the right upper lung, which was also confirmed to be metastatic melanoma. The patient later developed shortness of breath, cough, and fever, and imaging studies revealed diffuse ground-glass opacities, interlobular septal thickening, and mild traction bronchiectasis. These symptoms and findings suggest a lung condition, possibly related to the patient's cancer treatment. Given the patient's history and the timing of the symptoms, the most likely diagnosis is pneumonitis induced by immune checkpoint inhibitors.""
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        ""content"": ""The patient is a 64-year-old man with a history of melanoma who presented with a mass in the left frontal and left parietal lobes. He had symptoms of clumsiness and weakness in the right arm. The patient had a history of melanoma of the left shoulder, which was excised 4 years prior. The MRI of the head showed a ring-enhancing lesion surrounded by edema in the left frontal lobe. CT of the chest, abdomen, and pelvis revealed a solid, noncalcified nodule in the right upper lung. The fine-needle aspiration of the nodule in the right lung revealed malignant cells consistent with metastatic melanoma. The brain lesion was resected, and pathological examination of the tissue revealed a malignant tumor consistent with metastatic melanoma. The patient was treated with dexamethasone, levetiracetam, and omeprazole. He also received adjuvant radiation therapy to the cranial resection cavity and treatment with ipilimumab plus nivolumab. The patient developed shortness of breath, cough, and fever after the initiation of the second cycle of ipilimumab plus nivolumab therapy. The chest radiograph showed low lung volumes, new diffuse interstitial opacities, and bilateral hilar fullness. CT of the chest revealed diffuse ground-glass opacities, interlobular septal thickening, and mild traction bronchiectasis. These findings were new relative to the baseline staging studies obtained 3 months earlier. The results of blood tests of renal and liver function were normal. The patient was admitted to the oncology service in this hospital. Nucleic acid testing for influenza A and B viruses was negative, as were tests of a nasopharyngeal swab for adenovirus, metapneumovirus, respiratory syncytial virus, and parainfluenza virus types 1, 2, and 3 antigens. A sputum culture and smear, a mycobacterial culture and smear, and an induced-sputum specimen to test for Pneumocystis jirovecii were obtained. \n\nThe differential diagnosis for this patient includes metastatic melanoma, lung cancer, and pneumonia. The patient's history of melanoma, the presence of a mass in the left frontal and left parietal lobes, and the presence of a solid, noncalcified nodule in the right upper lung are consistent with metastatic melanoma. The patient's symptoms of shortness of breath, cough, and fever, and the findings of low lung volumes, new diffuse interstitial opacities, and bilateral hilar fullness on the chest radiograph, and diffuse ground-glass opacities, interlobular septal thickening, and mild traction bronchiectasis on the CT of the chest are consistent with pneumonia. However, the negative results of the nucleic acid testing for influenza A and B viruses, the tests of a nasopharyngeal swab for adenovirus, metapneumovirus, respiratory syncytial virus, and parainfluenza virus types 1, 2, and 3 antigens, and the sputum culture and smear, the mycobacterial culture and smear, and the induced-sputum specimen to test for Pneumocystis jirovecii make pneumonia less likely. \n\nDiagnosis: Metastatic melanoma with lung involvement.""
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10.1056/NEJMcpc1913476,Case 8-2020: An 89-Year-Old Man with Recurrent Abdominal Pain and Bloody Stools,"Hemoglobin (g/dl)   11.7 8.8 11.3 9.8 9.4
Hematocrit (%)   37.9 27.7 36.4 30.9 29.4
White-cell count (per μl)   10,140 5590 8030 9220 9670
Differential count (%)
Neutrophils   72.8 52.3 78.2 65.5 72.6
Lymphocytes   17.9 27.5 17.4 21.9 15.0
Monocytes   4.4 10.4 2.6 2.5 2.7
Eosinophils   4.1 8.9 0.9 1.7 0.9
Basophils   0.6 0.7 0 0 0
Bands 8.4 8.8
Platelet count (per μl)   152,000 102,000 129,000 85,000 103,000
Urea nitrogen (mg/dl)   35 27 31 39 36
Creatinine (mg/dl)   1.56 1.32 1.79 1.81 1.32
Albumin (g/dl)   3.8 3.6 3.5 2.3
Cytomegalovirus DNA (IU/ml) 137–9,100,000 421
C-reactive protein (mg/liter)   73.2 263.4
Erythrocyte sedimentation rate 
(mm/hr)
  36 117
IgG   1183 1092
IgA   627 565
IgM   19 12
Serum protein electrophoresis No M component No M component
No M component
Kappa free light chain (mg/liter)   134.9
Lambda free light chain (mg/liter)   72.5",Ulcerative colitis.,Ulcerative colitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 89-year-old man was evaluated at this hospital because of recurrent bloody stools.
Two years before the current evaluation, the patient underwent repair of a right inguinal hernia. After he recovered from that procedure, he had intermittent pain in the right lower quadrant. Four months before the current evaluation, he was admitted to this hospital for diffuse abdominal pain followed by presyncope during an attempt to defecate. Examination was notable for bilateral lower abdominal tenderness and a crescendo-decrescendo systolic murmur (grade 2/6) at the left sternal border. Laboratory test results are shown in Table 1.	
Table 1 
Dr. Lauren A. Roller: Computed tomography (CT) of the abdomen and pelvis (Figure 1A and 1B), performed after the administration of oral but not intravenous contrast material, showed diverticulosis of the descending and sigmoid colon, with focal areas of hyperemia and wall thickening in the distal descending colon. There were atherosclerotic changes in the aorta and aortic branches, with a 36-mm infrarenal aortic aneurysm. Small radiopaque stones were present in the gallbladder and common bile duct.	
Figure 1 
Dr. Lopes: Several bowel movements with loose, nonbloody stools occurred, with a decrease in abdominal pain. Empirical oral ciprofloxacin and metronidazole were prescribed, and the patient was discharged on the third hospital day.
Two months later, the patient was readmitted to this hospital with a 3-week history of progressively bloody stools and crampy, diffuse abdominal pain, which had awakened him from sleep. The pain was worst before bowel movements, which occurred approximately five times per day. Increasing amounts of red blood were present in the stools. The patient reported no fever, anorexia, nausea, or vomiting. Examination revealed abdominal tenderness, primarily in the lower quadrants, and the presence of soft, red-brown, formed stool in the rectal vault that was guaiac-positive. Laboratory test results are shown in Table 1. Two units of packed red cells were transfused. Aspirin was discontinued, and a stool specimen was submitted for microbiologic evaluation.
Dr. Roller: CT of the abdomen and pelvis (Figure 1C), performed after the administration of intravenous and oral contrast material, showed a long segment of circumferential wall thickening in the rectum and sigmoid colon and diverticulosis of the distal descending colon, without diverticulitis.
Dr. Lopes: Empirical treatment with oral ciprofloxacin and metronidazole was started. On the second hospital day, nucleic-acid testing of stool was positive for Clostridioides difficile (formerly Clostridium difficile) toxin; ciprofloxacin was discontinued. Three days later, abdominal discomfort persisted, and there were four or five bowel movements per day with blood and intermittent mucus in the stools. Oral vancomycin therapy was started, and metronidazole was discontinued. During the next 3 days, the frequency of bowel movements decreased to two per day, and the patient was discharged to complete 2 weeks of oral vancomycin therapy.
Two weeks after discharge, the frequency of bowel movements increased to four to six per day, with increasingly bloody stools but without abdominal pain. The dose of vancomycin was increased. During the next week, the frequency of bowel movements with bloody stools increased to eight per day, with intermittent incontinence of stool. The patient was admitted for the third time to this hospital. On examination, there was mild bilateral lower abdominal tenderness. The stool was guaiac-positive, and testing for C. difficile toxin was negative; other laboratory test results are shown in Table 1. Cultures of the stool showed normal enteric flora and no pathogenic bacteria.
On the fifth day, flexible sigmoidoscopy (Figure 2A and 2B) revealed diffusely hemorrhagic, erythematous, congested, eroded, friable mucosa in the sigmoid colon, with spontaneous bleeding and pseudopolyps. Biopsy specimens were obtained.	
Figure 2 
Dr. Lawrence R. Zukerberg: The next day, pathological analysis of the biopsy specimens revealed evidence of markedly active chronic colitis, including surface erosion, neutrophilic cryptitis, crypt loss, and replacement of the lamina propria with a dense lymphoplasmacytic infiltrate (Figure 2C). Scattered cytomegalovirus (CMV) inclusion bodies were detected on immunostaining (Figure 2D).
Dr. Lopes: Ganciclovir therapy was started, and laboratory test results are shown in Table 1. Over the next 4 days, there was no decrease in the number of daily bowel movements, but the number of bloody stools decreased. Intermittent anorexia and crampy lower abdominal pain occurred. Ganciclovir was switched to valganciclovir. Over the next 6 days, the frequency of bowel movements decreased to two to five per day, with a modest decrease in anorexia and abdominal pain. The patient was discharged to a rehabilitation facility.
Two weeks later, the patient had persistently loose, yellow, foul-smelling stools. One week later, bloody stools recurred, and after a marked increase in bloody stools over the following week, the patient was readmitted to this hospital. He reported reduced appetite, an unintentional loss of 3 kg during the past month, tenderness on the left side of the abdomen, and diffuse weakness. A review of systems was negative for fever, other bleeding and bruising, and genitourinary, cardiopulmonary, musculoskeletal, and dermatologic symptoms. There were no specific sick contacts at the rehabilitation facility or residents with reported gastrointestinal illnesses.
The patient's medical history was notable for coronary artery disease, moderate aortic stenosis, hypertension, left ventricular hypertrophy, chronic renal insufficiency, glaucoma, and a thyroid nodule; he had undergone aortocoronary-bypass grafting. Outpatient medications included valganciclovir, simvastatin, cholecalciferol, mirtazapine, a multivitamin, and latanoprost eyedrops, as well as loperamide and diphenoxylate with atropine as needed. There were no adverse reactions to medications.
The patient had retired from military service. He had no recent history of travel. He had last used tobacco three decades earlier, and he did not drink alcohol or use illicit substances. His mother had had coronary artery disease and his father had had a stroke; there was no family history of infectious or autoimmune disease.
The temperature was 36.1[degrees]C, the heart rate 89 beats per minute, the blood pressure 117/58 mm Hg, and the oxygen saturation 98% while the patient was breathing ambient air. He was a frail-appearing elderly man with dry mucous membranes and impaired dentition but no oropharyngeal lesions. Cardiac auscultation revealed a crescendo-decrescendo murmur (grade 2/6) at the left sternal border. An abdominal examination revealed tenderness on palpation of the right lower quadrant, without distention, rebound guarding, or organomegaly. A rectal examination revealed only a few small external hemorrhoids, no palpable fissures or masses, slightly reduced rectal tone, and guaiac-positive, light-red, loose stool with mucus. Peripheral pulses were intact, and there were no rashes. The remainder of the examination was normal.
Blood levels of electrolytes, lactate, bilirubin, amylase, lipase, and troponin T and the results of liver-function tests were normal; other test results are shown in Table 1. Stool testing for C. difficile toxin and Shiga toxin was negative, as was examination of the stool for ova and parasites; a test for Entamoeba histolytica antibodies was also negative. A stool specimen was obtained for culture.
Dr. Roller: CT of the abdomen (Figure 3A and 3B), performed after the administration of intravenous and oral contrast material, revealed diffuse bowel-wall thickening and inflammatory changes involving the rectum and the entire colon. There was again evidence of calcific atherosclerosis in the abdominal aorta and aortic branches, with a 37-mm infrarenal abdominal aortic aneurysm with mural thrombus.	
Figure 3 
Dr. Lopes: Treatment with oral vancomycin and intravenous ganciclovir was started. The patient had bowel movements with bloody stools every 2 to 3 hours. On the second hospital day, flexible sigmoidoscopy (Figure 3C and 3D) revealed diffuse severe colonic inflammation, erythema, edema, friability, and deep ulcerations in the sigmoid colon and rectum.
Dr. Zukerberg: Pathological examination of biopsy specimens of the rectum and sigmoid colon (Figure 3E and 3F) revealed evidence of severely active chronic colitis, including surface ulceration, replacement of the lamina propria with a dense lymphoplasmacytic infiltrate, and rare cholesterol emboli in small vessels. Immunohistochemical stains for CMV, herpes simplex virus types 1 and 2, and adenovirus were negative, as was a shell-vial culture for CMV.
Dr. Lopes: A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 89-year-old man was evaluated at this hospital because of recurrent bloody stools.
Two years before the current evaluation, the patient underwent repair of a right inguinal hernia. After he recovered from that procedure, he had intermittent pain in the right lower quadrant. Four months before the current evaluation, he was admitted to this hospital for diffuse abdominal pain followed by presyncope during an attempt to defecate. Examination was notable for bilateral lower abdominal tenderness and a crescendo-decrescendo systolic murmur (grade 2/6) at the left sternal border. Laboratory test results are shown in Table 1.	
Table 1 
Dr. Lauren A. Roller: Computed tomography (CT) of the abdomen and pelvis (Figure 1A and 1B), performed after the administration of oral but not intravenous contrast material, showed diverticulosis of the descending and sigmoid colon, with focal areas of hyperemia and wall thickening in the distal descending colon. There were atherosclerotic changes in the aorta and aortic branches, with a 36-mm infrarenal aortic aneurysm. Small radiopaque stones were present in the gallbladder and common bile duct.	
Figure 1 
Dr. Lopes: Several bowel movements with loose, nonbloody stools occurred, with a decrease in abdominal pain. Empirical oral ciprofloxacin and metronidazole were prescribed, and the patient was discharged on the third hospital day.
Two months later, the patient was readmitted to this hospital with a 3-week history of progressively bloody stools and crampy, diffuse abdominal pain, which had awakened him from sleep. The pain was worst before bowel movements, which occurred approximately five times per day. Increasing amounts of red blood were present in the stools. The patient reported no fever, anorexia, nausea, or vomiting. Examination revealed abdominal tenderness, primarily in the lower quadrants, and the presence of soft, red-brown, formed stool in the rectal vault that was guaiac-positive. Laboratory test results are shown in Table 1. Two units of packed red cells were transfused. Aspirin was discontinued, and a stool specimen was submitted for microbiologic evaluation.
Dr. Roller: CT of the abdomen and pelvis (Figure 1C), performed after the administration of intravenous and oral contrast material, showed a long segment of circumferential wall thickening in the rectum and sigmoid colon and diverticulosis of the distal descending colon, without diverticulitis.
Dr. Lopes: Empirical treatment with oral ciprofloxacin and metronidazole was started. On the second hospital day, nucleic-acid testing of stool was positive for Clostridioides difficile (formerly Clostridium difficile) toxin; ciprofloxacin was discontinued. Three days later, abdominal discomfort persisted, and there were four or five bowel movements per day with blood and intermittent mucus in the stools. Oral vancomycin therapy was started, and metronidazole was discontinued. During the next 3 days, the frequency of bowel movements decreased to two per day, and the patient was discharged to complete 2 weeks of oral vancomycin therapy.
Two weeks after discharge, the frequency of bowel movements increased to four to six per day, with increasingly bloody stools but without abdominal pain. The dose of vancomycin was increased. During the next week, the frequency of bowel movements with bloody stools increased to eight per day, with intermittent incontinence of stool. The patient was admitted for the third time to this hospital. On examination, there was mild bilateral lower abdominal tenderness. The stool was guaiac-positive, and testing for C. difficile toxin was negative; other laboratory test results are shown in Table 1. Cultures of the stool showed normal enteric flora and no pathogenic bacteria.
On the fifth day, flexible sigmoidoscopy (Figure 2A and 2B) revealed diffusely hemorrhagic, erythematous, congested, eroded, friable mucosa in the sigmoid colon, with spontaneous bleeding and pseudopolyps. Biopsy specimens were obtained.	
Figure 2 
Dr. Lawrence R. Zukerberg: The next day, pathological analysis of the biopsy specimens revealed evidence of markedly active chronic colitis, including surface erosion, neutrophilic cryptitis, crypt loss, and replacement of the lamina propria with a dense lymphoplasmacytic infiltrate (Figure 2C). Scattered cytomegalovirus (CMV) inclusion bodies were detected on immunostaining (Figure 2D).
Dr. Lopes: Ganciclovir therapy was started, and laboratory test results are shown in Table 1. Over the next 4 days, there was no decrease in the number of daily bowel movements, but the number of bloody stools decreased. Intermittent anorexia and crampy lower abdominal pain occurred. Ganciclovir was switched to valganciclovir. Over the next 6 days, the frequency of bowel movements decreased to two to five per day, with a modest decrease in anorexia and abdominal pain. The patient was discharged to a rehabilitation facility.
Two weeks later, the patient had persistently loose, yellow, foul-smelling stools. One week later, bloody stools recurred, and after a marked increase in bloody stools over the following week, the patient was readmitted to this hospital. He reported reduced appetite, an unintentional loss of 3 kg during the past month, tenderness on the left side of the abdomen, and diffuse weakness. A review of systems was negative for fever, other bleeding and bruising, and genitourinary, cardiopulmonary, musculoskeletal, and dermatologic symptoms. There were no specific sick contacts at the rehabilitation facility or residents with reported gastrointestinal illnesses.
The patient's medical history was notable for coronary artery disease, moderate aortic stenosis, hypertension, left ventricular hypertrophy, chronic renal insufficiency, glaucoma, and a thyroid nodule; he had undergone aortocoronary-bypass grafting. Outpatient medications included valganciclovir, simvastatin, cholecalciferol, mirtazapine, a multivitamin, and latanoprost eyedrops, as well as loperamide and diphenoxylate with atropine as needed. There were no adverse reactions to medications.
The patient had retired from military service. He had no recent history of travel. He had last used tobacco three decades earlier, and he did not drink alcohol or use illicit substances. His mother had had coronary artery disease and his father had had a stroke; there was no family history of infectious or autoimmune disease.
The temperature was 36.1[degrees]C, the heart rate 89 beats per minute, the blood pressure 117/58 mm Hg, and the oxygen saturation 98% while the patient was breathing ambient air. He was a frail-appearing elderly man with dry mucous membranes and impaired dentition but no oropharyngeal lesions. Cardiac auscultation revealed a crescendo-decrescendo murmur (grade 2/6) at the left sternal border. An abdominal examination revealed tenderness on palpation of the right lower quadrant, without distention, rebound guarding, or organomegaly. A rectal examination revealed only a few small external hemorrhoids, no palpable fissures or masses, slightly reduced rectal tone, and guaiac-positive, light-red, loose stool with mucus. Peripheral pulses were intact, and there were no rashes. The remainder of the examination was normal.
Blood levels of electrolytes, lactate, bilirubin, amylase, lipase, and troponin T and the results of liver-function tests were normal; other test results are shown in Table 1. Stool testing for C. difficile toxin and Shiga toxin was negative, as was examination of the stool for ova and parasites; a test for Entamoeba histolytica antibodies was also negative. A stool specimen was obtained for culture.
Dr. Roller: CT of the abdomen (Figure 3A and 3B), performed after the administration of intravenous and oral contrast material, revealed diffuse bowel-wall thickening and inflammatory changes involving the rectum and the entire colon. There was again evidence of calcific atherosclerosis in the abdominal aorta and aortic branches, with a 37-mm infrarenal abdominal aortic aneurysm with mural thrombus.	
Figure 3 
Dr. Lopes: Treatment with oral vancomycin and intravenous ganciclovir was started. The patient had bowel movements with bloody stools every 2 to 3 hours. On the second hospital day, flexible sigmoidoscopy (Figure 3C and 3D) revealed diffuse severe colonic inflammation, erythema, edema, friability, and deep ulcerations in the sigmoid colon and rectum.
Dr. Zukerberg: Pathological examination of biopsy specimens of the rectum and sigmoid colon (Figure 3E and 3F) revealed evidence of severely active chronic colitis, including surface ulceration, replacement of the lamina propria with a dense lymphoplasmacytic infiltrate, and rare cholesterol emboli in small vessels. Immunohistochemical stains for CMV, herpes simplex virus types 1 and 2, and adenovirus were negative, as was a shell-vial culture for CMV.
Dr. Lopes: A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's recurrent bloody stools, abdominal pain, and the findings of diffuse bowel-wall thickening and inflammatory changes involving the rectum and the entire colon on CT scan suggest a gastrointestinal disorder. The patient's history of coronary artery disease, aortic stenosis, and aortocoronary-bypass grafting, along with the presence of atherosclerosis in the abdominal aorta and aortic branches, suggest a vascular disease. The pathological examination of biopsy specimens revealing evidence of severely active chronic colitis and rare cholesterol emboli in small vessels, along with the negative results for infectious agents, suggest ischemic colitis due to cholesterol embolization, also known as atheroembolic disease. \n\nDiagnosis: Ischemic Colitis due to Cholesterol Embolization (Atheroembolic Disease)""
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        ""content"": ""The patient is an elderly man with a history of coronary artery disease, aortic stenosis, hypertension, and chronic renal insufficiency. He presents with recurrent bloody stools, abdominal pain, and weight loss. His symptoms have not improved with treatment for Clostridioides difficile and cytomegalovirus, suggesting that these infections are not the primary cause of his symptoms. The patient's CT scans show diffuse bowel-wall thickening and inflammatory changes involving the rectum and the entire colon. Biopsy specimens reveal evidence of severely active chronic colitis and rare cholesterol emboli in small vessels. Given the patient's age and history of atherosclerotic disease, the presence of cholesterol emboli suggests that his colitis may be due to ischemia, or insufficient blood flow to the colon. This is further supported by the fact that his symptoms are worst before bowel movements, which could be due to increased demand for blood flow during defecation. \n\nDiagnosis: Ischemic colitis.""
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        ""content"": ""The patient is an elderly man with a history of coronary artery disease, moderate aortic stenosis, hypertension, left ventricular hypertrophy, chronic renal insufficiency, glaucoma, and a thyroid nodule. He presents with recurrent bloody stools, diffuse abdominal pain, and unintentional weight loss. The differential diagnosis for this patient includes ischemic colitis, inflammatory bowel disease (IBD), diverticular disease, colorectal cancer, and infectious colitis. The patient's age, history of cardiovascular disease, and the presence of atherosclerotic changes in the aorta and aortic branches on CT scan make ischemic colitis a strong possibility. However, the patient's symptoms have been recurrent and progressive over several months, which is less typical for ischemic colitis, which usually presents acutely. IBD is less likely given the patient's age and lack of previous gastrointestinal symptoms. The patient's CT scan shows diverticulosis, but there is no evidence of diverticulitis, making diverticular disease less likely. Colorectal cancer is a possibility given the patient's age and symptoms, but the patient's colonoscopy did not reveal any masses. Infectious colitis is also a possibility, but the patient's stool cultures and tests for C. difficile and Shiga toxin were negative. The patient's biopsy showed evidence of severely active chronic colitis and rare cholesterol emboli in small vessels, which is consistent with ischemic colitis. The patient's symptoms improved with supportive care, which is also consistent with ischemic colitis.\n\nDiagnosis: Ischemic colitis.""
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10.1056/NEJMcpc1913470,Case 7-2020: A 52-Year-Old Man with a Mass in the Left Breast,,"Invasive ductal carcinoma, grade 3, with metastatic carcinoma in 1 of 19 lymph nod","Invasive ductal carcinoma, grade 3, with metastatic carcinoma in 1 of 19 lymph nod","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 52-year-old man was referred to the multidisciplinary breast clinic of this hospital for evaluation and management of invasive ductal carcinoma of the left breast.
Seven weeks before the current evaluation, the patient felt a nontender lump in his left breast. Three weeks later (1 month before the current evaluation), he presented to his primary care physician for evaluation of the breast mass. The temperature was 36.2[degrees]C, the heart rate 91 beats per minute, the blood pressure 126/90 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. The weight was 86.6 kg, the height 185.4 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 25.2. Physical examination was notable for a hard mass, measuring 2 cm in diameter, in the left breast and no palpable lymphadenopathy; the remainder of the examination was normal. Blood levels of electrolytes and results of renal- and liver-function tests were normal. The patient was referred for breast imaging studies, and follow-up in the breast clinic was scheduled.
Dr. Constance D. Lehman: Nineteen days before the current evaluation, the patient underwent imaging studies according to the American College of Radiology appropriateness guidelines.1 For men 25 years of age or older who have suspicious findings on a breast examination, bilateral mammography is first performed; images are obtained from standard craniocaudal and mediolateral oblique views, with a skin marker placed at the site of the palpable mass. If mammography is inconclusive or a suspicious finding is identified, ultrasonography is performed. Because of its high sensitivity and specificity in men, mammography is the test of choice to distinguish breast cancer from benign conditions, such as gynecomastia, in this clinical context.2-4 In this patient, mammography (Figure 1A through 1D) confirmed a round mass with irregular margins and associated heterogeneous calcifications deep to the triangle skin marker placed in the left breast. A subareolar density in the opposite breast had imaging characteristics of benign nodular gynecomastia. Ultrasound evaluation of the suspicious lesion (Figure 1E) confirmed a solid, irregular mass, measuring 2.5 cm by 1.5 cm. According to American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) terminology, the findings were BI-RADS 4, indicating that they were suspicious for cancer, and tissue sampling with core-needle biopsy under ultrasonographic guidance was performed (Figure 1F).5 Ultrasound evaluation of the left axilla revealed a suspicious lymph node, and a biopsy was performed.	
Figure 1 
Dr. Kristen M. Basnet: On histologic examination of the core-needle biopsy specimens of the left breast (Figure 2A), two tissue cores showed cohesive nests and cords of malignant cells with moderate-to-severe nuclear pleomorphism and occasional mitoses, findings consistent with intermediate-grade invasive ductal carcinoma. On examination of a fine-needle aspirate of the abnormal left axillary lymph node (Figure 2B), a cellular smear contained large, cohesive, three-dimensional clusters of atypical cells with large, round-to-oval nuclei and prominent nucleoli in a background of scattered, small lymphocytes, findings consistent with metastatic adenocarcinoma.	
Figure 2 
Dr. Micalizzi: After the results of the biopsies were reported, the patient presented to the multidisciplinary breast clinic of this hospital for further evaluation and treatment. Additional history was obtained. The patient reported feeling generally well. Medical history was notable for deafness in the left ear (after a viral infection at 20 years of age) and seasonal rhinitis; he had undergone a vasectomy. Medications included fexofenadine and daily mometasone nasal spray. He had no known medication allergies. He had no history of tobacco use and rarely drank alcohol. He lived with his wife and two children and worked as an accountant. Family history was notable for breast cancer in his father (diagnosed at 81 years of age) and bilateral breast cancer in a paternal aunt (diagnosed during her 50s and 60s), as well as an unknown type of bone cancer in a paternal uncle (diagnosed in his 20s), brain cancer in another paternal uncle (in his 60s), brain and kidney cancer in a third paternal uncle, pancreatic cancer in a male paternal cousin (in his 50s), and prostate cancer in a second paternal cousin. There was also a history of breast cancer in the maternal grandfather (in his 60s) and colon cancer in a maternal aunt (in her 90s). The patient was of Ashkenazi Jewish ancestry.
Physical examination confirmed a 2-cm retroareolar mass in the left breast without palpable axillary lymphadenopathy. On laboratory studies, the blood level of calcium was 11.1 mg per deciliter (2.78 mmol per liter; reference range, 8.2 to 10.5 mg per deciliter [2.05 to 2.63 mmol per liter]), total bilirubin 1.5 mg per deciliter (26 mmol per liter; reference range, 0.0 to 1.0 mg per deciliter [0 to 17 mmol per liter]), alanine aminotransferase 46 U per liter (reference range, 10 to 55), aspartate aminotransferase 46 U per liter (reference range, 10 to 40), and alkaline phosphatase 45 U per liter (reference range, 45 to 115). The remainder of a basic metabolic panel was normal, as were results of renal-function tests and a complete blood count. Computed tomography of the chest, abdomen, and pelvis and a technetium-99m bone scan showed no evidence of metastatic breast cancer. A referral was made for genetic counseling, and 9 days after the current evaluation, a left modified radical mastectomy was performed. Additional management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 52-year-old man was referred to the multidisciplinary breast clinic of this hospital for evaluation and management of invasive ductal carcinoma of the left breast.
Seven weeks before the current evaluation, the patient felt a nontender lump in his left breast. Three weeks later (1 month before the current evaluation), he presented to his primary care physician for evaluation of the breast mass. The temperature was 36.2[degrees]C, the heart rate 91 beats per minute, the blood pressure 126/90 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. The weight was 86.6 kg, the height 185.4 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 25.2. Physical examination was notable for a hard mass, measuring 2 cm in diameter, in the left breast and no palpable lymphadenopathy; the remainder of the examination was normal. Blood levels of electrolytes and results of renal- and liver-function tests were normal. The patient was referred for breast imaging studies, and follow-up in the breast clinic was scheduled.
Dr. Constance D. Lehman: Nineteen days before the current evaluation, the patient underwent imaging studies according to the American College of Radiology appropriateness guidelines.1 For men 25 years of age or older who have suspicious findings on a breast examination, bilateral mammography is first performed; images are obtained from standard craniocaudal and mediolateral oblique views, with a skin marker placed at the site of the palpable mass. If mammography is inconclusive or a suspicious finding is identified, ultrasonography is performed. Because of its high sensitivity and specificity in men, mammography is the test of choice to distinguish breast cancer from benign conditions, such as gynecomastia, in this clinical context.2-4 In this patient, mammography (Figure 1A through 1D) confirmed a round mass with irregular margins and associated heterogeneous calcifications deep to the triangle skin marker placed in the left breast. A subareolar density in the opposite breast had imaging characteristics of benign nodular gynecomastia. Ultrasound evaluation of the suspicious lesion (Figure 1E) confirmed a solid, irregular mass, measuring 2.5 cm by 1.5 cm. According to American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) terminology, the findings were BI-RADS 4, indicating that they were suspicious for cancer, and tissue sampling with core-needle biopsy under ultrasonographic guidance was performed (Figure 1F).5 Ultrasound evaluation of the left axilla revealed a suspicious lymph node, and a biopsy was performed.	
Figure 1 
Dr. Kristen M. Basnet: On histologic examination of the core-needle biopsy specimens of the left breast (Figure 2A), two tissue cores showed cohesive nests and cords of malignant cells with moderate-to-severe nuclear pleomorphism and occasional mitoses, findings consistent with intermediate-grade invasive ductal carcinoma. On examination of a fine-needle aspirate of the abnormal left axillary lymph node (Figure 2B), a cellular smear contained large, cohesive, three-dimensional clusters of atypical cells with large, round-to-oval nuclei and prominent nucleoli in a background of scattered, small lymphocytes, findings consistent with metastatic adenocarcinoma.	
Figure 2 
Dr. Micalizzi: After the results of the biopsies were reported, the patient presented to the multidisciplinary breast clinic of this hospital for further evaluation and treatment. Additional history was obtained. The patient reported feeling generally well. Medical history was notable for deafness in the left ear (after a viral infection at 20 years of age) and seasonal rhinitis; he had undergone a vasectomy. Medications included fexofenadine and daily mometasone nasal spray. He had no known medication allergies. He had no history of tobacco use and rarely drank alcohol. He lived with his wife and two children and worked as an accountant. Family history was notable for breast cancer in his father (diagnosed at 81 years of age) and bilateral breast cancer in a paternal aunt (diagnosed during her 50s and 60s), as well as an unknown type of bone cancer in a paternal uncle (diagnosed in his 20s), brain cancer in another paternal uncle (in his 60s), brain and kidney cancer in a third paternal uncle, pancreatic cancer in a male paternal cousin (in his 50s), and prostate cancer in a second paternal cousin. There was also a history of breast cancer in the maternal grandfather (in his 60s) and colon cancer in a maternal aunt (in her 90s). The patient was of Ashkenazi Jewish ancestry.
Physical examination confirmed a 2-cm retroareolar mass in the left breast without palpable axillary lymphadenopathy. On laboratory studies, the blood level of calcium was 11.1 mg per deciliter (2.78 mmol per liter; reference range, 8.2 to 10.5 mg per deciliter [2.05 to 2.63 mmol per liter]), total bilirubin 1.5 mg per deciliter (26 mmol per liter; reference range, 0.0 to 1.0 mg per deciliter [0 to 17 mmol per liter]), alanine aminotransferase 46 U per liter (reference range, 10 to 55), aspartate aminotransferase 46 U per liter (reference range, 10 to 40), and alkaline phosphatase 45 U per liter (reference range, 45 to 115). The remainder of a basic metabolic panel was normal, as were results of renal-function tests and a complete blood count. Computed tomography of the chest, abdomen, and pelvis and a technetium-99m bone scan showed no evidence of metastatic breast cancer. A referral was made for genetic counseling, and 9 days after the current evaluation, a left modified radical mastectomy was performed. Additional management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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10.1056/NEJMcpc1913475,Case 6-2020: A 34-Year-Old Woman with Hyperglycemia,,Maturity-onset diabetes of the young due to a GCK variant.,"Maturity-onset diabetes of the young, most likely due to a GCK variant.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 34-year-old woman was evaluated in the diabetes clinic of this hospital for hyperglycemia.
Eleven years before this presentation, the blood glucose level was 126 mg per deciliter (7.0 mmol per liter) on routine laboratory evaluation, which was performed as part of an annual well visit. The patient could not recall whether she had been fasting at the time the test had been performed. One year later, the fasting blood glucose level was 112 mg per deciliter (6.2 mmol per liter; reference range,  0 mg per deciliter [<5.6 mmol per liter]).
Nine years before this presentation, a randomly obtained blood glucose level was 217 mg per deciliter (12.0 mmol per liter), and the patient reported polyuria. At that time, the glycated hemoglobin level was 5.8% (reference range, 4.3 to 5.6); the hemoglobin level was normal. One year later, the glycated hemoglobin level was 5.9%. The height was 165.1 cm, the weight 72.6 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 26.6. The patient received a diagnosis of prediabetes and was referred to a nutritionist. She made changes to her diet and lost 4.5 kg of body weight over a 6-month period; the glycated hemoglobin level was 5.5%.
Six years before this presentation, the patient became pregnant with her first child. Her prepregnancy BMI was 24.5. At 26 weeks of gestation, the result of a 1-hour oral glucose challenge test (i.e., the blood glucose level obtained 1 hour after the oral administration of a 50-g glucose load in the nonfasting state) was 186 mg per deciliter (10.3 mmol per liter; reference range, <140 mg per deciliter [<7.8 mmol per liter]). She declined a 3-hour oral glucose tolerance test; a presumptive diagnosis of gestational diabetes was made. She was asked to follow a meal plan for gestational diabetes and was treated with insulin during the pregnancy. Serial ultrasound examinations for fetal growth and monitoring were performed. At 34 weeks of gestation, the fetal abdominal circumference was in the 76th percentile for gestational age. Polyhydramnios developed at 37 weeks of gestation. The child was born at 39 weeks 3 days of gestation, weighed 3.9 kg at birth, and had hypoglycemia after birth, which subsequently resolved. Six weeks post partum, the patient's fasting blood glucose level was 120 mg per deciliter (6.7 mmol per liter), and the result of a 2-hour oral glucose tolerance test (i.e., the blood glucose level obtained 2 hours after the oral administration of a 75-g glucose load in the fasting state) was 131 mg per deciliter (7.3 mmol per liter; reference range, <140 mg per deciliter). Three months post partum, the glycated hemoglobin level was 6.1%. Lifestyle modification for diabetes prevention was recommended.
Four and a half years before this presentation, the patient became pregnant with her second child. Her prepregnancy BMI was 25.1. At 5 weeks of gestation, she had an elevated blood glucose level. Insulin therapy was started at 6 weeks of gestation, and episodes of hypoglycemia occurred during the pregnancy. Serial ultrasound examinations for fetal growth and monitoring were performed. At 28 weeks of gestation, the fetal abdominal circumference was in the 35th percentile for gestational age, and the amniotic fluid level was normal. Labor was induced at 38 weeks of gestation; the child weighed 2.6 kg at birth. Neonatal blood glucose levels were reported as stable after birth. Six weeks post partum, the patient's fasting blood glucose level was 133 mg per deciliter (7.4 mmol per liter), and the result of a 2-hour oral glucose tolerance test was 236 mg per deciliter (13.1 mmol per liter). The patient received a diagnosis of type 2 diabetes mellitus; lifestyle modification was recommended. Three months post partum, the glycated hemoglobin level was 5.9% and the BMI was 30.0. Over the next 2 years, she followed a low-carbohydrate diet and regular exercise plan and self-monitored the blood glucose level.
Two years before this presentation, the patient became pregnant with her third child. Blood glucose levels were again elevated, and insulin therapy was started early in gestation. She had episodes of hypoglycemia that led to adjustment of her insulin regimen. The child was born at 38 weeks 5 days of gestation, weighed 3.0 kg at birth, and had hypoglycemia that resolved 48 hours after birth. After the birth of her third child, the patient started to receive metformin, which had no effect on the glycated hemoglobin level, despite adjustment of the therapy to the maximal dose.
One year before this presentation, the patient became pregnant with her fourth child. Insulin therapy was again started early in gestation. The patient reported that episodes of hypoglycemia occurred. Polyhydramnios developed. The child was born at 38 weeks 6 days of gestation and weighed 3.5 kg. The patient sought care at the diabetes clinic of this hospital for clarification of her diagnosis.
The patient reported following a low-carbohydrate diet and exercising 5 days per week. There was no fatigue, change in appetite, change in vision, chest pain, shortness of breath, polydipsia, or polyuria. There was no history of anemia, pancreatitis, hirsutism, proximal muscle weakness, easy bruising, headache, sweating, tachycardia, gallstones, or diarrhea. Her menstrual periods were normal. She had not noticed any changes in her facial features or the size of her hands or feet.
The patient had a history of acne and low-back pain. Her only medication was metformin. She had no known medication allergies. She lived with her husband and four children in a suburban community in New England and worked as an administrator. She did not smoke tobacco or use illicit drugs, and she rarely drank alcohol. She identified as non-Hispanic white. Both of her grandmothers had type 2 diabetes mellitus. Her father had hypertension, was overweight, and had received a diagnosis of type 2 diabetes at 50 years of age. Her mother was not overweight and had received a diagnosis of type 2 diabetes at 48 years of age. The patient had two sisters, neither of whom had a history of diabetes or gestational diabetes. There was no family history of hemochromatosis.
On examination, the patient appeared well. The blood pressure was 126/76 mm Hg, and the heart rate 76 beats per minute. The BMI was 25.4. The physical examination was normal. The glycated hemoglobin level was 6.2%.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 34-year-old woman was evaluated in the diabetes clinic of this hospital for hyperglycemia.
Eleven years before this presentation, the blood glucose level was 126 mg per deciliter (7.0 mmol per liter) on routine laboratory evaluation, which was performed as part of an annual well visit. The patient could not recall whether she had been fasting at the time the test had been performed. One year later, the fasting blood glucose level was 112 mg per deciliter (6.2 mmol per liter; reference range,  0 mg per deciliter [<5.6 mmol per liter]).
Nine years before this presentation, a randomly obtained blood glucose level was 217 mg per deciliter (12.0 mmol per liter), and the patient reported polyuria. At that time, the glycated hemoglobin level was 5.8% (reference range, 4.3 to 5.6); the hemoglobin level was normal. One year later, the glycated hemoglobin level was 5.9%. The height was 165.1 cm, the weight 72.6 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 26.6. The patient received a diagnosis of prediabetes and was referred to a nutritionist. She made changes to her diet and lost 4.5 kg of body weight over a 6-month period; the glycated hemoglobin level was 5.5%.
Six years before this presentation, the patient became pregnant with her first child. Her prepregnancy BMI was 24.5. At 26 weeks of gestation, the result of a 1-hour oral glucose challenge test (i.e., the blood glucose level obtained 1 hour after the oral administration of a 50-g glucose load in the nonfasting state) was 186 mg per deciliter (10.3 mmol per liter; reference range, <140 mg per deciliter [<7.8 mmol per liter]). She declined a 3-hour oral glucose tolerance test; a presumptive diagnosis of gestational diabetes was made. She was asked to follow a meal plan for gestational diabetes and was treated with insulin during the pregnancy. Serial ultrasound examinations for fetal growth and monitoring were performed. At 34 weeks of gestation, the fetal abdominal circumference was in the 76th percentile for gestational age. Polyhydramnios developed at 37 weeks of gestation. The child was born at 39 weeks 3 days of gestation, weighed 3.9 kg at birth, and had hypoglycemia after birth, which subsequently resolved. Six weeks post partum, the patient's fasting blood glucose level was 120 mg per deciliter (6.7 mmol per liter), and the result of a 2-hour oral glucose tolerance test (i.e., the blood glucose level obtained 2 hours after the oral administration of a 75-g glucose load in the fasting state) was 131 mg per deciliter (7.3 mmol per liter; reference range, <140 mg per deciliter). Three months post partum, the glycated hemoglobin level was 6.1%. Lifestyle modification for diabetes prevention was recommended.
Four and a half years before this presentation, the patient became pregnant with her second child. Her prepregnancy BMI was 25.1. At 5 weeks of gestation, she had an elevated blood glucose level. Insulin therapy was started at 6 weeks of gestation, and episodes of hypoglycemia occurred during the pregnancy. Serial ultrasound examinations for fetal growth and monitoring were performed. At 28 weeks of gestation, the fetal abdominal circumference was in the 35th percentile for gestational age, and the amniotic fluid level was normal. Labor was induced at 38 weeks of gestation; the child weighed 2.6 kg at birth. Neonatal blood glucose levels were reported as stable after birth. Six weeks post partum, the patient's fasting blood glucose level was 133 mg per deciliter (7.4 mmol per liter), and the result of a 2-hour oral glucose tolerance test was 236 mg per deciliter (13.1 mmol per liter). The patient received a diagnosis of type 2 diabetes mellitus; lifestyle modification was recommended. Three months post partum, the glycated hemoglobin level was 5.9% and the BMI was 30.0. Over the next 2 years, she followed a low-carbohydrate diet and regular exercise plan and self-monitored the blood glucose level.
Two years before this presentation, the patient became pregnant with her third child. Blood glucose levels were again elevated, and insulin therapy was started early in gestation. She had episodes of hypoglycemia that led to adjustment of her insulin regimen. The child was born at 38 weeks 5 days of gestation, weighed 3.0 kg at birth, and had hypoglycemia that resolved 48 hours after birth. After the birth of her third child, the patient started to receive metformin, which had no effect on the glycated hemoglobin level, despite adjustment of the therapy to the maximal dose.
One year before this presentation, the patient became pregnant with her fourth child. Insulin therapy was again started early in gestation. The patient reported that episodes of hypoglycemia occurred. Polyhydramnios developed. The child was born at 38 weeks 6 days of gestation and weighed 3.5 kg. The patient sought care at the diabetes clinic of this hospital for clarification of her diagnosis.
The patient reported following a low-carbohydrate diet and exercising 5 days per week. There was no fatigue, change in appetite, change in vision, chest pain, shortness of breath, polydipsia, or polyuria. There was no history of anemia, pancreatitis, hirsutism, proximal muscle weakness, easy bruising, headache, sweating, tachycardia, gallstones, or diarrhea. Her menstrual periods were normal. She had not noticed any changes in her facial features or the size of her hands or feet.
The patient had a history of acne and low-back pain. Her only medication was metformin. She had no known medication allergies. She lived with her husband and four children in a suburban community in New England and worked as an administrator. She did not smoke tobacco or use illicit drugs, and she rarely drank alcohol. She identified as non-Hispanic white. Both of her grandmothers had type 2 diabetes mellitus. Her father had hypertension, was overweight, and had received a diagnosis of type 2 diabetes at 50 years of age. Her mother was not overweight and had received a diagnosis of type 2 diabetes at 48 years of age. The patient had two sisters, neither of whom had a history of diabetes or gestational diabetes. There was no family history of hemochromatosis.
On examination, the patient appeared well. The blood pressure was 126/76 mm Hg, and the heart rate 76 beats per minute. The BMI was 25.4. The physical examination was normal. The glycated hemoglobin level was 6.2%.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of hyperglycemia, gestational diabetes, and type 2 diabetes. She has been on a low-carbohydrate diet and exercises regularly, but her glycated hemoglobin level remains elevated despite lifestyle modifications and metformin therapy. Her family history includes type 2 diabetes in both grandmothers and both parents. Given her history of gestational diabetes, early onset of hyperglycemia, and lack of response to lifestyle modifications and metformin, a form of monogenic diabetes, such as maturity-onset diabetes of the young (MODY), should be considered. MODY is a group of inherited diabetes mellitus characterized by onset usually before 25 years of age, positive family history, and absence of autoantibodies associated with type 1 diabetes. \n\nDiagnosis: Maturity-Onset Diabetes of the Young (MODY)""
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        ""content"": ""The patient is a 34-year-old woman with a history of hyperglycemia, gestational diabetes, and a family history of type 2 diabetes. The differential diagnosis for this patient includes type 2 diabetes, type 1 diabetes, and maturity onset diabetes of the young (MODY). The patient's age, BMI, and family history of type 2 diabetes initially suggest type 2 diabetes. However, her history of gestational diabetes and the fact that she required insulin during her pregnancies suggest that she may have a form of diabetes that is not entirely insulin resistant, such as type 1 diabetes or MODY. The patient does not have symptoms of type 1 diabetes such as weight loss, fatigue, or diabetic ketoacidosis. Furthermore, type 1 diabetes is less likely given her age and the fact that she was able to manage her blood glucose levels with lifestyle modifications and metformin for a period of time. MODY is a form of diabetes that is often misdiagnosed as type 1 or type 2 diabetes. It is characterized by onset at a young age (often before 25 years of age), a strong family history of diabetes, and the absence of obesity. This patient's history is consistent with MODY. She had hyperglycemia at a young age, a strong family history of diabetes, and she is not obese. Furthermore, the fact that she required insulin during her pregnancies and had episodes of hypoglycemia suggests that she has a form of diabetes that involves a defect in insulin secretion, which is characteristic of MODY.\n\nDiagnosis: Maturity onset diabetes of the young (MODY)""
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10.1056/NEJMcpc1900420,Case 5-2020: A 32-Day-Old Male Infant with a Fall,"Hemoglobin (g/dl)   10.7
Hematocrit (%)   30.8
White-cell count (per μl)  13,940
Differential count (%)
Neutrophils 20–46 35
Lymphocytes 5 5 48
Monocytes   15
Eosinophils   2
Platelet count (per μl)   288,000
Red-cell count (per μl) 3,000,000–
5,400,000
3,320,000
Mean corpuscular volume (fl) 85.0–123.0 92.8
Mean corpuscular hemoglobin (pg) 28. .0 32.2
Mean corpuscular hemoglobin 
concentration (g/dl)
29. 7.0 34.7
Red-cell distribution width (fl) 11.5–16.0 14.3
Mean platelet volume (fl) 8.4–12.0 11.0
Description of peripheral smear 1+ polychromasia, 
1+ tear drops
Prothrombin time (sec) 10. .9 14.2
Prothrombin-time international 
normalized ratio
0.8–1.1 1.1
Sodium (mmol/liter)   137
Potassium (mmol/liter)   6.0
Chloride (mmol/liter) 98–106 99
Carbon dioxide (mmol/liter) 22–27 21
Anion gap (mmol/liter)   17
Calcium (mg/dl)   10.6
Urea nitrogen (mg/dl) 5–20 7
Creatinine (mg/dl) 0.30–1.00 0.28
Glucose (mg/dl)   98
Protein (g/dl)
Total 6. .3 5.4
Albumin   3.9
Globulin   1.5
Alanine aminotransferase (U/liter)   24
Aspartate aminotransferase (U/liter) 9–80 30
Alkaline phosphatase (U/liter) 15–350 536
Bilirubin (mg/dl)
Total 2. .0 2.4
Direct   0.3","Intraparenchymal and intracranial hemorrhage 
presumably due to birth trauma.","Possible intracranial hemorrhage at parturition due to a bleeding disorder, most likely von Willebrand’s disease.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 32-day-old male infant was transferred to the emergency department and admitted to this hospital for evaluation of suspected abusive head trauma.
On the evening of admission, the patient's mother called emergency medical services and reported that the patient had fallen. The mother reported that the infant had been well until that evening, when she placed him on her bed before briefly stepping a short distance away to warm up a bottle of formula in the microwave. She heard a thud and then returned to find that the baby had fallen less than 1 m (2 to 3 ft) from the bed to the hardwood floor, where he was lying face down and crying. She picked him up immediately to console him. After continuing to cry for several minutes, the patient suddenly became quiet; this behavior was worrisome to the mother and prompted her to call for emergency medical assistance. During the phone call, the baby resumed crying. On arrival of emergency medical services personnel several minutes later, the infant appeared well and was bottle-feeding without difficulty; there were no signs of injury. He was transported by ambulance to the emergency department of another hospital for evaluation.
At the other hospital, the patient's mother reported that the baby had not lost consciousness or vomited during the event and was behaving normally. On examination, the patient was alert, regarded the examiner, cried when he was undressed, and calmed when he was swaddled. The vital signs were normal. The head was normocephalic and atraumatic. There were no bruises or subconjunctival hemorrhages, and results of abdominal, musculoskeletal, and neurologic examinations were normal, as was the remainder of the physical examination.
Dr. Paul A. Caruso: Computed tomography (CT) of the head, performed without the administration of contrast material, revealed scattered punctate densities in the right and left superior occipital lobes, a density (3 mm in diameter) extending along the left tentorial leaflet, mild prominence of both opercula, and mild diffuse prominence of the extraaxial spaces (Figure 1).	
Figure 1 
Dr. Keyes: A report of suspected abusive head trauma was filed with the Massachusetts Department of Children and Families, and the patient was transferred to the emergency department of this hospital for further evaluation.
On arrival at this hospital, a history was obtained from the patient's mother. The patient was born at another hospital after 37 weeks of gestation; labor was induced because of maternal preeclampsia, and the infant was delivered vaginally. At delivery, a nuchal cord was unwrapped from the baby's neck. He received routine newborn care and was feeding and growing well. Two weeks before the current evaluation, he was seen in the emergency department of the first hospital because of three episodes of vomiting; abdominal ultrasonography performed during that visit did not reveal findings consistent with pyloric stenosis. During the 10 to 14 days before the current evaluation, the patient was fussy. He had a diaper rash, for which his pediatrician prescribed topical nystatin; in addition, his mother was applying a zinc oxide-containing cream to the rash. He took no other medications and had no known allergies. His mother had a history of asthma, post-traumatic stress disorder, and anxiety; she had placed frequent calls to emergency medical services because of concerns about her health but was often reassured by the responding personnel and not transported to a hospital. Both of the patient's maternal grandparents had a history of substance use disorder, and his maternal grandmother had died of a heroin overdose.
The patient lived with his mother in housing funded by the Department of Mental Health. They were visited each week by a case manager and received social support from an aunt. The patient's mother was a high school graduate and was certified as an emergency medical technician; she had been in the custody of the Department of Children and Families during adolescence and had a 2-year-old daughter who had been placed with the aunt at the recommendation of the Department of Children and Families because of concerns about the mother's mental health issues. Although the case involving the daughter was closed, the mother reported that she still had contact with her former social worker, who continued to provide support. The pregnancy with the patient was unplanned and occurred near the beginning of the mother's relationship with the father of the baby; this relationship was characterized by young age and intimate-partner violence, and the couple separated before the birth of the infant. The mother was the patient's primary caregiver, although on two occasions (the most recent one occurring 6 days before this evaluation), the baby had spent time with his father.
On examination, the patient was alert and vigorous and appeared well. The temperature was 36.6[degrees]C, the pulse 161 beats per minute, the blood pressure 86/50 mm Hg, the respiratory rate 56 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. The weight was 3.99 kg (18th percentile), the length 53 cm (17th percentile), and the head circumference 35 cm (2nd percentile). There were no exterior signs of facial or scalp trauma, and the anterior fontanelle was soft and flat. An intraoral examination did not reveal lesions; the lingual frenulum was intact. The abdomen was soft, without distention, tenderness, or masses. Examination of the skin revealed scattered skin-colored papules (1 mm in diameter) on the chest and face, a crescent-shaped erythematous patch above the right nipple, a blanching erythematous macule (3 mm in diameter) on the left buttock, erythema of the intergluteal cleft, and a scratch (3 mm by 2 mm) behind the left knee. The remainder of the physical examination was normal. Laboratory test results are shown in Table 1. The patient was admitted to the hospital, and additional imaging studies were obtained.	
Table 1 
Dr. Caruso: Susceptibility-weighted magnetic resonance imaging (MRI), performed 16 hours after the head CT, revealed a lobular focus of hemorrhage (15 mm by 2 mm) in the right superior occipital gyrus that was probably chronic and corresponded to the 2-mm punctate density seen on non-contrast-enhanced CT. A similar focus of hemorrhage in the left superior occipital gyrus was also probably chronic. A focus of hemorrhage in the right caudothalamic groove and two foci of hemorrhage or mineralization (3 mm in diameter) in the bilateral choroid plexuses were also seen (Figure 2).	
Figure 2 
Dr. Keyes: Additional evaluation was performed, and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 32-day-old male infant was transferred to the emergency department and admitted to this hospital for evaluation of suspected abusive head trauma.
On the evening of admission, the patient's mother called emergency medical services and reported that the patient had fallen. The mother reported that the infant had been well until that evening, when she placed him on her bed before briefly stepping a short distance away to warm up a bottle of formula in the microwave. She heard a thud and then returned to find that the baby had fallen less than 1 m (2 to 3 ft) from the bed to the hardwood floor, where he was lying face down and crying. She picked him up immediately to console him. After continuing to cry for several minutes, the patient suddenly became quiet; this behavior was worrisome to the mother and prompted her to call for emergency medical assistance. During the phone call, the baby resumed crying. On arrival of emergency medical services personnel several minutes later, the infant appeared well and was bottle-feeding without difficulty; there were no signs of injury. He was transported by ambulance to the emergency department of another hospital for evaluation.
At the other hospital, the patient's mother reported that the baby had not lost consciousness or vomited during the event and was behaving normally. On examination, the patient was alert, regarded the examiner, cried when he was undressed, and calmed when he was swaddled. The vital signs were normal. The head was normocephalic and atraumatic. There were no bruises or subconjunctival hemorrhages, and results of abdominal, musculoskeletal, and neurologic examinations were normal, as was the remainder of the physical examination.
Dr. Paul A. Caruso: Computed tomography (CT) of the head, performed without the administration of contrast material, revealed scattered punctate densities in the right and left superior occipital lobes, a density (3 mm in diameter) extending along the left tentorial leaflet, mild prominence of both opercula, and mild diffuse prominence of the extraaxial spaces (Figure 1).	
Figure 1 
Dr. Keyes: A report of suspected abusive head trauma was filed with the Massachusetts Department of Children and Families, and the patient was transferred to the emergency department of this hospital for further evaluation.
On arrival at this hospital, a history was obtained from the patient's mother. The patient was born at another hospital after 37 weeks of gestation; labor was induced because of maternal preeclampsia, and the infant was delivered vaginally. At delivery, a nuchal cord was unwrapped from the baby's neck. He received routine newborn care and was feeding and growing well. Two weeks before the current evaluation, he was seen in the emergency department of the first hospital because of three episodes of vomiting; abdominal ultrasonography performed during that visit did not reveal findings consistent with pyloric stenosis. During the 10 to 14 days before the current evaluation, the patient was fussy. He had a diaper rash, for which his pediatrician prescribed topical nystatin; in addition, his mother was applying a zinc oxide-containing cream to the rash. He took no other medications and had no known allergies. His mother had a history of asthma, post-traumatic stress disorder, and anxiety; she had placed frequent calls to emergency medical services because of concerns about her health but was often reassured by the responding personnel and not transported to a hospital. Both of the patient's maternal grandparents had a history of substance use disorder, and his maternal grandmother had died of a heroin overdose.
The patient lived with his mother in housing funded by the Department of Mental Health. They were visited each week by a case manager and received social support from an aunt. The patient's mother was a high school graduate and was certified as an emergency medical technician; she had been in the custody of the Department of Children and Families during adolescence and had a 2-year-old daughter who had been placed with the aunt at the recommendation of the Department of Children and Families because of concerns about the mother's mental health issues. Although the case involving the daughter was closed, the mother reported that she still had contact with her former social worker, who continued to provide support. The pregnancy with the patient was unplanned and occurred near the beginning of the mother's relationship with the father of the baby; this relationship was characterized by young age and intimate-partner violence, and the couple separated before the birth of the infant. The mother was the patient's primary caregiver, although on two occasions (the most recent one occurring 6 days before this evaluation), the baby had spent time with his father.
On examination, the patient was alert and vigorous and appeared well. The temperature was 36.6[degrees]C, the pulse 161 beats per minute, the blood pressure 86/50 mm Hg, the respiratory rate 56 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. The weight was 3.99 kg (18th percentile), the length 53 cm (17th percentile), and the head circumference 35 cm (2nd percentile). There were no exterior signs of facial or scalp trauma, and the anterior fontanelle was soft and flat. An intraoral examination did not reveal lesions; the lingual frenulum was intact. The abdomen was soft, without distention, tenderness, or masses. Examination of the skin revealed scattered skin-colored papules (1 mm in diameter) on the chest and face, a crescent-shaped erythematous patch above the right nipple, a blanching erythematous macule (3 mm in diameter) on the left buttock, erythema of the intergluteal cleft, and a scratch (3 mm by 2 mm) behind the left knee. The remainder of the physical examination was normal. Laboratory test results are shown in Table 1. The patient was admitted to the hospital, and additional imaging studies were obtained.	
Table 1 
Dr. Caruso: Susceptibility-weighted magnetic resonance imaging (MRI), performed 16 hours after the head CT, revealed a lobular focus of hemorrhage (15 mm by 2 mm) in the right superior occipital gyrus that was probably chronic and corresponded to the 2-mm punctate density seen on non-contrast-enhanced CT. A similar focus of hemorrhage in the left superior occipital gyrus was also probably chronic. A focus of hemorrhage in the right caudothalamic groove and two foci of hemorrhage or mineralization (3 mm in diameter) in the bilateral choroid plexuses were also seen (Figure 2).	
Figure 2 
Dr. Keyes: Additional evaluation was performed, and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Abusive head trauma (Shaken Baby Syndrome). The infant's mother's history of mental health issues, the history of intimate-partner violence, and the fact that the baby had been left alone on a bed from which he could fall, all raise concerns about the possibility of child abuse. The CT and MRI findings of multiple foci of hemorrhage in the brain are consistent with abusive head trauma, often seen in shaken baby syndrome.""
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        ""content"": ""The infant presents with a history of a fall and subsequent change in behavior, which prompted the mother to seek medical attention. The physical examination was largely unremarkable, with no signs of external trauma. However, imaging studies revealed multiple foci of hemorrhage in the brain. The differential diagnosis for this presentation includes accidental trauma, non-accidental trauma (child abuse), and a bleeding disorder. The history provided by the mother of a short fall is not consistent with the severity of the intracranial findings, making accidental trauma less likely. A bleeding disorder could potentially cause spontaneous hemorrhages, but there is no mention of abnormal coagulation studies or other signs of a bleeding disorder, such as bruising or petechiae. The social history raises several red flags for potential child abuse, including a history of intimate partner violence, mental health issues, and previous involvement with child protective services. The presence of multiple, bilateral, and chronic hemorrhages on imaging is also highly suggestive of non-accidental trauma, as these findings are often seen in abusive head trauma (also known as shaken baby syndrome). \n\nDiagnosis: Abusive head trauma (Shaken Baby Syndrome)""
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10.1056/NEJMcpc1913471,Case 4-2020: A 52-Year-Old Woman with Seizure Disorder and Wide-Complex Tachycardia,"Hemoglobin (g/dl)   11.8 10.2
Hematocrit (%)   35.5 31.7
White-cell count (per μl)   3.93 12.81
Platelet count (per μl)   281,000 307,000
Sodium (mmol/liter)   140 145
Potassium (mmol/liter)   4.5 3.8
Chloride (mmol/liter)   95 115
Carbon dioxide (mmol/liter)   25 19
Urea nitrogen (mg/dl)   14 13
Creatinine (mg/dl)   0.65 0.45
Glucose (mg/dl)   104 152
Phosphorus (mg/dl)   4.6 2.6
Magnesium (mg/dl)   1.7 2.2
Calcium (mg/dl)   9.3 7.3
Total protein (g/dl) 6. .3 7.1 4.8
Albumin (g/dl)   4.4 2.4
Lactate (mmol/liter)   5.8 1.7
Troponin T (ng/ml) <0.03  
Venous blood gas
pH   7.28
Partial pressure of carbon dioxide (mm Hg)   59
Partial pressure of oxygen (mm Hg) 35–30 49
Arterial blood gas
Fraction of inspired oxygen 0.60
pH   7.38
Partial pressure of carbon dioxide (mm Hg)   33
Partial pressure of oxygen (mm Hg)   114",Antiepileptic drug toxicity,Antiepileptic drug toxicity.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 52-year-old woman was evaluated for a new wide-complex tachycardia that developed while she was hospitalized for the management of seizures.
Five days before the development of tachycardia, the patient had been admitted to this hospital with tonic-clonic seizure activity. Six days before the current admission, she had been discharged from this hospital after a prolonged hospitalization in the neurosciences intensive care unit (ICU) for refractory status epilepticus. At the time of discharge, she was transferred to a skilled nursing facility for transitional care. Two days after transfer, she had a fall with a reportedly mild head injury; no further evaluation was done.
On the morning of the current admission, the patient had a focal seizure at the skilled nursing facility and diazepam was administered intravenously. After she had another seizure, emergency medical services were contacted. She had a total of seven tonic-clonic seizures, each of which lasted up to 90 seconds. On arrival of emergency medical services, the trachea was intubated and then the patient was transferred to the emergency department of this hospital.
After evaluation in the emergency department, the patient was admitted to the neurosciences ICU. An electrocardiogram (ECG) was obtained on admission (Figure 1A). Propofol, midazolam, and phenobarbital were administered intravenously, and clobazam, felbamate, lacosamide, levetiracetam, and oxcarbazepine were administered through an orogastric tube. Computed tomography of the head, performed without the administration of intravenous contrast material, revealed no intracranial abnormality. Electroencephalographic (EEG) monitoring showed ongoing seizure activity; on the second day, boluses of pentobarbital were administered intravenously. Central venous and arterial catheters were placed so that norepinephrine could be administered to maintain the mean arterial pressure. On the third day, a transient junctional cardiac rhythm was noted, and the administration of pentobarbital boluses was stopped. Periods of sinus bradycardia and ventricular bigeminy were subsequently noted.	
Figure 1 
Dr. Karen A. Buch: On the fourth day, positron-emission tomography (PET) and magnetic resonance imaging (MRI) of the head were performed. There were ill-defined subcortical and cortical hyperintensities in the left occipital lobe on T2-weighted MRI, which corresponded to an area of 18F-fluorodeoxyglucose avidity seen on previous PET (Figure 2).	
Figure 2 
Dr. Mihatov: On the fifth day, ECG abnormalities were noted (Figure 1B). Late that evening, the temperature was 38.4[degrees]C and additional norepinephrine was given. Four hours later, P waves were thought to be absent on telemetric monitoring (Figure 1C). In addition, the QRS complex was noted to be wide, and urgent cardiology consultation was obtained (Figure 1D).
The patient's medical history was notable for seizure disorder, post-traumatic stress disorder (PTSD), and bipolar disorder. Her admission to the neurosciences ICU of this hospital for refractory status epilepticus had begun 3 months earlier. During that admission, PET of the head and EEG suggested a causative focus in the left occipital lobe; other evaluation (a paraneoplastic antibody panel, assessment for infection, lumbar puncture with cerebrospinal fluid analysis, toxicologic screening, and testing for other antibodies, including antinuclear antibodies) was unrevealing. Tracheostomy and gastrostomy were performed as part of the prolonged ICU stay, during which deep sedation was administered to suppress seizure activity. The patient underwent trials of multiple antiepileptic medications: phenytoin caused bradycardia and ventricular bigeminy, and valproic acid was discontinued because of elevated aminotransferase and ammonia levels. Transcranial magnetic stimulation was performed, and seizures were ultimately controlled with a combination of clobazam, felbamate, lacosamide, levetiracetam, and oxcarbazepine.
Medications that the patient had been receiving immediately before the current hospitalization included clobazam, felbamate, fluoxetine, lacosamide, levetiracetam, nortriptyline, oxcarbazepine, prazosin, and folic acid, as well as diazepam and quetiapine as needed. There were no other known adverse reactions to medications. Medications that the patient was receiving at the time of the cardiology consultation included intravenous infusions of propofol, midazolam, and pentobarbital; intravenous vancomycin and piperacillin-tazobactam; subcutaneous enoxaparin injection; and enteral clobazam, felbamate, fluoxetine, lacosamide, levetiracetam, oxcarbazepine, folic acid, senna, polyethylene glycol, and multivitamins.
The patient had been hospitalized nearly continuously for the previous 4 months. She had two children. She had smoked 1 pack of cigarettes weekly for 20 years and had previously consumed alcohol heavily; she also had previously used nonprescribed benzodiazepines. The family history was negative for neurologic and cardiac disease.
On examination, the patient was intubated, sedated, and unresponsive. The temperature was 37.6[degrees]C, the heart rate 98 beats per minute, the blood pressure 106/56 mm Hg while she was receiving norepinephrine, and the oxygen saturation 99% while she was receiving pressure-controlled mechanical ventilation at a rate of 18 breaths per minute (fraction of inspired oxygen, 0.60; inspiratory pressure, 12 cm of water; expiratory pressure, 10 cm of water). The pupils were symmetric and sluggish. Further assessment of neurologic function was limited. The heart sounds were distant, and there was no detectable murmur. Bowel sounds were present. The arms and legs were cool.
Blood levels of alanine aminotransferase, ammonia, aspartate aminotransferase, bilirubin, and triglyceride were normal; other laboratory test results are shown in Table 1. Additional ECGs showed a wide-QRS-complex rhythm of uncertain mechanism. A bedside cardiac ultrasound examination showed diffuse global hypokinesis of the left ventricle.	
Table 1 
A diagnosis and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 52-year-old woman was evaluated for a new wide-complex tachycardia that developed while she was hospitalized for the management of seizures.
Five days before the development of tachycardia, the patient had been admitted to this hospital with tonic-clonic seizure activity. Six days before the current admission, she had been discharged from this hospital after a prolonged hospitalization in the neurosciences intensive care unit (ICU) for refractory status epilepticus. At the time of discharge, she was transferred to a skilled nursing facility for transitional care. Two days after transfer, she had a fall with a reportedly mild head injury; no further evaluation was done.
On the morning of the current admission, the patient had a focal seizure at the skilled nursing facility and diazepam was administered intravenously. After she had another seizure, emergency medical services were contacted. She had a total of seven tonic-clonic seizures, each of which lasted up to 90 seconds. On arrival of emergency medical services, the trachea was intubated and then the patient was transferred to the emergency department of this hospital.
After evaluation in the emergency department, the patient was admitted to the neurosciences ICU. An electrocardiogram (ECG) was obtained on admission (Figure 1A). Propofol, midazolam, and phenobarbital were administered intravenously, and clobazam, felbamate, lacosamide, levetiracetam, and oxcarbazepine were administered through an orogastric tube. Computed tomography of the head, performed without the administration of intravenous contrast material, revealed no intracranial abnormality. Electroencephalographic (EEG) monitoring showed ongoing seizure activity; on the second day, boluses of pentobarbital were administered intravenously. Central venous and arterial catheters were placed so that norepinephrine could be administered to maintain the mean arterial pressure. On the third day, a transient junctional cardiac rhythm was noted, and the administration of pentobarbital boluses was stopped. Periods of sinus bradycardia and ventricular bigeminy were subsequently noted.	
Figure 1 
Dr. Karen A. Buch: On the fourth day, positron-emission tomography (PET) and magnetic resonance imaging (MRI) of the head were performed. There were ill-defined subcortical and cortical hyperintensities in the left occipital lobe on T2-weighted MRI, which corresponded to an area of 18F-fluorodeoxyglucose avidity seen on previous PET (Figure 2).	
Figure 2 
Dr. Mihatov: On the fifth day, ECG abnormalities were noted (Figure 1B). Late that evening, the temperature was 38.4[degrees]C and additional norepinephrine was given. Four hours later, P waves were thought to be absent on telemetric monitoring (Figure 1C). In addition, the QRS complex was noted to be wide, and urgent cardiology consultation was obtained (Figure 1D).
The patient's medical history was notable for seizure disorder, post-traumatic stress disorder (PTSD), and bipolar disorder. Her admission to the neurosciences ICU of this hospital for refractory status epilepticus had begun 3 months earlier. During that admission, PET of the head and EEG suggested a causative focus in the left occipital lobe; other evaluation (a paraneoplastic antibody panel, assessment for infection, lumbar puncture with cerebrospinal fluid analysis, toxicologic screening, and testing for other antibodies, including antinuclear antibodies) was unrevealing. Tracheostomy and gastrostomy were performed as part of the prolonged ICU stay, during which deep sedation was administered to suppress seizure activity. The patient underwent trials of multiple antiepileptic medications: phenytoin caused bradycardia and ventricular bigeminy, and valproic acid was discontinued because of elevated aminotransferase and ammonia levels. Transcranial magnetic stimulation was performed, and seizures were ultimately controlled with a combination of clobazam, felbamate, lacosamide, levetiracetam, and oxcarbazepine.
Medications that the patient had been receiving immediately before the current hospitalization included clobazam, felbamate, fluoxetine, lacosamide, levetiracetam, nortriptyline, oxcarbazepine, prazosin, and folic acid, as well as diazepam and quetiapine as needed. There were no other known adverse reactions to medications. Medications that the patient was receiving at the time of the cardiology consultation included intravenous infusions of propofol, midazolam, and pentobarbital; intravenous vancomycin and piperacillin-tazobactam; subcutaneous enoxaparin injection; and enteral clobazam, felbamate, fluoxetine, lacosamide, levetiracetam, oxcarbazepine, folic acid, senna, polyethylene glycol, and multivitamins.
The patient had been hospitalized nearly continuously for the previous 4 months. She had two children. She had smoked 1 pack of cigarettes weekly for 20 years and had previously consumed alcohol heavily; she also had previously used nonprescribed benzodiazepines. The family history was negative for neurologic and cardiac disease.
On examination, the patient was intubated, sedated, and unresponsive. The temperature was 37.6[degrees]C, the heart rate 98 beats per minute, the blood pressure 106/56 mm Hg while she was receiving norepinephrine, and the oxygen saturation 99% while she was receiving pressure-controlled mechanical ventilation at a rate of 18 breaths per minute (fraction of inspired oxygen, 0.60; inspiratory pressure, 12 cm of water; expiratory pressure, 10 cm of water). The pupils were symmetric and sluggish. Further assessment of neurologic function was limited. The heart sounds were distant, and there was no detectable murmur. Bowel sounds were present. The arms and legs were cool.
Blood levels of alanine aminotransferase, ammonia, aspartate aminotransferase, bilirubin, and triglyceride were normal; other laboratory test results are shown in Table 1. Additional ECGs showed a wide-QRS-complex rhythm of uncertain mechanism. A bedside cardiac ultrasound examination showed diffuse global hypokinesis of the left ventricle.	
Table 1 
A diagnosis and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 52-year-old woman with a history of seizure disorder, PTSD, and bipolar disorder. She was admitted to the hospital for management of seizures and developed a new wide-complex tachycardia. The differential diagnosis for wide-complex tachycardia includes ventricular tachycardia, supraventricular tachycardia with aberrancy, and paced rhythms. Given the patient's history of seizures and the medications she was receiving, drug-induced tachycardia should also be considered. The patient was receiving multiple medications that could potentially affect cardiac rhythm, including propofol, midazolam, and pentobarbital. The patient's ECG showed a wide-QRS-complex rhythm of uncertain mechanism. A bedside cardiac ultrasound examination showed diffuse global hypokinesis of the left ventricle. This could suggest a cardiomyopathy, which could be a cause of ventricular tachycardia. However, the patient's history and presentation are more suggestive of a drug-induced tachycardia. The patient was receiving multiple medications that could potentially affect cardiac rhythm, including propofol, midazolam, and pentobarbital. These medications can cause QT prolongation, which can lead to ventricular tachycardia. The patient's tachycardia developed while she was hospitalized and receiving these medications, which supports the diagnosis of drug-induced tachycardia.\n\nDiagnosis: Drug-induced tachycardia.""
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10.1056/NEJMcpc1913473,"Case 3-2020: A 44-Year-Old Man with Weight Loss, Diarrhea, and Abdominal Pain","Hemoglobin (g/dl)  12.3 12.4   13.2
Hematocrit (%) 37.4 37.8   40.6
White-cell count (per μl) 28,600 10,300   11,170
Differential count (%)
Neutrophils 40. 0.0 63.9 35.9   53.4
Bands  16.8
Immature granulocytes  0.5
Lymphocytes 6.0 5.0 43.3   29.5
Atypical lymphocytes 0 0.8 0 0
Monocytes 9.2 9.7   12.4
Eosinophils 0.8 9.8   5.0
Basophils 0.5 0.6 
Metamyelocytes  3.4 0
Platelet count (per μl)   258,000 415,000   395,000
Sodium (mmol/liter)   133 126   131
Potassium (mmol/liter) 4.0 4.6   4.3
Chloride (mmol/liter) 100 92   98
Carbon dioxide (mmol/liter) 22 23   23
Urea nitrogen (mg/dl)  14 11   11
Creatinine (mg/dl)  1.0 0.8   0.62
Glucose (mg/dl)  126 101   96
Calcium (mg/dl)   8.1 8.0   8.1
Total protein (g/dl)  5.3 5.4 6. .3 5.2
Albumin (g/dl)  2.4 2.4   2.2
Alanine aminotransferase (U/liter)   32 17   38
Aspartate aminotransferase (U/liter)  7 19 12   30
Alkaline phosphatase (U/liter) 40–129 62 53   68
Total bilirubin (mg/dl)  0.3 0.2  0.2
Serum osmolality (mOsm/kg) 285–295 272 263 28 90 268
Lactate (mmol/liter) 0.5–1.9 1.9   1.2
Iron (μg/dl) 45–160 37 30–160 36
Total iron-binding capacity (μg/dl) 228–428 205 23 4 105
Ferritin (ng/ml) 50 82  130
Erythrocyte sedimentation rate (mm/hr)   7
C-reactive protein (mg/liter)   59.2
Fecal calprotectin (μg/g) 1038.8",Strongyloidiasis with human T-lymphotropic virus type 1 infection,Strongyloidiasis with hyperinfection syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 44-year-old man was evaluated at this hospital because of diarrhea, weight loss, and abdominal pain.
Approximately 6 months before admission, the patient began to have early satiety, nausea approximately 30 minutes after eating small amounts of food, and intermittent anorexia. He began to consume primarily liquids for breakfast and lunch and would skip dinner; during the next 5 months, he lost 9 kg.
One month before admission, the patient was admitted to another hospital because of fever, malaise, neck pain, photophobia, retro-orbital pain, and headache. The temperature was 38.5[degrees]C, the heart rate 118 beats per minute, and the blood pressure 94/72 mm Hg. The white-cell count was 28,600 per microliter (reference range, 4500 to 10,800); other laboratory test results are shown in Table 1. Blood samples were obtained for culture. Computed tomography (CT) of the head, performed after the administration of intravenous contrast material, was reportedly normal. Empirical vancomycin, ceftriaxone, acyclovir, and dexamethasone were administered intravenously. A lumbar puncture (opening pressure not recorded) revealed cloudy cerebrospinal fluid (CSF) with 4 red cells per microliter and 1306 white cells per microliter, of which 83% were neutrophils (reference value, <25%), 12% were monocytes, and 5% were lymphocytes. Gram's staining of the CSF revealed no organisms; the CSF protein level was 98 mg per deciliter (reference range, 15 to 45) and the glucose level was 68 mg per deciliter (3.8 mmol per liter; reference range, 35 to 65 mg per deciliter [1.9 to 3.6 mmol per liter]).	
Table 1 
On the third day at the other hospital, dysuria, nausea, and episodes of hemoptysis and diarrhea developed. CT of the chest and abdomen was performed after the administration of intravenous contrast material; the results were reportedly unremarkable. On the fifth hospital day, after CSF culture revealed no growth and polymerase-chain-reaction (PCR) testing for herpes simplex virus types 1 and 2 was negative, antimicrobial and glucocorticoid therapies were discontinued and the patient was discharged home. The vitamin B12 level and results of serum protein electrophoresis were normal; other laboratory test results obtained the day before discharge are shown in Table 1.
After the patient's discharge from the other hospital, new, near-constant epigastric pain developed. Approximately 1 hour after meals, nausea and vomiting occurred, with diffuse abdominal bloating and cramping. In addition, watery diarrhea began to occur twice daily, without hematochezia or melena. One week after discharge, the patient's primary care physician prescribed omeprazole. The patient lost an additional 14 kg. Approximately 3 weeks later, he presented to the emergency department of this hospital for evaluation.
The patient's medical history was notable for depression, lumbar pain, and vitamin D deficiency. Intermittent diffuse headache persisted in the 3 weeks after discharge from the other hospital, and the patient reported low-grade fever. A review of systems was negative for night sweats, chills, neck pain, photophobia, vision changes, chest pain, dyspnea, cough, coryza, sore throat, oral ulcers, back pain, dysuria, hematuria, rashes, joint or muscle pain, edema, and pruritus. Medications included venlafaxine, cholecalciferol, and omeprazole. The patient took an herbal supplement of unknown type in the week after discharge from the other hospital. He had never used nonsteroidal antiinflammatory drugs. He had no known medication allergies.
The patient grew up on an island in the Caribbean and had immigrated to the United States 10 years earlier; he had last returned to the Caribbean 4 months before admission. He had traveled extensively in the northeastern and Mountain West regions of the United States. He was married with one child but had no known sick contacts. He drank one beer per day and had never smoked cigarettes; he occasionally smoked marijuana. There was no family history of gastrointestinal infections, gastrointestinal cancers (his mother had ovarian cancer), peptic-ulcer disease, pancreatitis, irritable bowel syndrome, inflammatory bowel disease, autoimmune conditions, or malabsorption syndromes.
The temperature was 37.2[degrees]C, the heart rate 107 beats per minute, the blood pressure 101/57 mm Hg, and the oxygen saturation 99% while the patient was breathing ambient air; the body-mass index (the weight in kilograms divided by the square of the height in meters) was 18.6. Examination was notable for cachexia. The abdomen was soft and nondistended, with no organomegaly. There was mild epigastric tenderness, without rebound or guarding. No rashes, skin ulcerations, or lymphadenopathy were noted. The remainder of the examination was normal.
The international normalized ratio and blood levels of magnesium, phosphorus, lipase, vitamin B12, folate, globulin, and IgA were normal, as were the results of a urinalysis; other laboratory test results are shown in Table 1. An electrocardiogram showed right bundle-branch block, with no evidence of ischemia.
Dr. Theodore T. Pierce: A CT scan of the abdomen and pelvis (Figure 1), obtained after the administration of intravenous contrast material, showed diffuse mild distention of the large and small bowel without a transition point to indicate a bowel obstruction. The presence of diffuse mild thickening of the bowel wall, mural enhancement, and prominent mesenteric vessels suggested diffuse inflammation. Additional nonspecific findings included a reduced number of jejunal folds and an increased number of ileal folds (collectively known as jejunoileal fold pattern reversal) as well as mesenteric lymphadenopathy.	
Figure 1 
Dr. Chu: Normal saline was administered intravenously, and sucralfate and dicyclomine were given orally. The patient was admitted to this hospital.
Diarrhea and abdominal pain persisted on the second hospital day. Tests for human immunodeficiency virus (HIV) type 1 and type 2 antibodies and antigen, Treponema pallidum antibodies, Clostridium difficile antigen, and tissue transglutaminase IgA were negative. Blood testing for Helicobacter pylori IgG was positive; however, a stool test for H. pylori antigen was negative.
Additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 44-year-old man was evaluated at this hospital because of diarrhea, weight loss, and abdominal pain.
Approximately 6 months before admission, the patient began to have early satiety, nausea approximately 30 minutes after eating small amounts of food, and intermittent anorexia. He began to consume primarily liquids for breakfast and lunch and would skip dinner; during the next 5 months, he lost 9 kg.
One month before admission, the patient was admitted to another hospital because of fever, malaise, neck pain, photophobia, retro-orbital pain, and headache. The temperature was 38.5[degrees]C, the heart rate 118 beats per minute, and the blood pressure 94/72 mm Hg. The white-cell count was 28,600 per microliter (reference range, 4500 to 10,800); other laboratory test results are shown in Table 1. Blood samples were obtained for culture. Computed tomography (CT) of the head, performed after the administration of intravenous contrast material, was reportedly normal. Empirical vancomycin, ceftriaxone, acyclovir, and dexamethasone were administered intravenously. A lumbar puncture (opening pressure not recorded) revealed cloudy cerebrospinal fluid (CSF) with 4 red cells per microliter and 1306 white cells per microliter, of which 83% were neutrophils (reference value, <25%), 12% were monocytes, and 5% were lymphocytes. Gram's staining of the CSF revealed no organisms; the CSF protein level was 98 mg per deciliter (reference range, 15 to 45) and the glucose level was 68 mg per deciliter (3.8 mmol per liter; reference range, 35 to 65 mg per deciliter [1.9 to 3.6 mmol per liter]).	
Table 1 
On the third day at the other hospital, dysuria, nausea, and episodes of hemoptysis and diarrhea developed. CT of the chest and abdomen was performed after the administration of intravenous contrast material; the results were reportedly unremarkable. On the fifth hospital day, after CSF culture revealed no growth and polymerase-chain-reaction (PCR) testing for herpes simplex virus types 1 and 2 was negative, antimicrobial and glucocorticoid therapies were discontinued and the patient was discharged home. The vitamin B12 level and results of serum protein electrophoresis were normal; other laboratory test results obtained the day before discharge are shown in Table 1.
After the patient's discharge from the other hospital, new, near-constant epigastric pain developed. Approximately 1 hour after meals, nausea and vomiting occurred, with diffuse abdominal bloating and cramping. In addition, watery diarrhea began to occur twice daily, without hematochezia or melena. One week after discharge, the patient's primary care physician prescribed omeprazole. The patient lost an additional 14 kg. Approximately 3 weeks later, he presented to the emergency department of this hospital for evaluation.
The patient's medical history was notable for depression, lumbar pain, and vitamin D deficiency. Intermittent diffuse headache persisted in the 3 weeks after discharge from the other hospital, and the patient reported low-grade fever. A review of systems was negative for night sweats, chills, neck pain, photophobia, vision changes, chest pain, dyspnea, cough, coryza, sore throat, oral ulcers, back pain, dysuria, hematuria, rashes, joint or muscle pain, edema, and pruritus. Medications included venlafaxine, cholecalciferol, and omeprazole. The patient took an herbal supplement of unknown type in the week after discharge from the other hospital. He had never used nonsteroidal antiinflammatory drugs. He had no known medication allergies.
The patient grew up on an island in the Caribbean and had immigrated to the United States 10 years earlier; he had last returned to the Caribbean 4 months before admission. He had traveled extensively in the northeastern and Mountain West regions of the United States. He was married with one child but had no known sick contacts. He drank one beer per day and had never smoked cigarettes; he occasionally smoked marijuana. There was no family history of gastrointestinal infections, gastrointestinal cancers (his mother had ovarian cancer), peptic-ulcer disease, pancreatitis, irritable bowel syndrome, inflammatory bowel disease, autoimmune conditions, or malabsorption syndromes.
The temperature was 37.2[degrees]C, the heart rate 107 beats per minute, the blood pressure 101/57 mm Hg, and the oxygen saturation 99% while the patient was breathing ambient air; the body-mass index (the weight in kilograms divided by the square of the height in meters) was 18.6. Examination was notable for cachexia. The abdomen was soft and nondistended, with no organomegaly. There was mild epigastric tenderness, without rebound or guarding. No rashes, skin ulcerations, or lymphadenopathy were noted. The remainder of the examination was normal.
The international normalized ratio and blood levels of magnesium, phosphorus, lipase, vitamin B12, folate, globulin, and IgA were normal, as were the results of a urinalysis; other laboratory test results are shown in Table 1. An electrocardiogram showed right bundle-branch block, with no evidence of ischemia.
Dr. Theodore T. Pierce: A CT scan of the abdomen and pelvis (Figure 1), obtained after the administration of intravenous contrast material, showed diffuse mild distention of the large and small bowel without a transition point to indicate a bowel obstruction. The presence of diffuse mild thickening of the bowel wall, mural enhancement, and prominent mesenteric vessels suggested diffuse inflammation. Additional nonspecific findings included a reduced number of jejunal folds and an increased number of ileal folds (collectively known as jejunoileal fold pattern reversal) as well as mesenteric lymphadenopathy.	
Figure 1 
Dr. Chu: Normal saline was administered intravenously, and sucralfate and dicyclomine were given orally. The patient was admitted to this hospital.
Diarrhea and abdominal pain persisted on the second hospital day. Tests for human immunodeficiency virus (HIV) type 1 and type 2 antibodies and antigen, Treponema pallidum antibodies, Clostridium difficile antigen, and tissue transglutaminase IgA were negative. Blood testing for Helicobacter pylori IgG was positive; however, a stool test for H. pylori antigen was negative.
Additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Whipple's disease. The patient's symptoms of weight loss, diarrhea, and abdominal pain, along with the presence of fever and neurological symptoms, suggest a systemic disease. The patient's history of travel to the Caribbean and the northeastern and Mountain West regions of the United States raises the possibility of an infectious disease. The patient's cerebrospinal fluid (CSF) findings of elevated protein and white blood cell count, predominantly neutrophils, suggest an infectious process, but the negative Gram stain and culture make bacterial meningitis unlikely. The patient's gastrointestinal symptoms, along with the CT findings of diffuse bowel wall thickening and mesenteric lymphadenopathy, suggest a gastrointestinal disease. The negative tests for HIV, Treponema pallidum, Clostridium difficile, and tissue transglutaminase IgA rule out some common causes of these symptoms. The positive blood test for Helicobacter pylori IgG suggests past exposure but the negative stool test for H. pylori antigen makes active infection unlikely. The combination of gastrointestinal and neurological symptoms, along with the patient's travel history, makes Whipple's disease a likely diagnosis. This is a rare systemic infectious disease caused by the bacterium Tropheryma whipplei, which can affect many parts of the body, including the gastrointestinal tract and the central nervous system.""
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        ""content"": ""The patient's symptoms of diarrhea, weight loss, abdominal pain, early satiety, nausea, and anorexia, along with the CT scan findings of diffuse inflammation and mesenteric lymphadenopathy, suggest a gastrointestinal disorder. The patient's history of travel to the Caribbean and the presence of fever and malaise could suggest an infectious cause, but tests for common infectious agents were negative. The patient's symptoms did not improve with omeprazole, suggesting that this is not a simple case of gastritis or peptic ulcer disease. The presence of cachexia and significant weight loss could suggest a malignancy, but there is no mention of any masses or lesions on imaging. The patient's symptoms and imaging findings are consistent with a malabsorption syndrome, such as Whipple's disease. Whipple's disease is a rare bacterial infection that most commonly affects the small intestine and can cause malabsorption, leading to symptoms such as diarrhea and weight loss. It can also cause systemic symptoms such as fever and malaise.\n\nDiagnosis: Whipple's disease.""
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        ""content"": ""The patient is a 44-year-old man presenting with diarrhea, weight loss, and abdominal pain. He also has a history of fever, malaise, neck pain, photophobia, retro-orbital pain, and headache. His symptoms began with early satiety, nausea, and intermittent anorexia, leading to significant weight loss. He also had a period of hospitalization due to fever and other symptoms, during which he was treated with antibiotics and glucocorticoids. After discharge, he developed constant epigastric pain, nausea, vomiting, abdominal bloating and cramping, and watery diarrhea. His medical history includes depression, lumbar pain, and vitamin D deficiency. He has a history of travel and immigrated from the Caribbean 10 years ago. \n\nThe differential diagnosis for this patient includes gastrointestinal infections, gastrointestinal cancers, peptic-ulcer disease, pancreatitis, irritable bowel syndrome, inflammatory bowel disease, autoimmune conditions, or malabsorption syndromes. Given his travel history, tropical sprue could also be considered. \n\nHis lab results show a high white blood cell count, suggesting an infection or inflammation. His CSF analysis also showed a high white cell count, suggesting a possible central nervous system infection, although no organisms were found on Gram stain and his CSF culture showed no growth. His CT scan showed diffuse mild distention of the large and small bowel, suggesting inflammation. \n\nHis tests for HIV, Treponema pallidum, Clostridium difficile, and tissue transglutaminase IgA were all negative, ruling out HIV, syphilis, C. difficile infection, and celiac disease. His blood test for Helicobacter pylori IgG was positive, but his stool test for H. pylori antigen was negative, suggesting a past but not current H. pylori infection.\n\nGiven his symptoms, lab results, and imaging findings, the most likely diagnosis is a form of inflammatory bowel disease. His symptoms of diarrhea, abdominal pain, and weight loss, along with his imaging findings of bowel inflammation, are consistent with this diagnosis. His negative tests for infectious causes and celiac disease further support this diagnosis.\n\nDiagnosis: Inflammatory Bowel Disease.""
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10.1056/NEJMcpc1913468,Case 2-2020: A 64-Year-Old Man with Fever and Respiratory Failure,"Hemoglobin (g/dl)   13.8 11.7 10.4
Hematocrit (%)   43.2 34.1 30.2
Platelet count (per μl)   256,000 128,000 119,000
White-cell count (per μl)   11,820 6850 2760
Differential count (%)
Neutrophils   54.2 61.6 97.3
Lymphocytes   25.4 23.6 0.9
Monocytes   10.7 8.3
Eosinophils   8.4 5.1 0.9
Basophils   0.7 1.0
Plasma cells (%) 0 0.9
Erythrocyte sedimentation rate (mm/hr)   65 31 41
C-reactive protein (mg/liter)  .0 115.8 8.8 287.5
Creatinine (mg/dl)   1.07 5.78 4.51
Urea nitrogen (mg/dl)   22 80 56
N-terminal pro–B-type natriuretic peptide (pg/ml)   4842 46,830
Lactate (mmol/liter)   3.2",Disseminated coccidioidomycosis and ANCA associated glomeruloneph,Disseminated coccidioidomycosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old man was admitted to this hospital in the spring because of acute renal failure.
The patient had been generally well until 4.5 months before this admission, when fevers, malaise, mild cough, and pain in the left flank developed. He was evaluated at an outside urgent care clinic, where chest radiography was reportedly normal. A clinical diagnosis of sinusitis was made, and amoxicillin-clavulanic acid was prescribed. When symptoms did not abate, doxycycline was prescribed. The flank pain was attributed to muscular strain, and a short course of prednisone and cyclobenzaprine was administered.
Four months before this admission, a fever with a temperature of up to 38.9[degrees]C and worsening cough developed. The patient was evaluated in an urgent care clinic at this hospital. On examination, the temperature was 36.6[degrees]C, the heart rate 58 beats per minute, the blood pressure 125/71 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. Auscultation of the lungs revealed crackles in the left lower lung field; the remainder of the examination was normal. Blood levels of electrolytes and glucose were normal; other laboratory test results are shown in Table 1. Chest radiography revealed faint air-space opacities in the left lower lobe and left perihilar region, and amoxicillin-clavulanic acid was prescribed for empirical treatment of pneumonia.	
Table 1
Dr. Victorine V. Muse: Two months before this admission, repeat chest radiography revealed persistence of the air-space opacity in the left perihilar region. Three weeks later, computed tomography (CT) of the chest, abdomen, and pelvis was performed after the administration of intravenous contrast material. Because of a known allergy to intravenous contrast material, prednisone and diphenhydramine were administered prophylactically. The images showed centrilobular nodules and patchy opacities in both lung bases, as well as mediastinal and left hilar lymphadenopathy (Figure 1A and 1B).	
Figure 1 
Dr. Niccum: Two days later, early satiety, nausea, and nonbloody diarrhea developed, along with orthopnea, edema in the legs, abdominal distention, decreased urine output, and weight gain. Symptoms progressed during the subsequent 3 weeks. Routine laboratory testing revealed a creatinine level of 5.78 mg per deciliter (511 mmol per liter) (normal range, 0.60 to 1.50 mg per deciliter [53 to 133 mmol per liter]) and a blood urea nitrogen level of 80 mg per deciliter (29 mmol per liter) (normal range, 8 to 25 mg per deciliter [3 to 9 mmol per liter]). The patient was referred to the emergency department at this hospital for management of acute renal failure.
The patient had a history of congenital aortic stenosis due to a subaortic membrane, hypertrophic cardiomyopathy, atrial fibrillation, complete heart block, ascending aortic aneurysm with severe aortic insufficiency, diverticulosis, and gout. He had undergone a subaortic membrane resection when he was 10 years of age and an open revision surgery with aortic-valve repair and septal myomectomy when he was 50 years of age. When he was 52 years of age, a permanent pacemaker was placed after complete heart block had developed. He had undergone pulmonary-vein isolation when he was 58 years of age. Medications were rivaroxaban, sotalol, eplerenone, furosemide, simvastatin, potassium chloride, allopurinol, and ibuprofen. Known medication allergies included intravenous iodinated contrast material, which caused hives.
The patient lived with his wife in a suburban community in New England and had recently retired from a career in the information technology industry. He had traveled to Ventura County in California the preceding autumn, as well as to Europe and to the southeastern United States several years earlier. He had a 20-pack-year history of cigarette smoking and had quit smoking 9 years earlier. He drank alcohol socially and had never used illicit drugs. His mother had congestive heart failure and his father had peripheral vascular disease. His nephew had a thoracic aortic aneurysm, and his brother had died from a ruptured thoracic aortic aneurysm.
On examination, the patient appeared well and was not in acute distress. The temperature was 36.5[degrees]C, the pulse 60 beats per minute, the blood pressure 135/60 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 95% while he was breathing ambient air. The heart sounds were regular, and a systolic murmur (2/6) was present at the right upper sternal border. There was edema in the legs. The remainder of the examination was normal; specifically, there were no ulcerations noted on the skin or oropharynx, and he had no rashes. Urinalysis revealed 3+ blood and 2+ protein, and microscopic examination of the sediment revealed 10 to 20 red cells per high-power field, including acanthocytes. Results of kidney function tests were unchanged from those obtained earlier that day; results of additional laboratory tests are shown in Table 1. Ultrasonography of the kidneys and bladder revealed echogenic kidneys but no evidence of hydronephrosis. Intravenous methylprednisolone was initiated empirically for the treatment of rapidly progressive glomerulonephritis, and the patient was admitted to this hospital.
The next day, additional laboratory test results were received. Tests for hepatitis B core antibody, hepatitis C antibody, human immunodeficiency virus (HIV) type 1 p24 antigen, and antibodies to HIV types 1 and 2 were negative. An assay for antinuclear antibodies was positive at 1:40 with a speckled pattern; cryoglobulins and antibodies to the Goodpasture antigen were not detected. Blood levels of C3 and C4 were normal. Urine tests for Bence Jones protein were negative, and results of serum protein electrophoresis were normal. A test for antineutrophil cytoplasmic antibodies (ANCAs) was positive, with a perinuclear staining pattern, and an enzyme-linked immunosorbent assay confirmed the presence of myeloperoxidase ANCA at a titer of 743 U (reference range, <2.8). Oral cyclophosphamide therapy was begun.
On hospital day 3, a central venous catheter was placed, and therapeutic plasma exchange was initiated; intravenous methylprednisolone treatment was discontinued, and administration of high-dose oral prednisone was begun. On hospital day 6, intravenous rituximab was administered. On hospital day 7, intermittent hemodialysis was initiated owing to persistent uremia and acidosis.
On hospital day 14, a fever with a temperature of up to 38.4[degrees]C developed, along with a mild cough and sore throat. Urinalysis revealed a specific gravity of 1.010 and 2+ bacteria; nitrites and leukocyte esterase were not detected. On hospital day 16, the urine culture grew abundant Enterobacter cloacae, and intravenous cefepime treatment was initiated. After seven sessions of therapeutic plasma exchange and administration of two rituximab infusions, the patient was discharged home. Prednisone (40 mg daily), cyclophosphamide, and ciprofloxacin were prescribed.
After discharge, a fever with a temperature of up to 38.9[degrees]C persisted, as did fatigue, malaise, and watery diarrhea. The patient also reported the development of painful oral ulcers. Two days after discharge, dyspnea on exertion developed, along with productive cough, and the patient returned to the emergency department at this hospital.
On arrival, the patient appeared ill and in respiratory distress. The temperature was 36.1[degrees]C, the pulse 104 beats per minute, the blood pressure 140/70 mm Hg, the respiratory rate 54 breaths per minute, and the oxygen saturation 93% while he was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. Examination revealed numerous shallow ulcerations on the tongue and lips, diffuse wheezing with inspiratory crackles, and marked edema in the legs; the remainder of the examination was unchanged. Laboratory test results are shown in Table 1. Cytomegalovirus DNA was detected in the blood (4680 international units [IU] per milliliter). Blood samples were obtained for culture. The patient was readmitted to this hospital.
Dr. Muse: Radiography of the chest revealed pulmonary interstitial edema with patchy opacities in the left retrocardiac region. CT of the chest revealed diffuse ground-glass opacities with intralobular septal thickening and worsening mediastinal and hilar lymphadenopathy (Figure 1C and 1D).
Dr. Niccum: Intravenous cefepime, vancomycin, and azithromycin were administered empirically. The next day, hemodialysis was performed, and 4 liters of fluid were removed by ultrafiltration for the management of congestive heart failure. During the last hour of the dialysis session, the dyspnea began to worsen and hypoxemia developed; supplemental oxygen was administered through a nonrebreather face mask. Ipratropium-albuterol nebulizers were administered, and the patient was transferred to the intensive care unit for management of hypoxemic respiratory failure.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old man was admitted to this hospital in the spring because of acute renal failure.
The patient had been generally well until 4.5 months before this admission, when fevers, malaise, mild cough, and pain in the left flank developed. He was evaluated at an outside urgent care clinic, where chest radiography was reportedly normal. A clinical diagnosis of sinusitis was made, and amoxicillin-clavulanic acid was prescribed. When symptoms did not abate, doxycycline was prescribed. The flank pain was attributed to muscular strain, and a short course of prednisone and cyclobenzaprine was administered.
Four months before this admission, a fever with a temperature of up to 38.9[degrees]C and worsening cough developed. The patient was evaluated in an urgent care clinic at this hospital. On examination, the temperature was 36.6[degrees]C, the heart rate 58 beats per minute, the blood pressure 125/71 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. Auscultation of the lungs revealed crackles in the left lower lung field; the remainder of the examination was normal. Blood levels of electrolytes and glucose were normal; other laboratory test results are shown in Table 1. Chest radiography revealed faint air-space opacities in the left lower lobe and left perihilar region, and amoxicillin-clavulanic acid was prescribed for empirical treatment of pneumonia.	
Table 1
Dr. Victorine V. Muse: Two months before this admission, repeat chest radiography revealed persistence of the air-space opacity in the left perihilar region. Three weeks later, computed tomography (CT) of the chest, abdomen, and pelvis was performed after the administration of intravenous contrast material. Because of a known allergy to intravenous contrast material, prednisone and diphenhydramine were administered prophylactically. The images showed centrilobular nodules and patchy opacities in both lung bases, as well as mediastinal and left hilar lymphadenopathy (Figure 1A and 1B).	
Figure 1 
Dr. Niccum: Two days later, early satiety, nausea, and nonbloody diarrhea developed, along with orthopnea, edema in the legs, abdominal distention, decreased urine output, and weight gain. Symptoms progressed during the subsequent 3 weeks. Routine laboratory testing revealed a creatinine level of 5.78 mg per deciliter (511 mmol per liter) (normal range, 0.60 to 1.50 mg per deciliter [53 to 133 mmol per liter]) and a blood urea nitrogen level of 80 mg per deciliter (29 mmol per liter) (normal range, 8 to 25 mg per deciliter [3 to 9 mmol per liter]). The patient was referred to the emergency department at this hospital for management of acute renal failure.
The patient had a history of congenital aortic stenosis due to a subaortic membrane, hypertrophic cardiomyopathy, atrial fibrillation, complete heart block, ascending aortic aneurysm with severe aortic insufficiency, diverticulosis, and gout. He had undergone a subaortic membrane resection when he was 10 years of age and an open revision surgery with aortic-valve repair and septal myomectomy when he was 50 years of age. When he was 52 years of age, a permanent pacemaker was placed after complete heart block had developed. He had undergone pulmonary-vein isolation when he was 58 years of age. Medications were rivaroxaban, sotalol, eplerenone, furosemide, simvastatin, potassium chloride, allopurinol, and ibuprofen. Known medication allergies included intravenous iodinated contrast material, which caused hives.
The patient lived with his wife in a suburban community in New England and had recently retired from a career in the information technology industry. He had traveled to Ventura County in California the preceding autumn, as well as to Europe and to the southeastern United States several years earlier. He had a 20-pack-year history of cigarette smoking and had quit smoking 9 years earlier. He drank alcohol socially and had never used illicit drugs. His mother had congestive heart failure and his father had peripheral vascular disease. His nephew had a thoracic aortic aneurysm, and his brother had died from a ruptured thoracic aortic aneurysm.
On examination, the patient appeared well and was not in acute distress. The temperature was 36.5[degrees]C, the pulse 60 beats per minute, the blood pressure 135/60 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 95% while he was breathing ambient air. The heart sounds were regular, and a systolic murmur (2/6) was present at the right upper sternal border. There was edema in the legs. The remainder of the examination was normal; specifically, there were no ulcerations noted on the skin or oropharynx, and he had no rashes. Urinalysis revealed 3+ blood and 2+ protein, and microscopic examination of the sediment revealed 10 to 20 red cells per high-power field, including acanthocytes. Results of kidney function tests were unchanged from those obtained earlier that day; results of additional laboratory tests are shown in Table 1. Ultrasonography of the kidneys and bladder revealed echogenic kidneys but no evidence of hydronephrosis. Intravenous methylprednisolone was initiated empirically for the treatment of rapidly progressive glomerulonephritis, and the patient was admitted to this hospital.
The next day, additional laboratory test results were received. Tests for hepatitis B core antibody, hepatitis C antibody, human immunodeficiency virus (HIV) type 1 p24 antigen, and antibodies to HIV types 1 and 2 were negative. An assay for antinuclear antibodies was positive at 1:40 with a speckled pattern; cryoglobulins and antibodies to the Goodpasture antigen were not detected. Blood levels of C3 and C4 were normal. Urine tests for Bence Jones protein were negative, and results of serum protein electrophoresis were normal. A test for antineutrophil cytoplasmic antibodies (ANCAs) was positive, with a perinuclear staining pattern, and an enzyme-linked immunosorbent assay confirmed the presence of myeloperoxidase ANCA at a titer of 743 U (reference range, <2.8). Oral cyclophosphamide therapy was begun.
On hospital day 3, a central venous catheter was placed, and therapeutic plasma exchange was initiated; intravenous methylprednisolone treatment was discontinued, and administration of high-dose oral prednisone was begun. On hospital day 6, intravenous rituximab was administered. On hospital day 7, intermittent hemodialysis was initiated owing to persistent uremia and acidosis.
On hospital day 14, a fever with a temperature of up to 38.4[degrees]C developed, along with a mild cough and sore throat. Urinalysis revealed a specific gravity of 1.010 and 2+ bacteria; nitrites and leukocyte esterase were not detected. On hospital day 16, the urine culture grew abundant Enterobacter cloacae, and intravenous cefepime treatment was initiated. After seven sessions of therapeutic plasma exchange and administration of two rituximab infusions, the patient was discharged home. Prednisone (40 mg daily), cyclophosphamide, and ciprofloxacin were prescribed.
After discharge, a fever with a temperature of up to 38.9[degrees]C persisted, as did fatigue, malaise, and watery diarrhea. The patient also reported the development of painful oral ulcers. Two days after discharge, dyspnea on exertion developed, along with productive cough, and the patient returned to the emergency department at this hospital.
On arrival, the patient appeared ill and in respiratory distress. The temperature was 36.1[degrees]C, the pulse 104 beats per minute, the blood pressure 140/70 mm Hg, the respiratory rate 54 breaths per minute, and the oxygen saturation 93% while he was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. Examination revealed numerous shallow ulcerations on the tongue and lips, diffuse wheezing with inspiratory crackles, and marked edema in the legs; the remainder of the examination was unchanged. Laboratory test results are shown in Table 1. Cytomegalovirus DNA was detected in the blood (4680 international units [IU] per milliliter). Blood samples were obtained for culture. The patient was readmitted to this hospital.
Dr. Muse: Radiography of the chest revealed pulmonary interstitial edema with patchy opacities in the left retrocardiac region. CT of the chest revealed diffuse ground-glass opacities with intralobular septal thickening and worsening mediastinal and hilar lymphadenopathy (Figure 1C and 1D).
Dr. Niccum: Intravenous cefepime, vancomycin, and azithromycin were administered empirically. The next day, hemodialysis was performed, and 4 liters of fluid were removed by ultrafiltration for the management of congestive heart failure. During the last hour of the dialysis session, the dyspnea began to worsen and hypoxemia developed; supplemental oxygen was administered through a nonrebreather face mask. Ipratropium-albuterol nebulizers were administered, and the patient was transferred to the intensive care unit for management of hypoxemic respiratory failure.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fever, cough, and flank pain, along with the presence of centrilobular nodules and patchy opacities in both lung bases, and mediastinal and left hilar lymphadenopathy on CT scan, suggest an infectious or inflammatory process. The development of acute renal failure, presence of blood and protein in the urine, and the presence of myeloperoxidase ANCA at a high titer suggest an autoimmune process affecting the kidneys. The combination of lung and kidney involvement, along with the presence of ANCA, is suggestive of ANCA-associated vasculitis, specifically microscopic polyangiitis or granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis). The absence of sinus involvement or granulomas on imaging makes granulomatosis with polyangiitis less likely. Therefore, the most likely diagnosis is microscopic polyangiitis. \n\nDiagnosis: Microscopic polyangiitis.""
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        ""content"": ""The patient is a 64-year-old man with a history of congenital aortic stenosis, hypertrophic cardiomyopathy, atrial fibrillation, complete heart block, ascending aortic aneurysm with severe aortic insufficiency, diverticulosis, and gout. He presents with acute renal failure, fevers, malaise, mild cough, and pain in the left flank. His symptoms did not improve with antibiotics, and he later developed worsening cough, fever, early satiety, nausea, nonbloody diarrhea, orthopnea, edema in the legs, abdominal distention, decreased urine output, and weight gain. His creatinine and blood urea nitrogen levels were elevated. His urinalysis revealed blood and protein, and microscopic examination of the sediment revealed red cells, including acanthocytes. His chest radiography revealed faint air-space opacities in the left lower lobe and left perihilar region, and CT of the chest showed centrilobular nodules and patchy opacities in both lung bases, as well as mediastinal and left hilar lymphadenopathy. His test for antineutrophil cytoplasmic antibodies (ANCAs) was positive, with a perinuclear staining pattern, and an enzyme-linked immunosorbent assay confirmed the presence of myeloperoxidase ANCA at a high titer. \n\nThe differential diagnosis for this patient includes Goodpasture syndrome, Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Goodpasture syndrome is less likely because the patient's antibodies to the Goodpasture antigen were not detected. Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome are all forms of ANCA-associated vasculitis, which can cause rapidly progressive glomerulonephritis and lung involvement. However, Wegener's granulomatosis is typically associated with c-ANCA and PR3-ANCA, not p-ANCA and MPO-ANCA, which were found in this patient. Churg-Strauss syndrome is less likely because the patient does not have a history of asthma or eosinophilia. Therefore, the most likely diagnosis is microscopic polyangiitis, which is associated with p-ANCA and MPO-ANCA and can cause rapidly progressive glomerulonephritis and lung involvement.\n\nDiagnosis: Microscopic polyangiitis.""
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10.1056/NEJMcpc1913469,Case 1-2020: An 11-Year-Old Boy with Vomiting and Weight Loss,"Hemoglobin (g/dl)  15.7
Hematocrit (%)  43.9
White-cell count (per μl) 450 ,500 10,050
Differential count (%)
Neutrophils 52.9
Immature granulocytes 0.0–0.3 0.3                            
Lymphocytes 37.9
Monocytes   6.8
Eosinophils   1.5
Basophils   0.6
Red-cell count (per μl) 4,000,000–5,200,000 5,410,000
Mean corpuscular volume (fl)  81.1
Mean corpuscular hemoglobin (pg) 25. 3.0 29.0
Mean corpuscular hemoglobin concen‚Äë
tration (g/dl)
31. 7.0 35.8
Red-cell distribution width (%)   11.6
Platelet count (per μl)   434,000
Erythrocyte sedimentation rate (mm/hr)   12
Sodium (mmol/liter)   132 138 128
Potassium (mmol/liter)   4.7 5.1 4.3
Chloride (mmol/liter)   91 95 88
Carbon dioxide (mmol/liter)   20 21 19
Anion gap (mmol/liter)   21 22 21
Calcium (mg/dl)   10.5 10.5 10.6
Phosphorus (mg/dl) 4.7 4.9
Magnesium (mg/dl)   1.9 2.1
Urea nitrogen (mg/dl)  30 22 29
Creatinine (mg/dl)   0.70 0.68 0.86
Glucose (mg/dl)   88 98 94
Protein (g/dl)
Total 6. .3 8.2
Albumin   5.1
Globulin   3.1
Alanine aminotransferase (U/liter)   29
Aspartate aminotransferase (U/liter)   34
Alkaline phosphatase (U/liter) 247
Bilirubin (mg/dl)
Total 0.4
Direct  <0.2
Thyrotropin (μIU/ml) 0.4 0 7.87                                                                           Triglycerides (mg/dl)   35
Cholesterol (mg/dl)  132
High-density lipoprotein (mg/dl)   57
Low-density lipoprotein (mg/dl)   68
Iron (μg/dl) 45–160 127
Total iron-binding capacity (μg/dl) 23 4 387
Ferritin (μg/liter) 2 00 393
Transferrin saturation (%) 33
C-reactive protein (mg/liter)  .0 2.2","Autoimmune primary adrenal insufficiency and 
celiac disease",Celiac disease and adrenal insufficiency.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 11-year-old boy was seen in the emergency department of this hospital because of ongoing vomiting and weight loss.
One month before this presentation, the patient was evaluated by his primary care pediatrician because of nausea, vomiting, decreased appetite, and weight loss. The patient and his parents reported that these symptoms had begun approximately 3 months earlier and had worsened during the past 3 weeks. The nausea and vomiting occurred in the early morning, abated later in the day, and were exacerbated by stress. The patient also reported fatigue and an intermittent sensation of regurgitation and burning in the throat. He had begun treatment with lansoprazole 5 days earlier, with no decrease in symptoms. On examination, the weight was 36.4 kg (37th percentile) and the height was 148.6 cm (58th percentile); at a visit to the primary care clinic 11 months earlier, the weight had been 40.5 kg (78th percentile) and the height had been 143.5 cm (62nd percentile). The abdomen was soft, with normal bowel sounds and without tenderness or masses. The remainder of the examination was normal. Laboratory test results are shown in Table 1. Omeprazole was prescribed, and the patient was referred to a pediatric gastroenterologist and a pediatric psychologist at this hospital.	
Table 1
On presentation to the pediatric gastroenterology clinic of this hospital (3 weeks before this presentation), the patient reported that the nausea and vomiting had decreased slightly after he had begun treatment with omeprazole, and then the symptoms had worsened. The vomitus was nonbloody and nonbilious. He had normal bowel movements, without blood, two or three times each day.
The patient was a twin and had been born by cesarean section at 36 weeks of gestation. During infancy, he had had gastroesophageal reflux disease (GERD) that was treated with ranitidine, omeprazole, and lansoprazole. He had been admitted to a local hospital because of bronchiolitis at 15 months of age, after which he had occasional episodes of wheezing.
When the patient was 5 years of age, decreased appetite, weight loss, and episodes of vomiting preceded by sore throat developed, and he was evaluated by a pediatric gastroenterologist at another hospital. At that time, an upper gastrointestinal series, performed after the administration of barium contrast, was normal. Tests for IgA and tissue transglutaminase IgA and IgG were negative. Lansoprazole and an antireflux diet were prescribed, and the symptoms resolved over a period of approximately 2 months, after which the proton-pump inhibitor was discontinued.
When the patient was 6 years of age, he was referred to a pediatric nephrologist at the other hospital because of hypertension. Renal ultrasonography was normal, and the results of ambulatory blood-pressure monitoring suggested the ""white coat"" effect (i.e., blood pressure elevated only in a clinical setting). The patient also had seasonal allergies, red-green color blindness, and a history of speech delay and retractile testes.
At a visit to the primary care clinic when the patient was 9 years old, his body-mass index had been in the overweight range. One year before the current presentation, he had had a Salter-Harris type 2 fracture of the left fifth finger.
The patient had been receiving omeprazole and had no known allergies to medications; immunizations were up to date. He lived with his parents and twin sister in a suburban area of New England. At school, he did well academically and participated in sports. He had recently been preparing intensively for a private-school entrance examination. His father had type 1 diabetes mellitus and hypertension, and a paternal uncle had hypothyroidism.
The results of the abdominal and general physical examinations were unchanged from those obtained at the primary care clinic, and an external rectal examination was normal. The dose of omeprazole was increased, and the patient was advised to keep a food and symptom diary and follow up with a psychologist. Laboratory test results are shown in Table 1. A diagnostic test was performed.
Eight days after presentation in the pediatric gastroenterology clinic of this hospital (13 days before this presentation), the patient's father called the clinic to report worsening of the patient's vomiting, weight loss, and fatigue; the patient also seemed to be breathing heavily at times and reported dizziness when walking. Ondansetron was prescribed by telephone and an esophagogastroduodenoscopy was scheduled for the next morning.
Dr. Maureen M. Leonard: The next day, the patient underwent esophagogastroduodenoscopy. The esophagus, stomach, and small intestine were visualized. The esophagus appeared normal. The gastric body also appeared normal; however, the gastric antrum was erythematous, which suggested the presence of inflammation. The second part of the duodenum had diffuse, moderate indentations of the circular folds (valves of Kerckring) that were described as moderately scalloped mucosa. Biopsy specimens of the distal esophagus, gastric antrum, and duodenum were obtained for histopathological examination. Other test results are shown in Table 1.
Dr. Lillemoe: Eleven days after the esophagogastroduodenoscopy, syncope occurred when the patient got up from bed in the early morning to use the bathroom. His parents called the gastroenterologist, who recommended evaluation in the emergency department at this hospital.
On arrival at the emergency department, the patient reported that the nausea and vomiting had not decreased, that his fatigue had progressively worsened, and that he felt weak. He had recently returned from a beach vacation in the southeastern United States, where he had used sunscreen and an umbrella for sun protection.
On examination, the patient was alert, interactive, and appeared thin. The temperature was 36.8[degrees]C, the pulse 87 beats per minute, the blood pressure 108/55 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The weight was 33.7 kg (20th percentile). The oral mucous membranes were dry. On examination of the abdomen, mild tenderness of the left upper quadrant was noted. The skin was markedly tan, most notably on light-exposed areas, including the face. The remainder of the physical examination was normal. An electrocardiogram showed normal sinus rhythm.
The patient was admitted to the hospital, additional diagnostic tests were performed, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 11-year-old boy was seen in the emergency department of this hospital because of ongoing vomiting and weight loss.
One month before this presentation, the patient was evaluated by his primary care pediatrician because of nausea, vomiting, decreased appetite, and weight loss. The patient and his parents reported that these symptoms had begun approximately 3 months earlier and had worsened during the past 3 weeks. The nausea and vomiting occurred in the early morning, abated later in the day, and were exacerbated by stress. The patient also reported fatigue and an intermittent sensation of regurgitation and burning in the throat. He had begun treatment with lansoprazole 5 days earlier, with no decrease in symptoms. On examination, the weight was 36.4 kg (37th percentile) and the height was 148.6 cm (58th percentile); at a visit to the primary care clinic 11 months earlier, the weight had been 40.5 kg (78th percentile) and the height had been 143.5 cm (62nd percentile). The abdomen was soft, with normal bowel sounds and without tenderness or masses. The remainder of the examination was normal. Laboratory test results are shown in Table 1. Omeprazole was prescribed, and the patient was referred to a pediatric gastroenterologist and a pediatric psychologist at this hospital.	
Table 1
On presentation to the pediatric gastroenterology clinic of this hospital (3 weeks before this presentation), the patient reported that the nausea and vomiting had decreased slightly after he had begun treatment with omeprazole, and then the symptoms had worsened. The vomitus was nonbloody and nonbilious. He had normal bowel movements, without blood, two or three times each day.
The patient was a twin and had been born by cesarean section at 36 weeks of gestation. During infancy, he had had gastroesophageal reflux disease (GERD) that was treated with ranitidine, omeprazole, and lansoprazole. He had been admitted to a local hospital because of bronchiolitis at 15 months of age, after which he had occasional episodes of wheezing.
When the patient was 5 years of age, decreased appetite, weight loss, and episodes of vomiting preceded by sore throat developed, and he was evaluated by a pediatric gastroenterologist at another hospital. At that time, an upper gastrointestinal series, performed after the administration of barium contrast, was normal. Tests for IgA and tissue transglutaminase IgA and IgG were negative. Lansoprazole and an antireflux diet were prescribed, and the symptoms resolved over a period of approximately 2 months, after which the proton-pump inhibitor was discontinued.
When the patient was 6 years of age, he was referred to a pediatric nephrologist at the other hospital because of hypertension. Renal ultrasonography was normal, and the results of ambulatory blood-pressure monitoring suggested the ""white coat"" effect (i.e., blood pressure elevated only in a clinical setting). The patient also had seasonal allergies, red-green color blindness, and a history of speech delay and retractile testes.
At a visit to the primary care clinic when the patient was 9 years old, his body-mass index had been in the overweight range. One year before the current presentation, he had had a Salter-Harris type 2 fracture of the left fifth finger.
The patient had been receiving omeprazole and had no known allergies to medications; immunizations were up to date. He lived with his parents and twin sister in a suburban area of New England. At school, he did well academically and participated in sports. He had recently been preparing intensively for a private-school entrance examination. His father had type 1 diabetes mellitus and hypertension, and a paternal uncle had hypothyroidism.
The results of the abdominal and general physical examinations were unchanged from those obtained at the primary care clinic, and an external rectal examination was normal. The dose of omeprazole was increased, and the patient was advised to keep a food and symptom diary and follow up with a psychologist. Laboratory test results are shown in Table 1. A diagnostic test was performed.
Eight days after presentation in the pediatric gastroenterology clinic of this hospital (13 days before this presentation), the patient's father called the clinic to report worsening of the patient's vomiting, weight loss, and fatigue; the patient also seemed to be breathing heavily at times and reported dizziness when walking. Ondansetron was prescribed by telephone and an esophagogastroduodenoscopy was scheduled for the next morning.
Dr. Maureen M. Leonard: The next day, the patient underwent esophagogastroduodenoscopy. The esophagus, stomach, and small intestine were visualized. The esophagus appeared normal. The gastric body also appeared normal; however, the gastric antrum was erythematous, which suggested the presence of inflammation. The second part of the duodenum had diffuse, moderate indentations of the circular folds (valves of Kerckring) that were described as moderately scalloped mucosa. Biopsy specimens of the distal esophagus, gastric antrum, and duodenum were obtained for histopathological examination. Other test results are shown in Table 1.
Dr. Lillemoe: Eleven days after the esophagogastroduodenoscopy, syncope occurred when the patient got up from bed in the early morning to use the bathroom. His parents called the gastroenterologist, who recommended evaluation in the emergency department at this hospital.
On arrival at the emergency department, the patient reported that the nausea and vomiting had not decreased, that his fatigue had progressively worsened, and that he felt weak. He had recently returned from a beach vacation in the southeastern United States, where he had used sunscreen and an umbrella for sun protection.
On examination, the patient was alert, interactive, and appeared thin. The temperature was 36.8[degrees]C, the pulse 87 beats per minute, the blood pressure 108/55 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The weight was 33.7 kg (20th percentile). The oral mucous membranes were dry. On examination of the abdomen, mild tenderness of the left upper quadrant was noted. The skin was markedly tan, most notably on light-exposed areas, including the face. The remainder of the physical examination was normal. An electrocardiogram showed normal sinus rhythm.
The patient was admitted to the hospital, additional diagnostic tests were performed, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of ongoing vomiting, weight loss, fatigue, and weakness, along with the physical examination findings of dry oral mucous membranes and tanned skin, suggest a possible endocrine disorder. The patient's history of GERD and the recent findings of erythematous gastric antrum and scalloped duodenal mucosa on esophagogastroduodenoscopy could suggest celiac disease, but the patient's symptoms did not improve with proton pump inhibitor treatment and the tests for IgA and tissue transglutaminase IgA and IgG were negative, making celiac disease less likely. The patient's tanned skin, particularly in light-exposed areas, is a classic sign of Addison's disease, a condition characterized by adrenal insufficiency. This condition can cause gastrointestinal symptoms such as nausea and vomiting, as well as fatigue, weakness, and weight loss due to inadequate production of cortisol. The patient's low blood pressure and syncope could be due to inadequate production of aldosterone, another hormone produced by the adrenal glands, which can lead to low blood volume and low blood pressure. Therefore, the most likely diagnosis is Addison's disease.""
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        ""content"": ""The patient's symptoms of ongoing vomiting, weight loss, fatigue, and weakness, along with physical findings of dry oral mucous membranes and tanned skin, suggest a possible endocrine disorder. The patient's history of gastroesophageal reflux disease (GERD) and the recent findings of an erythematous gastric antrum and scalloped duodenal mucosa on esophagogastroduodenoscopy could suggest a malabsorption syndrome, but these findings are not specific and could be secondary to the patient's primary condition. The patient's markedly tanned skin, most notable on light-exposed areas, is a key clue and is suggestive of increased production of melanocyte-stimulating hormone, which can occur in Addison's disease, a condition characterized by adrenal insufficiency. This condition can cause gastrointestinal symptoms such as nausea, vomiting, and weight loss, as well as fatigue and weakness due to inadequate production of cortisol. The patient's low blood pressure and syncope could be due to inadequate production of aldosterone, another hormone produced by the adrenal glands, leading to volume depletion. Therefore, the most likely diagnosis is Addison's disease.""
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        ""content"": ""The patient is an 11-year-old boy with a history of GERD, hypertension, and recent symptoms of nausea, vomiting, decreased appetite, and weight loss. The differential diagnosis for this patient includes gastrointestinal disorders such as GERD, peptic ulcer disease, and gastroparesis; metabolic disorders such as diabetes and hyperthyroidism; and psychological disorders such as anorexia nervosa and bulimia. The patient's history of GERD and the recent worsening of his symptoms suggest a gastrointestinal cause. However, the patient's hypertension and the recent onset of his symptoms suggest a possible metabolic disorder. The patient's recent stress related to his school entrance examination and his symptoms of nausea and vomiting also suggest a possible psychological disorder. However, the patient's physical examination findings of dry oral mucous membranes and tanned skin, along with his history of hypertension and his recent symptoms of nausea, vomiting, decreased appetite, and weight loss, suggest a possible diagnosis of Addison's disease. Addison's disease is a disorder of the adrenal glands that results in decreased production of cortisol and aldosterone, leading to symptoms such as fatigue, weight loss, nausea, vomiting, and hyperpigmentation of the skin. The patient's symptoms and physical examination findings are consistent with this diagnosis.\n\nDiagnosis: Addison's disease.""
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10.1056/NEJMcpc1904042,Case 40-2019: A 26-Year-Old Returning Traveler with Headache,"Hemoglobin (g/dl)   12.8
Hematocrit (%)   37.8
Platelet count (per μl)   339,000
White-cell count (per μl)   6160
Differential count (%)
Neutrophils   59.4
Lymphocytes   31.3
Monocytes   8.3
Eosinophils   0.5
Basophils   0.3
Immature granulocytes  0.2
C-reactive protein (mg/liter)  .0 0.4
Erythrocyte sedimentation rate (mm/hr)  0 5
Cerebrospinal fluid
Color Colorless Colorless
Turbidity Clear Moderate
Glucose (mg/dl)  28
Total protein (mg/dl)  680
Red-cell count (per μl)  4
Total nucleated cells (per μl)  1422
Differential count (%)
Segmented neutrophils 0 0
Lymphocytes  85
Reactive lymphocytes 0 4
Monocytes  11
Xanthochromia Not present Not present",Lymphocytic choriomeningitis virus infection.,Lymphocytic choriomeningitis virus infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 26-year-old woman with a history of migraines was evaluated in the emergency department of this hospital during the winter because of headache.
Three weeks before this presentation, the patient had traveled with her family to Europe for vacation. Nineteen days before this presentation, she visited a mountainous region, where she stayed in a mountain cabin and spent time outdoors in the snow. The cabin was located at an altitude above 3400 m. While in the mountains, she struck her head during a low-velocity sledding accident, after which she had a headache that lasted several hours and resolved spontaneously. She also had had mild chills and cough that she had attributed to spending time in cold weather.
Eight days before this presentation, a severe headache, which the patient described as the worst headache of her life, developed suddenly while she was eating dinner. The pain, located in the bitemporal regions and the occiput, was associated with fatigue, nausea, and vomiting. Unlike the patient's typical migraine headaches, the headache did not abate with either acetaminophen or naproxen therapy.
Five days before this presentation, neck stiffness and decreased range of motion in the neck developed. The patient was evaluated at a local emergency department, where she received a diagnosis of recurrent migraine; intravenous fluid and oral nonsteroidal antiinflammatory drugs were administered. She was able to continue traveling with her family, but severe headache persisted, which prompted her to return early to the United States.
One day before this presentation, the patient arrived at the Boston airport and was taken to the emergency department of another hospital. She reported ongoing severe headache and sensitivity to light and noise and a 1-week history of intermittent fever, chills, and night sweats, as well as constipation that had lasted several days. On examination, the temperature was 37[degrees]C, the pulse 90 beats per minute, the blood pressure 119/83 mm Hg, the respiratory rate 15 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. She was alert, awake, and appeared comfortable. The neck was supple, with full range of motion. No cervical lymphadenopathy or neurologic abnormalities were noted. After intravenous ketorolac, diphenhydramine, and metoclopramide were administered, there was a moderate decrease in the headache pain. Oral acetaminophen and ibuprofen were subsequently prescribed, and she was discharged home with instructions to contact her primary care physician if her symptoms did not resolve.
The next morning, the patient awoke with ongoing severe headache, nausea, and vomiting and presented to the emergency department of this hospital for evaluation. There was no weight loss, sore throat, shortness of breath, cough, chest pain, dysuria, rash, or mucocutaneous ulcers. Family members who had traveled with her had not had similar symptoms.
The patient had had varicella virus infection in childhood. She was originally from South America but had immigrated to the United States more than 15 years earlier. She was married, lived with her husband in a suburban region of New England, and worked in the health care industry. She was monogamous and reported no history of sexually transmitted illnesses. Vaccinations were up to date, and she had no known medication allergies. She had visited Canada and Mexico the year before presentation but reported no other travel in the preceding 3 years. She had a healthy dog. She had seen evidence of rodents around the mountain cabin where she stayed while traveling in Europe but otherwise had no known animal exposures or tick bites. She drank alcohol in moderation and did not smoke tobacco or use illicit drugs. Her mother and father were healthy, and no other family members were ill.
On examination, the patient was alert, was able to answer questions, and appeared comfortable. The temperature was 36.4[degrees]C, the pulse 91 beats per minute, the blood pressure 133/78 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. There was full range of motion in the neck, although flexion elicited mild pain in the posterior cervical region. No oropharyngeal ulcers or rashes were noted. The remainder of the examination was normal. Levels of electrolytes and results of renal-function tests were normal, as were blood levels of calcium, phosphorus, magnesium, and thyrotropin. Blood tests for antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative. Complement levels (C3 and C4) were normal. A urine test for beta human chorionic gonadotropin was negative. A test for heterophile antibodies was negative, as was a screening assay for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) antibodies and HIV-1 p24 antigen; HIV-1 RNA was not detected in the blood. Urinalysis revealed 1+ leukocyte esterase, 2+ blood, 1+ ketones, a pH of 7.0, and a specific gravity of 1.019; there were no red cells or white cells. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. McKinley Glover: Computed tomographic (CT) angiography of the head and neck revealed no intracranial hemorrhage, infarction, or mass lesion; arterial and venous vasculature appeared normal, with no stenosis. Multiple cervical lymph nodes were mildly enlarged but otherwise unremarkable in appearance, findings that were suggestive of reactive nodes (Figure 1).	
Figure 1 
Gadolinium-enhanced magnetic resonance imaging (MRI) of the head revealed no abnormal parenchymal, leptomeningeal, or pachymeningeal enhancement or infarction. Radiography of the chest was normal.
Dr. Altman: A lumbar puncture was performed. The cerebrospinal fluid (CSF) was cloudy and colorless; Gram's staining revealed abundant mononuclear cells and no organisms. There were 1422 total nucleated cells per microliter, of which 85% were lymphocytes. Nucleic acid testing for herpes simplex virus (HSV) DNA was negative; additional results of the CSF analysis are shown in Table 1. Blood cultures were obtained. Intravenous vancomycin, ceftriaxone, acyclovir, and ampicillin were administered, as were intravenous fluid, magnesium, diphenhydramine, magnesium, and metoclopramide.
The patient was admitted to this hospital, and additional test results were received. Nucleic acid testing for influenza A and B viruses and respiratory syncytial virus was negative, as were tests of a nasopharyngeal swab for human metapneumovirus, adenovirus, and parainfluenza virus antigens. Blood tests for antibodies to Borrelia burgdorferi and syphilis were nonreactive, and tests for 1,3-[beta]-d-glucan and serum cryptococcal antigen were negative. Severe headache continued, and intravenous ketorolac and hydromorphone were administered for pain. A diagnostic test result was received
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 26-year-old woman with a history of migraines was evaluated in the emergency department of this hospital during the winter because of headache.
Three weeks before this presentation, the patient had traveled with her family to Europe for vacation. Nineteen days before this presentation, she visited a mountainous region, where she stayed in a mountain cabin and spent time outdoors in the snow. The cabin was located at an altitude above 3400 m. While in the mountains, she struck her head during a low-velocity sledding accident, after which she had a headache that lasted several hours and resolved spontaneously. She also had had mild chills and cough that she had attributed to spending time in cold weather.
Eight days before this presentation, a severe headache, which the patient described as the worst headache of her life, developed suddenly while she was eating dinner. The pain, located in the bitemporal regions and the occiput, was associated with fatigue, nausea, and vomiting. Unlike the patient's typical migraine headaches, the headache did not abate with either acetaminophen or naproxen therapy.
Five days before this presentation, neck stiffness and decreased range of motion in the neck developed. The patient was evaluated at a local emergency department, where she received a diagnosis of recurrent migraine; intravenous fluid and oral nonsteroidal antiinflammatory drugs were administered. She was able to continue traveling with her family, but severe headache persisted, which prompted her to return early to the United States.
One day before this presentation, the patient arrived at the Boston airport and was taken to the emergency department of another hospital. She reported ongoing severe headache and sensitivity to light and noise and a 1-week history of intermittent fever, chills, and night sweats, as well as constipation that had lasted several days. On examination, the temperature was 37[degrees]C, the pulse 90 beats per minute, the blood pressure 119/83 mm Hg, the respiratory rate 15 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. She was alert, awake, and appeared comfortable. The neck was supple, with full range of motion. No cervical lymphadenopathy or neurologic abnormalities were noted. After intravenous ketorolac, diphenhydramine, and metoclopramide were administered, there was a moderate decrease in the headache pain. Oral acetaminophen and ibuprofen were subsequently prescribed, and she was discharged home with instructions to contact her primary care physician if her symptoms did not resolve.
The next morning, the patient awoke with ongoing severe headache, nausea, and vomiting and presented to the emergency department of this hospital for evaluation. There was no weight loss, sore throat, shortness of breath, cough, chest pain, dysuria, rash, or mucocutaneous ulcers. Family members who had traveled with her had not had similar symptoms.
The patient had had varicella virus infection in childhood. She was originally from South America but had immigrated to the United States more than 15 years earlier. She was married, lived with her husband in a suburban region of New England, and worked in the health care industry. She was monogamous and reported no history of sexually transmitted illnesses. Vaccinations were up to date, and she had no known medication allergies. She had visited Canada and Mexico the year before presentation but reported no other travel in the preceding 3 years. She had a healthy dog. She had seen evidence of rodents around the mountain cabin where she stayed while traveling in Europe but otherwise had no known animal exposures or tick bites. She drank alcohol in moderation and did not smoke tobacco or use illicit drugs. Her mother and father were healthy, and no other family members were ill.
On examination, the patient was alert, was able to answer questions, and appeared comfortable. The temperature was 36.4[degrees]C, the pulse 91 beats per minute, the blood pressure 133/78 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. There was full range of motion in the neck, although flexion elicited mild pain in the posterior cervical region. No oropharyngeal ulcers or rashes were noted. The remainder of the examination was normal. Levels of electrolytes and results of renal-function tests were normal, as were blood levels of calcium, phosphorus, magnesium, and thyrotropin. Blood tests for antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative. Complement levels (C3 and C4) were normal. A urine test for beta human chorionic gonadotropin was negative. A test for heterophile antibodies was negative, as was a screening assay for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) antibodies and HIV-1 p24 antigen; HIV-1 RNA was not detected in the blood. Urinalysis revealed 1+ leukocyte esterase, 2+ blood, 1+ ketones, a pH of 7.0, and a specific gravity of 1.019; there were no red cells or white cells. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. McKinley Glover: Computed tomographic (CT) angiography of the head and neck revealed no intracranial hemorrhage, infarction, or mass lesion; arterial and venous vasculature appeared normal, with no stenosis. Multiple cervical lymph nodes were mildly enlarged but otherwise unremarkable in appearance, findings that were suggestive of reactive nodes (Figure 1).	
Figure 1 
Gadolinium-enhanced magnetic resonance imaging (MRI) of the head revealed no abnormal parenchymal, leptomeningeal, or pachymeningeal enhancement or infarction. Radiography of the chest was normal.
Dr. Altman: A lumbar puncture was performed. The cerebrospinal fluid (CSF) was cloudy and colorless; Gram's staining revealed abundant mononuclear cells and no organisms. There were 1422 total nucleated cells per microliter, of which 85% were lymphocytes. Nucleic acid testing for herpes simplex virus (HSV) DNA was negative; additional results of the CSF analysis are shown in Table 1. Blood cultures were obtained. Intravenous vancomycin, ceftriaxone, acyclovir, and ampicillin were administered, as were intravenous fluid, magnesium, diphenhydramine, magnesium, and metoclopramide.
The patient was admitted to this hospital, and additional test results were received. Nucleic acid testing for influenza A and B viruses and respiratory syncytial virus was negative, as were tests of a nasopharyngeal swab for human metapneumovirus, adenovirus, and parainfluenza virus antigens. Blood tests for antibodies to Borrelia burgdorferi and syphilis were nonreactive, and tests for 1,3-[beta]-d-glucan and serum cryptococcal antigen were negative. Severe headache continued, and intravenous ketorolac and hydromorphone were administered for pain. A diagnostic test result was received
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 26-year-old woman presenting with severe headache, nausea, vomiting, neck stiffness, and decreased range of motion in the neck. She also has a history of migraines. The differential diagnosis for this patient includes meningitis, encephalitis, subarachnoid hemorrhage, and sinusitis. The patient's headache is described as the worst of her life and did not respond to typical migraine treatments, which makes a simple migraine less likely. The patient also has neck stiffness and decreased range of motion in the neck, which are symptoms often associated with meningitis. However, the patient's CT scan and MRI were normal, which makes subarachnoid hemorrhage and sinusitis less likely. The patient's CSF was cloudy and colorless with abundant mononuclear cells and no organisms, which is consistent with viral meningitis or encephalitis. However, the patient's nucleic acid testing for herpes simplex virus (HSV) DNA was negative, which makes HSV encephalitis less likely. The patient also has a history of recent travel to a mountainous region in Europe and exposure to rodents, which could suggest a zoonotic infection such as hantavirus or tick-borne encephalitis. However, the patient's blood tests for antibodies to Borrelia burgdorferi and syphilis were nonreactive, which makes these less likely. \n\nDiagnosis: Viral meningitis is the most likely diagnosis.""
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10.1056/NEJMcpc1904048,Case 37-2019: A 20-Month-Old Boy with Severe Anemia,"Hemoglobin (g/dl) 2.2
Hematocrit (%)  6.7
White-cell count (per μl)  36,450
Platelet count (per μl) 135,00 0,000 995,000
Red-cell count (per μl)  72,000
Mean corpuscular volume (fl) 7 6 93.1
Mean corpuscular hemoglobin (pg)  30.6
Mean corpuscular hemoglobin concentration (g/dl)  32.8
Red-cell distribution width (%) 17.2
Mean platelet volume (fl)  12.8
Reticulocyte count (%)  1.2
Prothrombin time (sec)   20.5
Prothrombin-time international normalized ratio   1.9
Activated partial-thromboplastin time (sec)  19.0
Sodium (mmol/liter)  140
Potassium (mmol/liter)  5.1
Chloride (mmol/liter)  102
Carbon dioxide (mmol/liter) 2 1 14
Anion gap (mmol/liter)   24
Calcium (mg/dl)  8.5
Phosphorus (mg/dl)  3.6
Magnesium (mg/dl)  3.4
Urea nitrogen (mg/dl) 9–23 29
Creatinine (mg/dl) 0.50–1.30 0.41
Glucose (mg/dl) 74–106 119
Alanine aminotransferase (U/liter) 10–49 17
Aspartate aminotransferase (U/liter) 6–40 28
Alkaline phosphatase (U/liter) 7 50 103
Bilirubin (mg/dl)
Total  0.7
Direct 0.2
Protein (mg/dl)
Total  6.5
Albumin 4.0
Globulin   2.5
Amylase (U/liter) 3 8 3
Lipase (U/liter) 5
Lactate dehydrogenase (U/liter) 16 70 808
Uric acid (mg/dl) 13.8
C-reactive protein (mg/liter)  7.3
Procalcitonin (ng/ml) 0.00–0.08 0.33",Juvenile myelomonocytic leukemia.,"Neurofibromatosis type 1 and severe anemia, probably due to leukemia.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 20-month-old boy was admitted to the pediatric intensive care unit of this hospital because of severe anemia.
The patient was well until 5 days before admission, when his aunt noted that he had begun tugging his ear and suspected that he might be having pain. He did not have fever, nasal congestion, rhinorrhea, or cough. His aunt took him to the emergency department at another hospital, where acute otitis media was diagnosed and a course of oral amoxicillin was prescribed.
The next day, the patient began vomiting. During the next 3 days, multiple episodes of nonbloody, nonbilious emesis occurred. His aunt fed him an oral electrolyte solution. During this time, the patient did not have a bowel movement. He also appeared pale, was less active than usual, and had a decreased volume of urine output. The day before admission, he drank milk and ate pizza without vomiting, but he seemed tired and increasingly pale. On the morning of admission, the patient's aunt took him to a primary care pediatric clinic for evaluation.
In the clinic, the patient appeared ill; pallor, tachycardia, and tachypnea were present. The hemoglobin level, obtained by fingerstick testing, was reportedly 2.9 g per deciliter, the hematocrit 9.0%, and the white-cell count 33,000 per microliter. The patient was referred to the emergency department of a community hospital affiliated with this hospital for further evaluation.
In the emergency department, the patient's aunt reported that the child seemed to be short of breath. On examination, he appeared listless and pale and had occasional grunting. The temperature was 36.8[degrees]C, the pulse 150 beats per minute, the blood pressure 84/59 mm Hg, the respiratory rate 44 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The weight was 11.7 kg (61st percentile for age). The mucous membranes were pale. On auscultation of the heart, tachycardia and a gallop rhythm were present. The radial and dorsalis pedis pulses were normal, and the capillary refill time was less than 2 seconds. The lungs were clear. The abdomen was distended, and hepatosplenomegaly was present, with no tenderness or masses and with normal bowel sounds. There was firm stool in the rectal vault; a fecal occult blood test was negative. Multiple cafe au lait macules were present. The remainder of the examination was normal. A peripheral intravenous catheter was inserted, and supplemental oxygen was administered through a nasal cannula at a rate of 3 liters per minute. A blood sample was obtained for culture and laboratory testing; the hematocrit was 6.7%, the white-cell count 36,450 per microliter, and the platelet count 995,000 per microliter. Other laboratory test results are shown in Table 1.	
Table 1
Dr. Randheer Shailam: Frontal and lateral chest radiographs showed hyperinflated lungs, cardiomegaly, and enlargement of the central pulmonary vessels (Figure 1A and 1B). There was no evidence of pleural effusion. These findings are nonspecific and can be present in patients with congenital heart diseases, including those with a left-to-right shunt, cardiomyopathy, or heart failure.	
Figure 1
Dr. Ana M. Rosales: An electrocardiogram (Figure 2A) showed sinus tachycardia at a rate of 155 beats per minute with left ventricular hypertrophy and nonspecific T-wave abnormalities. The QRS axis of depolarization was 54 degrees. The QRS duration and the remainder of the intervals were normal for the patient's age. The estimated corrected QT (QTc) interval was 404 msec.	
Figure 2 
Dr. de Paz: After consultation with a pediatric hematologist-oncologist was obtained, the patient was transferred to the pediatric intensive care unit at this hospital.
On admission of the patient to this hospital, the aunt reported that the child had not been seen by a pediatrician as frequently as is typically recommended for infants and toddlers because of a complex social situation; she did not think that he had ever undergone any blood testing. He had not received all the recommended routine immunizations; a detailed vaccination history was not immediately available. The patient had been born after 36 weeks 5 days of gestation and had been treated with oral morphine after birth because of neonatal abstinence syndrome. He was receiving amoxicillin and had no known allergies. He lived with his aunt and cousins in an urban area of New England and had not traveled. His diet included a variety of foods, including meats and vegetables, and he typically drank 0.6 liters of cow's milk each day. His father had multiple cafe au lait macules, and his mother and father had substance-use disorders.
On examination, the patient was whimpering and reaching out to be held by his aunt; he appeared ill and pale. The temperature was 36.2[degrees]C, the pulse 155 beats per minute, the blood pressure 98/49 mm Hg, the respiratory rate 66 breaths per minute, and the oxygen saturation 100% while he was breathing oxygen through a nasal cannula at a rate of 3 liters per minute. On auscultation of the heart, tachycardia, a gallop rhythm, and a systolic murmur (grade 4/6) were present; the precordium was hyperdynamic. Tachypnea, nasal flaring, abdominal breathing, and mild subcostal retractions were present, and soft crackles could be heard occasionally on examination of the lungs. The abdomen was distended, the spleen extended 6 cm below the left costal margin, and the liver extended 5 cm below the right costal margin. The hands and feet were cool, and the capillary refill time was less than 2 seconds. On examination of the skin, multiple cafe au lait macules were noted, as were inguinal freckling and a hemangioma on the right buttock that measured 1 cm in diameter. The remainder of the examination was normal.
Dr. Shailam: An anteroposterior radiograph of the chest showed severe cardiomegaly with mild interstitial pulmonary edema (Figure 1C).
Dr. Rosales: Echocardiography (Figure 2B through 2E) revealed normal segmental anatomy, with a patent foramen ovale and left-to-right blood flow. No septal defects were identified. The valvular anatomy was normal, and there was mild mitral regurgitation with mild enlargement of both atria. The origin and proximal course of the coronary arteries appeared normal. The pulmonary and systemic venous return appeared normal. The aortic arch had normal branching and was not obstructed. There was no evidence of a ductus arteriosus. The left ventricle was moderately to severely dilated, with preserved systolic function.
Dr. de Paz: A diagnostic test result was received, and additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 20-month-old boy was admitted to the pediatric intensive care unit of this hospital because of severe anemia.
The patient was well until 5 days before admission, when his aunt noted that he had begun tugging his ear and suspected that he might be having pain. He did not have fever, nasal congestion, rhinorrhea, or cough. His aunt took him to the emergency department at another hospital, where acute otitis media was diagnosed and a course of oral amoxicillin was prescribed.
The next day, the patient began vomiting. During the next 3 days, multiple episodes of nonbloody, nonbilious emesis occurred. His aunt fed him an oral electrolyte solution. During this time, the patient did not have a bowel movement. He also appeared pale, was less active than usual, and had a decreased volume of urine output. The day before admission, he drank milk and ate pizza without vomiting, but he seemed tired and increasingly pale. On the morning of admission, the patient's aunt took him to a primary care pediatric clinic for evaluation.
In the clinic, the patient appeared ill; pallor, tachycardia, and tachypnea were present. The hemoglobin level, obtained by fingerstick testing, was reportedly 2.9 g per deciliter, the hematocrit 9.0%, and the white-cell count 33,000 per microliter. The patient was referred to the emergency department of a community hospital affiliated with this hospital for further evaluation.
In the emergency department, the patient's aunt reported that the child seemed to be short of breath. On examination, he appeared listless and pale and had occasional grunting. The temperature was 36.8[degrees]C, the pulse 150 beats per minute, the blood pressure 84/59 mm Hg, the respiratory rate 44 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The weight was 11.7 kg (61st percentile for age). The mucous membranes were pale. On auscultation of the heart, tachycardia and a gallop rhythm were present. The radial and dorsalis pedis pulses were normal, and the capillary refill time was less than 2 seconds. The lungs were clear. The abdomen was distended, and hepatosplenomegaly was present, with no tenderness or masses and with normal bowel sounds. There was firm stool in the rectal vault; a fecal occult blood test was negative. Multiple cafe au lait macules were present. The remainder of the examination was normal. A peripheral intravenous catheter was inserted, and supplemental oxygen was administered through a nasal cannula at a rate of 3 liters per minute. A blood sample was obtained for culture and laboratory testing; the hematocrit was 6.7%, the white-cell count 36,450 per microliter, and the platelet count 995,000 per microliter. Other laboratory test results are shown in Table 1.	
Table 1
Dr. Randheer Shailam: Frontal and lateral chest radiographs showed hyperinflated lungs, cardiomegaly, and enlargement of the central pulmonary vessels (Figure 1A and 1B). There was no evidence of pleural effusion. These findings are nonspecific and can be present in patients with congenital heart diseases, including those with a left-to-right shunt, cardiomyopathy, or heart failure.	
Figure 1
Dr. Ana M. Rosales: An electrocardiogram (Figure 2A) showed sinus tachycardia at a rate of 155 beats per minute with left ventricular hypertrophy and nonspecific T-wave abnormalities. The QRS axis of depolarization was 54 degrees. The QRS duration and the remainder of the intervals were normal for the patient's age. The estimated corrected QT (QTc) interval was 404 msec.	
Figure 2 
Dr. de Paz: After consultation with a pediatric hematologist-oncologist was obtained, the patient was transferred to the pediatric intensive care unit at this hospital.
On admission of the patient to this hospital, the aunt reported that the child had not been seen by a pediatrician as frequently as is typically recommended for infants and toddlers because of a complex social situation; she did not think that he had ever undergone any blood testing. He had not received all the recommended routine immunizations; a detailed vaccination history was not immediately available. The patient had been born after 36 weeks 5 days of gestation and had been treated with oral morphine after birth because of neonatal abstinence syndrome. He was receiving amoxicillin and had no known allergies. He lived with his aunt and cousins in an urban area of New England and had not traveled. His diet included a variety of foods, including meats and vegetables, and he typically drank 0.6 liters of cow's milk each day. His father had multiple cafe au lait macules, and his mother and father had substance-use disorders.
On examination, the patient was whimpering and reaching out to be held by his aunt; he appeared ill and pale. The temperature was 36.2[degrees]C, the pulse 155 beats per minute, the blood pressure 98/49 mm Hg, the respiratory rate 66 breaths per minute, and the oxygen saturation 100% while he was breathing oxygen through a nasal cannula at a rate of 3 liters per minute. On auscultation of the heart, tachycardia, a gallop rhythm, and a systolic murmur (grade 4/6) were present; the precordium was hyperdynamic. Tachypnea, nasal flaring, abdominal breathing, and mild subcostal retractions were present, and soft crackles could be heard occasionally on examination of the lungs. The abdomen was distended, the spleen extended 6 cm below the left costal margin, and the liver extended 5 cm below the right costal margin. The hands and feet were cool, and the capillary refill time was less than 2 seconds. On examination of the skin, multiple cafe au lait macules were noted, as were inguinal freckling and a hemangioma on the right buttock that measured 1 cm in diameter. The remainder of the examination was normal.
Dr. Shailam: An anteroposterior radiograph of the chest showed severe cardiomegaly with mild interstitial pulmonary edema (Figure 1C).
Dr. Rosales: Echocardiography (Figure 2B through 2E) revealed normal segmental anatomy, with a patent foramen ovale and left-to-right blood flow. No septal defects were identified. The valvular anatomy was normal, and there was mild mitral regurgitation with mild enlargement of both atria. The origin and proximal course of the coronary arteries appeared normal. The pulmonary and systemic venous return appeared normal. The aortic arch had normal branching and was not obstructed. There was no evidence of a ductus arteriosus. The left ventricle was moderately to severely dilated, with preserved systolic function.
Dr. de Paz: A diagnostic test result was received, and additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with severe anemia, vomiting, pallor, decreased activity, decreased urine output, and hepatosplenomegaly. The presence of multiple cafe au lait macules and inguinal freckling suggests a diagnosis of neurofibromatosis type 1 (NF1). NF1 is associated with various complications, including juvenile myelomonocytic leukemia (JMML), which can present with symptoms of anemia, hepatosplenomegaly, and pallor. The patient's high white blood cell count is also suggestive of leukemia. Therefore, the most likely diagnosis is juvenile myelomonocytic leukemia in a patient with neurofibromatosis type 1.""
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        ""content"": ""The patient is a 20-month-old boy presenting with severe anemia, vomiting, pallor, decreased activity, decreased urine output, tachycardia, tachypnea, hepatosplenomegaly, and multiple cafe au lait macules. The differential diagnosis includes various causes of anemia such as iron deficiency anemia, hemolytic anemia, aplastic anemia, and anemia due to chronic disease. The presence of hepatosplenomegaly and multiple cafe au lait macules, however, narrows the differential to conditions that present with these findings, such as neurofibromatosis, tuberous sclerosis, and Fanconi anemia. Neurofibromatosis and tuberous sclerosis are primarily neurological disorders and do not typically present with severe anemia, making them less likely. Fanconi anemia, on the other hand, is a genetic disorder that leads to bone marrow failure and can present with the findings seen in this patient. The presence of multiple cafe au lait macules, a common finding in Fanconi anemia, further supports this diagnosis. \n\nDiagnosis: Fanconi anemia.""
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10.1056/NEJMcpc1909625,"Case 36-2019: A 34-Year-Old Man with Dyspnea, Odynophagia, and Abdominal Pain","Hemoglobin (g/dl)  11.6   9.1
Hematocrit (%) 35.5   28.0
White-cell count (per μl)   8590   6200
Differential count (%)
Neutrophils  77.1   79.4
Immature granulocytes  0.6
Lymphocytes 18.0   13.2
Monocytes  3.4   6.0
Eosinophils 1.4   0.6
Basophils 0.1   0.2
Red-cell count (per μl)  4,360,000   3,390,000
Platelet count (per μl)   506,000   389,000
Prothrombin time (sec)   15.6
Prothrombin-time international 
normalized ratio
  1.3
Activated partial-thromboplastin 
time (sec)
22. 6.0 26.5
Fibrinogen (mg/dl)  581
Sodium (mmol/liter)  136
Potassium (mmol/liter)   4.2
Chloride (mmol/liter)  97
Carbon dioxide (mmol/liter)  21
Anion gap (mmol/liter)  18
Alanine aminotransferase (U/liter) 55
Aspartate aminotransferase (U/liter) 77
Protein (g/dl)
Total  8.3
Albumin 3.5–5.2 3.2
Globulin  5.1
Lactate dehydrogenase (U/liter) 11 10 646
Arterial blood gases
Fraction of inspired oxygen Unspecified
pH   7.39
Partial pressure of carbon dioxide 
(mm Hg)
  27
Partial pressure of oxygen 
(mm Hg)
  106
",Kaposi‚Äö√Ñ√¥s sarcoma of the gastrointestinal tract,Kaposi’s sarcoma of the gastrointestinal tract.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 34-year-old man with asthma was admitted to this hospital during the winter because of dyspnea.
Three months before admission, odynophagia developed, and the patient noted white plaques in his mouth. He presented to an urgent care clinic, where a clinical diagnosis of thrush was made, and an oral suspension of nystatin was prescribed.
One month before admission, exertional dyspnea and a cough developed. The cough was intermittently productive of thick, grayish sputum that occasionally contained a small amount of blood. The patient used an albuterol metered-dose inhaler, but the dyspnea progressively worsened. Two weeks before admission, fatigue, myalgias, night sweats, shaking chills, and midsternal chest pain developed. During the 3 days before admission, the patient also noted fevers. On the morning of admission, because of the progressive dyspnea and odynophagia, the patient presented to the emergency department at another hospital for evaluation.
On examination at the other hospital, the patient was cachectic and appeared ill. The temperature was 38.7[degrees]C, the pulse 121 beats per minute, the blood pressure 96/65 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 95% while he was breathing ambient air. The height was 170 cm, the weight 49.9 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 17.3. The mucous membranes were dry, and white plaques were noted throughout the mouth and posterior oropharynx. The lungs were clear, with no crackles, rhonchi, or wheezes. The red-cell indexes and blood levels of glucose, calcium, alkaline phosphatase, total bilirubin, direct bilirubin, and lactic acid were normal, as were the results of renal-function tests and urinalysis; other laboratory test results are shown in Table 1. Culture of a nasopharyngeal swab for influenza type A and B antigens was negative, and a rapid screening test for human immunodeficiency virus (HIV) antibodies was positive. An electrocardiogram showed sinus tachycardia. Intravenous fluids, acetaminophen, and ketorolac were administered, and imaging studies of the chest were performed.	
Table 1
Dr. Dexter P. Mendoza: A posteroanterior chest radiograph (Figure 1A) showed diffuse, hazy airspace opacities that were more prominent on the right side than on the left side, with slight perihilar predominance. Subsequent computed tomography (CT) of the chest, performed after the administration of intravenous contrast material (Figure 1B), revealed diffuse ground-glass opacities bilaterally; there was no evidence of mediastinal or hilar lymphadenopathy or pleural effusion.	
Figure 1 
Dr. Ankomah: Two hours after the patient arrived at the emergency department of the other hospital, the oxygen saturation decreased to 91% and the blood pressure decreased to 81/42 mm Hg. Supplemental oxygen was administered through a nasal cannula at a rate of 2 liters per minute, a central venous catheter was placed in the right internal jugular vein, and a continuous infusion of norepinephrine at a rate of 4 [mu]g per minute was initiated. The blood pressure increased to 106/64 mm Hg. Trimethoprim-sulfamethoxazole, ceftriaxone, and levofloxacin were administered intravenously, and the patient was transferred to the emergency department of this hospital.
On arrival at this hospital, the patient's blood pressure was normal, and the norepinephrine infusion was stopped; additional history was obtained. The patient reported a diffuse headache. During the preceding 2 months, he had lost approximately 13.6 kg of weight and had had nausea, intermittent vomiting, and mild, diffuse abdominal pain. He had a history of depression, anxiety, and asthma. Thirteen years earlier, he had been treated for gonorrhea and chlamydia. Medications included inhaled albuterol, inhaled budesonide-formoterol, and oral alprazolam as needed. He had no known allergies.
The patient was of Mediterranean descent, had been born in the southwestern United States, and had traveled to northern Africa in the remote past. He had unstable housing and slept in shelters or at the homes of friends and family in coastal New England, where he worked on a seasonal basis. He had smoked approximately 10 cigarettes per day since he was 18 years of age, drank two glasses of wine every evening, and smoked marijuana occasionally; he did not inject illicit drugs. He had had 20 previous sexual partners, both men and women, and had used condoms inconsistently.
On examination, the patient appeared chronically ill. The temperature was 36.8[degrees]C, the pulse 102 beats per minute, the blood pressure 110/56 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while he was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. Auscultation of the lungs revealed scattered bibasilar crackles. Examination of the skin revealed diffuse xerosis, scattered hypopigmented macules on the arms, and a violaceous plaque with irregular borders on the plantar aspect of the medial right foot. The remainder of the examination was unchanged. Tests for pneumococcal and legionella antigens in the urine were negative, and the blood level of 1,3-[beta]-d-glucan was greater than 500 pg per milliliter (normal value, <60). A clinical diagnosis of Pneumocystis jirovecii pneumonia was made. Treatment with trimethoprim-sulfamethoxazole was continued, treatment with ceftriaxone and levofloxacin was discontinued, and treatment with vancomycin, cefepime, fluconazole, and prednisone was initiated. The patient was admitted to this hospital.
On the second hospital day, additional laboratory test results were received. A screening assay for HIV type 1 (HIV-1) and HIV type 2 (HIV-2) antibodies and HIV-1 p24 antigen was positive, and an antibody differentiation assay confirmed the diagnosis of HIV-1 infection. The plasma HIV-1 RNA viral load was 363,000 copies per milliliter, and the blood CD4+ T-cell count was 77 per cubic millimeter (reference range, 348 to 1456); 11% of the lymphocytes were CD4+ T cells (reference range, 21 to 64). A blood test for Treponema pallidum antibodies was positive, a rapid plasma reagin test was negative, and a T. pallidum particle agglutination assay was positive. A lumbar puncture revealed clear cerebrospinal fluid with no red or white cells and normal levels of protein and glucose; a Venereal Disease Research Laboratory test was negative. Three induced sputum smears that were examined for acid-fast bacilli were negative, as were a sputum polymerase-chain-reaction (PCR) test for Mycobacterium tuberculosis, an interferon-[gamma] release assay for cell-mediated immune response to M. tuberculosis, and a blood test for cryptococcal antigen. A test for cytomegalovirus IgG antibodies was positive, and the result of a PCR test for cytomegalovirus DNA performed on a blood specimen was undetectable.
The patient's dyspnea and cough gradually abated, and treatment with supplemental oxygen, vancomycin, and cefepime was discontinued. On the fourth hospital day, a 2-week course of intravenous penicillin was initiated.
On the fifth hospital day, the patient reported that his abdominal pain had increased. The pain was diffuse, moderate in intensity, and sharp, and it worsened when he was in the supine position. On examination, the abdomen was soft, with diffuse tenderness on palpation that was most severe in the right and left upper quadrants.
Dr. Mendoza: CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a moderate fecal load but was otherwise normal.
Dr. Ankomah: Polyethylene glycol and senna were administered. On the sixth hospital day, a fixed-dose formulation of bictegravir, emtricitabine, and tenofovir alafenamide was started, and the dosage of prednisone was decreased.
During the next 4 days, the abdominal pain worsened and was associated with abdominal distention, nausea, several episodes of blood-tinged emesis, and loose stools. On examination, the abdomen was diffusely tender on palpation; normal bowel sounds were present. Laboratory studies revealed stable liver-function test results and a blood lactic acid level of 4.1 mmol per liter (reference range, 0.5 to 2.0).
Dr. Mendoza: Repeat CT angiography of the abdomen and pelvis was normal.
Dr. Ankomah: Intravenous fluids were administered, and the blood lactic acid level normalized.
A diagnostic procedure was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 34-year-old man with asthma was admitted to this hospital during the winter because of dyspnea.
Three months before admission, odynophagia developed, and the patient noted white plaques in his mouth. He presented to an urgent care clinic, where a clinical diagnosis of thrush was made, and an oral suspension of nystatin was prescribed.
One month before admission, exertional dyspnea and a cough developed. The cough was intermittently productive of thick, grayish sputum that occasionally contained a small amount of blood. The patient used an albuterol metered-dose inhaler, but the dyspnea progressively worsened. Two weeks before admission, fatigue, myalgias, night sweats, shaking chills, and midsternal chest pain developed. During the 3 days before admission, the patient also noted fevers. On the morning of admission, because of the progressive dyspnea and odynophagia, the patient presented to the emergency department at another hospital for evaluation.
On examination at the other hospital, the patient was cachectic and appeared ill. The temperature was 38.7[degrees]C, the pulse 121 beats per minute, the blood pressure 96/65 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 95% while he was breathing ambient air. The height was 170 cm, the weight 49.9 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 17.3. The mucous membranes were dry, and white plaques were noted throughout the mouth and posterior oropharynx. The lungs were clear, with no crackles, rhonchi, or wheezes. The red-cell indexes and blood levels of glucose, calcium, alkaline phosphatase, total bilirubin, direct bilirubin, and lactic acid were normal, as were the results of renal-function tests and urinalysis; other laboratory test results are shown in Table 1. Culture of a nasopharyngeal swab for influenza type A and B antigens was negative, and a rapid screening test for human immunodeficiency virus (HIV) antibodies was positive. An electrocardiogram showed sinus tachycardia. Intravenous fluids, acetaminophen, and ketorolac were administered, and imaging studies of the chest were performed.	
Table 1
Dr. Dexter P. Mendoza: A posteroanterior chest radiograph (Figure 1A) showed diffuse, hazy airspace opacities that were more prominent on the right side than on the left side, with slight perihilar predominance. Subsequent computed tomography (CT) of the chest, performed after the administration of intravenous contrast material (Figure 1B), revealed diffuse ground-glass opacities bilaterally; there was no evidence of mediastinal or hilar lymphadenopathy or pleural effusion.	
Figure 1 
Dr. Ankomah: Two hours after the patient arrived at the emergency department of the other hospital, the oxygen saturation decreased to 91% and the blood pressure decreased to 81/42 mm Hg. Supplemental oxygen was administered through a nasal cannula at a rate of 2 liters per minute, a central venous catheter was placed in the right internal jugular vein, and a continuous infusion of norepinephrine at a rate of 4 [mu]g per minute was initiated. The blood pressure increased to 106/64 mm Hg. Trimethoprim-sulfamethoxazole, ceftriaxone, and levofloxacin were administered intravenously, and the patient was transferred to the emergency department of this hospital.
On arrival at this hospital, the patient's blood pressure was normal, and the norepinephrine infusion was stopped; additional history was obtained. The patient reported a diffuse headache. During the preceding 2 months, he had lost approximately 13.6 kg of weight and had had nausea, intermittent vomiting, and mild, diffuse abdominal pain. He had a history of depression, anxiety, and asthma. Thirteen years earlier, he had been treated for gonorrhea and chlamydia. Medications included inhaled albuterol, inhaled budesonide-formoterol, and oral alprazolam as needed. He had no known allergies.
The patient was of Mediterranean descent, had been born in the southwestern United States, and had traveled to northern Africa in the remote past. He had unstable housing and slept in shelters or at the homes of friends and family in coastal New England, where he worked on a seasonal basis. He had smoked approximately 10 cigarettes per day since he was 18 years of age, drank two glasses of wine every evening, and smoked marijuana occasionally; he did not inject illicit drugs. He had had 20 previous sexual partners, both men and women, and had used condoms inconsistently.
On examination, the patient appeared chronically ill. The temperature was 36.8[degrees]C, the pulse 102 beats per minute, the blood pressure 110/56 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while he was receiving supplemental oxygen through a nasal cannula at a rate of 2 liters per minute. Auscultation of the lungs revealed scattered bibasilar crackles. Examination of the skin revealed diffuse xerosis, scattered hypopigmented macules on the arms, and a violaceous plaque with irregular borders on the plantar aspect of the medial right foot. The remainder of the examination was unchanged. Tests for pneumococcal and legionella antigens in the urine were negative, and the blood level of 1,3-[beta]-d-glucan was greater than 500 pg per milliliter (normal value, <60). A clinical diagnosis of Pneumocystis jirovecii pneumonia was made. Treatment with trimethoprim-sulfamethoxazole was continued, treatment with ceftriaxone and levofloxacin was discontinued, and treatment with vancomycin, cefepime, fluconazole, and prednisone was initiated. The patient was admitted to this hospital.
On the second hospital day, additional laboratory test results were received. A screening assay for HIV type 1 (HIV-1) and HIV type 2 (HIV-2) antibodies and HIV-1 p24 antigen was positive, and an antibody differentiation assay confirmed the diagnosis of HIV-1 infection. The plasma HIV-1 RNA viral load was 363,000 copies per milliliter, and the blood CD4+ T-cell count was 77 per cubic millimeter (reference range, 348 to 1456); 11% of the lymphocytes were CD4+ T cells (reference range, 21 to 64). A blood test for Treponema pallidum antibodies was positive, a rapid plasma reagin test was negative, and a T. pallidum particle agglutination assay was positive. A lumbar puncture revealed clear cerebrospinal fluid with no red or white cells and normal levels of protein and glucose; a Venereal Disease Research Laboratory test was negative. Three induced sputum smears that were examined for acid-fast bacilli were negative, as were a sputum polymerase-chain-reaction (PCR) test for Mycobacterium tuberculosis, an interferon-[gamma] release assay for cell-mediated immune response to M. tuberculosis, and a blood test for cryptococcal antigen. A test for cytomegalovirus IgG antibodies was positive, and the result of a PCR test for cytomegalovirus DNA performed on a blood specimen was undetectable.
The patient's dyspnea and cough gradually abated, and treatment with supplemental oxygen, vancomycin, and cefepime was discontinued. On the fourth hospital day, a 2-week course of intravenous penicillin was initiated.
On the fifth hospital day, the patient reported that his abdominal pain had increased. The pain was diffuse, moderate in intensity, and sharp, and it worsened when he was in the supine position. On examination, the abdomen was soft, with diffuse tenderness on palpation that was most severe in the right and left upper quadrants.
Dr. Mendoza: CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a moderate fecal load but was otherwise normal.
Dr. Ankomah: Polyethylene glycol and senna were administered. On the sixth hospital day, a fixed-dose formulation of bictegravir, emtricitabine, and tenofovir alafenamide was started, and the dosage of prednisone was decreased.
During the next 4 days, the abdominal pain worsened and was associated with abdominal distention, nausea, several episodes of blood-tinged emesis, and loose stools. On examination, the abdomen was diffusely tender on palpation; normal bowel sounds were present. Laboratory studies revealed stable liver-function test results and a blood lactic acid level of 4.1 mmol per liter (reference range, 0.5 to 2.0).
Dr. Mendoza: Repeat CT angiography of the abdomen and pelvis was normal.
Dr. Ankomah: Intravenous fluids were administered, and the blood lactic acid level normalized.
A diagnostic procedure was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of dyspnea, cough, and fever, along with the presence of diffuse ground-glass opacities on chest imaging, are suggestive of a pulmonary infection. The patient's history of thrush, weight loss, and positive HIV test indicate an immunocompromised state, which makes him susceptible to opportunistic infections. The elevated level of 1,3-beta-D-glucan in the blood is a marker for fungal infections, particularly Pneumocystis jirovecii pneumonia, which is common in patients with HIV/AIDS. The patient's symptoms improved with treatment for Pneumocystis jirovecii pneumonia, further supporting this diagnosis.\n\nDiagnosis: Pneumocystis jirovecii pneumonia in a patient with HIV/AIDS.""
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}",Pneumocystis jirovecii pneumonia in a patient with HIV/AIDS,N,"{
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        ""content"": ""The patient is a 34-year-old man with a history of asthma, presenting with dyspnea, odynophagia, and white plaques in his mouth. He also has a history of weight loss, nausea, vomiting, and abdominal pain. He has a positive HIV test and a diagnosis of Pneumocystis jirovecii pneumonia. The differential diagnosis for this patient includes HIV-related conditions such as oral candidiasis (thrush), Pneumocystis jirovecii pneumonia, and other opportunistic infections. The presence of white plaques in his mouth and a previous diagnosis of thrush suggest oral candidiasis. His dyspnea, cough, and the presence of diffuse ground-glass opacities on chest CT are consistent with Pneumocystis jirovecii pneumonia, a common opportunistic infection in people with HIV. His abdominal pain, nausea, vomiting, and weight loss could be due to another opportunistic infection or a gastrointestinal manifestation of HIV. However, given his positive HIV test, the presence of oral candidiasis, and the diagnosis of Pneumocystis jirovecii pneumonia, it is likely that his symptoms are related to advanced HIV disease, also known as AIDS.\n\nDiagnosis: Advanced HIV disease/Acquired Immunodeficiency Syndrome (AIDS)""
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}",Advanced HIV disease/Acquired Immunodeficiency Syndrome (AIDS),N
10.1056/NEJMcpc1909627,Case 35-2019: A 66-Year-Old Man with Pancytopenia and Rash,"Hemoglobin (g/dl) 9.2   9.8
Hematocrit (%)  26.1   28.2
Mean corpuscular volume (fl)  89.4   89.5
Platelet count (per μl)  58,000   51,000
White-cell count (per μl) 800   940
Differential count (%)
Neutrophils  56   65.5
Lymphocytes 28   22.0
Monocytes   14   9.9
Reactive lymphocytes <1 2  
Immature granulocytes 0 1.3
Erythrocyte morphologic features Presence of microcytes, 
macrocytes, ovalocytes, 
polychromasia, schistocytes, acanthocytes, 
and teardrop cells
Presence of burr cells 
and schistocytes
International normalized ratio  1.7   1.3
Partial-thromboplastin time (sec) 24–36 70
Fibrinogen (mg/dl) 160–450 42 15 0 148
Thrombin time (sec) 11–15 38.8
d-Dimer (ng/ml) <230 712   4165
Lactate dehydrogenase (U/liter)   1,106 11 10 1301
Ferritin (ng/ml)  13,026 2 00 29,600
Triglycerides (mg/dl) <150, fasting 378   685
Haptoglobin (mg/dl) 25–200 <20 3 00  
Sodium (mmol/liter)   127   127
Albumin (g/dl) 3.2–5.2 2.0   1.8
Globulin (g/dl) 2.6   3.2
Total bilirubin (mg/dl)  2.9
Alkaline phosphatase (U/liter) 39–117 500   604
Aspartate aminotransferase (U/li‚Äë
ter)
 7 316   399
Alanine aminotransferase (U/liter)   141   119
≈í‚â•-Glutamyl transferase (U/liter)  615",Skin involvement associated with peripheral T-cell lymphoma most consistent with primary cutaneous gamma‚Äö√Ñ√¨delta T-cell lymphoma,Primary cutaneous gamma–delta T-cell lymphoma that triggered hemophagocytic lymphohistiocytosis syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 66-year-old man with a history of pancytopenia was transferred to this hospital in the winter for evaluation of pancytopenia and rash.
The patient had been well until 1 year before admission, when episodic fevers began to occur. Approximately 3 months before admission, fevers with a temperature of up to 38.3[degrees]C increased in frequency and severity and coincided with shaking chills. Scattered papules developed on the arms and legs; the lesions were initially deeply erythematous, but over a period of several days, the discoloration faded and the skin sloughed. There was no associated pruritus, and febrile episodes did not coincide with worsening of the skin lesions.
Two months before admission, episodes of orthostatic hypotension and dizziness developed. The patient was admitted to other hospitals on two occasions for recurrent lightheadedness. Laboratory evaluation reportedly revealed a normal level of corticotropin in the blood and a normal increase in the serum cortisol level after intravenous administration of cosyntropin. The white-cell count was 850 per microliter (reference range, 4200 to 9900), the hemoglobin level 9.2 g per deciliter (reference range, 13.0 to 17.4), the platelet count 61,000 per microliter (reference range, 140,000 to 440,000), and the mean corpuscular volume 89 fl (reference range, 82 to 100). The blood levels of aspartate aminotransferase and alanine aminotransferase were elevated. Serologic tests for hepatitis A, B, and C viruses and for human immunodeficiency virus (HIV) type 1 and type 2 were negative. The ferritin level was 12,620 ng per milliliter (reference range, 30 to 400), but subsequent testing for the HFE mutation most often associated with hemochromatosis was negative. Nineteen days before the ferritin level was measured, the iron level was 67 [mu]g per deciliter (12 [mu]mol per liter) (reference range, 45 to 182 [mu]g per deciliter [8 to 33 [mu]mol per liter]), the total iron-binding capacity 143 [mu]g per deciliter (26 [mu]mol per liter) (reference range, 261 to 478 [mu]g per deciliter [47 to 86 [mu]mol per liter]), the transferrin saturation 47% (reference range, 20 to 55), the folate level 18.3 ng per milliliter (41 nmol per liter) (reference range, 6 to 20 ng per milliliter [14 to 45 nmol per liter]), and the vitamin B12 level 861 pg per milliliter (635 pmol per liter) (reference range, 193 to 986 pg per milliliter [142 to 727 pmol per liter]). Magnetic resonance cholangiopancreatography revealed a small amount of pericholecystic fluid and mild edema in the right paracolic gutter that suggested an infiltrative process; the biliary ducts appeared normal, and no intrahepatic iron deposition was seen. The orthostatic hypotension abated, but did not fully resolve, after the administration of intravenous fluids. The patient was discharged home and was instructed to follow up with his primary care physician.
Eight days before admission, orthostatic hypotension recurred. The patient was readmitted to one of the other hospitals, where he reported ongoing lightheadedness and generalized weakness. The temperature was 36.6[degrees]C, the pulse 91 beats per minute, the blood pressure 119/71 mm Hg while the patient was in the supine position (75/48 while he was standing), the respiratory rate 16 breaths per minute, the oxygen saturation 95% while he was breathing ambient air, and the weight 74.9 kg. He was pale, appeared ill, and had marked edema of the legs and periorbital region. Scattered nummular and erosive lesions with overlying eschar were noted on both feet, both forearms, and the medial right thigh; petechiae were also seen on the arms and chest. The remainder of the examination was normal. Laboratory test results are shown in Table 1. An antibody-based screening test for Lyme disease was negative, as were nucleic acid tests for babesia, ehrlichia, anaplasma, adenovirus, and cytomegalovirus. Histoplasma and aspergillus antigens were not detected in the blood. Cultures of the blood were negative.	
Table 1 
A transthoracic echocardiogram was of technically poor quality but showed normal biventricular function; valvular dysfunction was not assessed. Radiography of the chest revealed atelectasis but was otherwise normal. Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, revealed small bilateral pleural effusions and no evidence of lymphadenopathy; CT of the abdomen and pelvis revealed normal hepatic parenchyma, a moderate amount of ascites, mild splenomegaly, and no evidence of lymphadenopathy. Positron-emission tomography (PET) from the skull base to the thighs, performed after the administration of intravenous 18F-fluorodeoxyglucose (FDG) tracer, revealed homogeneous FDG uptake in the spleen, and there was no evidence of hypermetabolism in the abdominal or pelvic lymph nodes.
The patient was transferred to this hospital for further evaluation and management of possible hemophagocytic lymphohistiocytosis (HLH).
Dr. Valentina Nardi: Examination of a bone marrow biopsy specimen and aspirate that were obtained at the other hospital revealed maturing trilineage hematopoiesis and mildly hypercellular marrow with many histiocytes and numerous engulfed erythroid elements in the cytoplasm. The findings were consistent with hemophagocytosis, with no evidence of infection or lymphoma (Figure 1).	
Figure 1
Dr. Kristine M. Cornejo: A punch biopsy of an erythematous lesion on the right thigh was performed at the other hospital. Microscopic examination of the specimen revealed focal epidermal erosion with impetiginized scale crust and a mild lymphohistiocytic infiltrate in the dermis and subcutaneous tissue; no fungal organisms were identified. The infiltrate lacked atypia, and there was no evidence of hemophagocytosis. The findings were nondiagnostic, and there was no evidence of lymphoma (Figure 2).	
Figure 2 
Dr. Salvi: Intravenous fluids, cryoprecipitate, and empirical cefepime were administered
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 66-year-old man with a history of pancytopenia was transferred to this hospital in the winter for evaluation of pancytopenia and rash.
The patient had been well until 1 year before admission, when episodic fevers began to occur. Approximately 3 months before admission, fevers with a temperature of up to 38.3[degrees]C increased in frequency and severity and coincided with shaking chills. Scattered papules developed on the arms and legs; the lesions were initially deeply erythematous, but over a period of several days, the discoloration faded and the skin sloughed. There was no associated pruritus, and febrile episodes did not coincide with worsening of the skin lesions.
Two months before admission, episodes of orthostatic hypotension and dizziness developed. The patient was admitted to other hospitals on two occasions for recurrent lightheadedness. Laboratory evaluation reportedly revealed a normal level of corticotropin in the blood and a normal increase in the serum cortisol level after intravenous administration of cosyntropin. The white-cell count was 850 per microliter (reference range, 4200 to 9900), the hemoglobin level 9.2 g per deciliter (reference range, 13.0 to 17.4), the platelet count 61,000 per microliter (reference range, 140,000 to 440,000), and the mean corpuscular volume 89 fl (reference range, 82 to 100). The blood levels of aspartate aminotransferase and alanine aminotransferase were elevated. Serologic tests for hepatitis A, B, and C viruses and for human immunodeficiency virus (HIV) type 1 and type 2 were negative. The ferritin level was 12,620 ng per milliliter (reference range, 30 to 400), but subsequent testing for the HFE mutation most often associated with hemochromatosis was negative. Nineteen days before the ferritin level was measured, the iron level was 67 [mu]g per deciliter (12 [mu]mol per liter) (reference range, 45 to 182 [mu]g per deciliter [8 to 33 [mu]mol per liter]), the total iron-binding capacity 143 [mu]g per deciliter (26 [mu]mol per liter) (reference range, 261 to 478 [mu]g per deciliter [47 to 86 [mu]mol per liter]), the transferrin saturation 47% (reference range, 20 to 55), the folate level 18.3 ng per milliliter (41 nmol per liter) (reference range, 6 to 20 ng per milliliter [14 to 45 nmol per liter]), and the vitamin B12 level 861 pg per milliliter (635 pmol per liter) (reference range, 193 to 986 pg per milliliter [142 to 727 pmol per liter]). Magnetic resonance cholangiopancreatography revealed a small amount of pericholecystic fluid and mild edema in the right paracolic gutter that suggested an infiltrative process; the biliary ducts appeared normal, and no intrahepatic iron deposition was seen. The orthostatic hypotension abated, but did not fully resolve, after the administration of intravenous fluids. The patient was discharged home and was instructed to follow up with his primary care physician.
Eight days before admission, orthostatic hypotension recurred. The patient was readmitted to one of the other hospitals, where he reported ongoing lightheadedness and generalized weakness. The temperature was 36.6[degrees]C, the pulse 91 beats per minute, the blood pressure 119/71 mm Hg while the patient was in the supine position (75/48 while he was standing), the respiratory rate 16 breaths per minute, the oxygen saturation 95% while he was breathing ambient air, and the weight 74.9 kg. He was pale, appeared ill, and had marked edema of the legs and periorbital region. Scattered nummular and erosive lesions with overlying eschar were noted on both feet, both forearms, and the medial right thigh; petechiae were also seen on the arms and chest. The remainder of the examination was normal. Laboratory test results are shown in Table 1. An antibody-based screening test for Lyme disease was negative, as were nucleic acid tests for babesia, ehrlichia, anaplasma, adenovirus, and cytomegalovirus. Histoplasma and aspergillus antigens were not detected in the blood. Cultures of the blood were negative.	
Table 1 
A transthoracic echocardiogram was of technically poor quality but showed normal biventricular function; valvular dysfunction was not assessed. Radiography of the chest revealed atelectasis but was otherwise normal. Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, revealed small bilateral pleural effusions and no evidence of lymphadenopathy; CT of the abdomen and pelvis revealed normal hepatic parenchyma, a moderate amount of ascites, mild splenomegaly, and no evidence of lymphadenopathy. Positron-emission tomography (PET) from the skull base to the thighs, performed after the administration of intravenous 18F-fluorodeoxyglucose (FDG) tracer, revealed homogeneous FDG uptake in the spleen, and there was no evidence of hypermetabolism in the abdominal or pelvic lymph nodes.
The patient was transferred to this hospital for further evaluation and management of possible hemophagocytic lymphohistiocytosis (HLH).
Dr. Valentina Nardi: Examination of a bone marrow biopsy specimen and aspirate that were obtained at the other hospital revealed maturing trilineage hematopoiesis and mildly hypercellular marrow with many histiocytes and numerous engulfed erythroid elements in the cytoplasm. The findings were consistent with hemophagocytosis, with no evidence of infection or lymphoma (Figure 1).	
Figure 1
Dr. Kristine M. Cornejo: A punch biopsy of an erythematous lesion on the right thigh was performed at the other hospital. Microscopic examination of the specimen revealed focal epidermal erosion with impetiginized scale crust and a mild lymphohistiocytic infiltrate in the dermis and subcutaneous tissue; no fungal organisms were identified. The infiltrate lacked atypia, and there was no evidence of hemophagocytosis. The findings were nondiagnostic, and there was no evidence of lymphoma (Figure 2).	
Figure 2 
Dr. Salvi: Intravenous fluids, cryoprecipitate, and empirical cefepime were administered
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms include pancytopenia, fevers, rash, and orthostatic hypotension. The patient's lab results show elevated ferritin levels and evidence of hemophagocytosis in the bone marrow. These findings are consistent with hemophagocytic lymphohistiocytosis (HLH), a condition characterized by overactivation of the immune system, leading to severe inflammation and organ damage. The patient's symptoms, lab results, and bone marrow biopsy results all support this diagnosis.\n\nHemophagocytic lymphohistiocytosis (HLH)""
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}",Hemophagocytic lymphohistiocytosis (HLH),N,"{
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        ""content"": ""The patient is a 66-year-old man with a history of pancytopenia who presents with episodic fevers, rash, and orthostatic hypotension. His lab results show elevated liver enzymes and ferritin levels, but negative tests for hepatitis and HIV. He also has negative tests for Lyme disease, babesia, ehrlichia, anaplasma, adenovirus, and cytomegalovirus. His bone marrow biopsy shows evidence of hemophagocytosis, but no evidence of infection or lymphoma. The differential diagnosis for this patient includes hemophagocytic lymphohistiocytosis (HLH), systemic lupus erythematosus (SLE), and lymphoma. The patient's negative tests for various infections and lack of lymphadenopathy make lymphoma less likely. SLE can cause pancytopenia and rash, but it typically does not cause hemophagocytosis. HLH is a condition characterized by overactivation of the immune system, leading to severe inflammation and organ damage. It can cause the symptoms seen in this patient, including fever, rash, pancytopenia, and hemophagocytosis. Therefore, HLH is the most likely diagnosis.\n\nDiagnosis: Hemophagocytic lymphohistiocytosis (HLH)""
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}",Hemophagocytic lymphohistiocytosis (HLH),N
10.1056/NEJMcpc1904047,Case 34-2019: A 16-Year-Old Boy with Jaundice,"Hemoglobin (g/dl)   12.2 13.0–16.0 11.4
Hematocrit (%)  36 37.0–49.0 33.2
White-cell count (per μl) 450 ,000 700 450 ,000 900
Differential count (%)
Neutrophils 20
Lymphocytes 64
Monocytes 8
Atypical lymphocytes 8
Platelet count (per μl)   95,000   92,000
Red-cell count (per μl) 4,090,000  4,030,000
Prothrombin time (sec) 16.1
Prothrombin-time international normalized 
ratio
  1.3
Protein (mg/dl)
Total 6.1–8.2 6.1 6. .3 5.8
Albumin   3.8   4.1
Globulin 2.5–4.3 2.3   1.7
Alanine aminotransferase (U/liter)  3058   2839
Aspartate aminotransferase (U/liter)  1664   1751
Alkaline phosphatase (U/liter)  297  299
γ-Glutamyltransferase (U/liter)  140 8–61 104
Bilirubin (mg/dl)
Total 8.5  8.1
Direct 6.3  5.7
Ceruloplasmin (mg/dl) 20–43 49",B-cell acute lymphoblastic leukemia,Acute leukemia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 16-year-old boy was admitted to this hospital in autumn because of jaundice and abnormal results on liver-function tests.
The patient had been well until 4 days before admission, when he noted pruritus around his ankles. That night, malaise and mild, intermittent, cramping pain in the right upper quadrant developed. The next day, the patient felt fatigued, his appetite was reduced, and the pruritus became diffuse. Two days before admission, he spent much of the day lying on the couch because of fatigue and malaise; he also reported that food tasted ""funny,"" that his urine appeared darker than usual, and that his mother had told him he appeared pale. The day before admission, the patient continued to feel unwell but went to school, where he was told by a teacher that his skin appeared yellow, which prompted him to present to the school nurse. After a discussion with the patient's mother and pediatrician, the patient was referred to the emergency department at another hospital for evaluation.
At the other hospital, the patient reported that his stool had appeared pale gray that day. On examination, the temperature was 36.7[degrees]C, the pulse 102 beats per minute, the blood pressure 139/82 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The patient did not appear ill but had conjunctival icterus and jaundiced skin. There was no abdominal tenderness, and the remainder of the physical examination was normal. The red-cell indexes and blood levels of electrolytes, glucose, amylase, and lipase were normal, as were the results of renal-function tests; other laboratory test results are shown in Table 1. Urinalysis showed clear, amber urine, with a moderate amount of bilirubin, trace albumin, a specific gravity of 1.018, and a pH of 5.5 by dipstick testing. A blood test for heterophile antibodies was negative, as were blood tests for hepatitis A virus IgM antibodies, hepatitis B virus surface antigen, hepatitis B virus core IgM antibodies, and hepatitis C virus antibodies. After discussion with a pediatric gastroenterologist, the patient was transferred to the emergency department of this hospital.	
Table 1
On arrival, the patient rated his abdominal pain at 6 on a scale of 0 to 10, with 10 indicating the most severe pain. He had undergone tonsillectomy in the remote past. He had never received a blood transfusion. He took no medications or herbal or dietary supplements and had no known allergies; immunizations were reportedly up to date. The patient lived with his parents and two dogs in a heavily forested, rural area of New England and had not traveled recently. Five days before the onset of illness, he had eaten at a fast-food restaurant. He had had no known exposure to sick persons, was not sexually active, and did not smoke cigarettes, drink alcohol, or use illicit drugs. One year earlier, the patient's mother had undergone a medical evaluation because of fatigue and jaundice and had been found to have abnormally elevated results of liver-function tests; no specific diagnosis was made, and the illness resolved spontaneously. His maternal grandfather had a history of nonalcoholic fatty liver disease and brain cancer. A maternal second cousin had systemic lupus erythematosus.
On examination, the patient appeared jaundiced but not ill. The temperature was 36.8[degrees]C, the pulse 80 beats per minute, the blood pressure 134/59 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. The weight was 76.5 kg. There was mild tenderness in the right upper quadrant; evaluation for hepatomegaly and splenomegaly was limited because the patient was ticklish. The remainder of the physical examination was unchanged. The red-cell indexes, activated partial-thromboplastin time, anion gap, and blood levels of electrolytes, glucose, lipase, and acetaminophen were normal, as were the results of renal-function tests; other laboratory test results are shown in Table 1. Urinalysis showed clear, amber urine, with 1+ bilirubin, 1+ urobilinogen, a specific gravity of 1.010, and a pH of 6.0 by dipstick testing. Blood was tested for human immunodeficiency virus type 1 RNA, as well as for Epstein-Barr virus (EBV) antibodies, cytomegalovirus antibodies, Borrelia burgdorferi antibodies, antinuclear antibodies, antimitochondrial antibodies, anti-smooth muscle antibodies, and anti-liver-kidney microsomal type 1 antibodies.
Dr. Aoife Kilcoyne: Ultrasonography of the abdomen revealed mild, diffuse heterogeneous echotexture of the liver. No intrahepatic or extrahepatic biliary ductal dilatation was noted. The gallbladder was contracted, with no pericholecystic fluid. There was no ascites. The spleen was enlarged, measuring up to 16.2 cm in the craniocaudal dimension (normal length, <13 cm)1 (Figure 1). No focal splenic lesions were observed. Doppler evaluation of the upper abdominal vasculature was normal.	
Figure 1 
Dr. Gupta: While the patient was in the emergency department, the abdominal pain decreased. Intravenous fluids were administered, and, early the next morning, the patient was admitted to the hospital.
On admission, the patient reported mild, diffuse pruritus, which was most prominent on the upper back, and mild, diffuse abdominal pain. There was no pharyngeal erythema or exudate and no cervical, supraclavicular, axillary, or inguinal lymphadenopathy; the remainder of the physical examination was unchanged. The patient received treatment with oral ursodiol and vitamin E and intramuscular vitamin K.
Additional diagnostic tests were performed, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 16-year-old boy was admitted to this hospital in autumn because of jaundice and abnormal results on liver-function tests.
The patient had been well until 4 days before admission, when he noted pruritus around his ankles. That night, malaise and mild, intermittent, cramping pain in the right upper quadrant developed. The next day, the patient felt fatigued, his appetite was reduced, and the pruritus became diffuse. Two days before admission, he spent much of the day lying on the couch because of fatigue and malaise; he also reported that food tasted ""funny,"" that his urine appeared darker than usual, and that his mother had told him he appeared pale. The day before admission, the patient continued to feel unwell but went to school, where he was told by a teacher that his skin appeared yellow, which prompted him to present to the school nurse. After a discussion with the patient's mother and pediatrician, the patient was referred to the emergency department at another hospital for evaluation.
At the other hospital, the patient reported that his stool had appeared pale gray that day. On examination, the temperature was 36.7[degrees]C, the pulse 102 beats per minute, the blood pressure 139/82 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The patient did not appear ill but had conjunctival icterus and jaundiced skin. There was no abdominal tenderness, and the remainder of the physical examination was normal. The red-cell indexes and blood levels of electrolytes, glucose, amylase, and lipase were normal, as were the results of renal-function tests; other laboratory test results are shown in Table 1. Urinalysis showed clear, amber urine, with a moderate amount of bilirubin, trace albumin, a specific gravity of 1.018, and a pH of 5.5 by dipstick testing. A blood test for heterophile antibodies was negative, as were blood tests for hepatitis A virus IgM antibodies, hepatitis B virus surface antigen, hepatitis B virus core IgM antibodies, and hepatitis C virus antibodies. After discussion with a pediatric gastroenterologist, the patient was transferred to the emergency department of this hospital.	
Table 1
On arrival, the patient rated his abdominal pain at 6 on a scale of 0 to 10, with 10 indicating the most severe pain. He had undergone tonsillectomy in the remote past. He had never received a blood transfusion. He took no medications or herbal or dietary supplements and had no known allergies; immunizations were reportedly up to date. The patient lived with his parents and two dogs in a heavily forested, rural area of New England and had not traveled recently. Five days before the onset of illness, he had eaten at a fast-food restaurant. He had had no known exposure to sick persons, was not sexually active, and did not smoke cigarettes, drink alcohol, or use illicit drugs. One year earlier, the patient's mother had undergone a medical evaluation because of fatigue and jaundice and had been found to have abnormally elevated results of liver-function tests; no specific diagnosis was made, and the illness resolved spontaneously. His maternal grandfather had a history of nonalcoholic fatty liver disease and brain cancer. A maternal second cousin had systemic lupus erythematosus.
On examination, the patient appeared jaundiced but not ill. The temperature was 36.8[degrees]C, the pulse 80 beats per minute, the blood pressure 134/59 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. The weight was 76.5 kg. There was mild tenderness in the right upper quadrant; evaluation for hepatomegaly and splenomegaly was limited because the patient was ticklish. The remainder of the physical examination was unchanged. The red-cell indexes, activated partial-thromboplastin time, anion gap, and blood levels of electrolytes, glucose, lipase, and acetaminophen were normal, as were the results of renal-function tests; other laboratory test results are shown in Table 1. Urinalysis showed clear, amber urine, with 1+ bilirubin, 1+ urobilinogen, a specific gravity of 1.010, and a pH of 6.0 by dipstick testing. Blood was tested for human immunodeficiency virus type 1 RNA, as well as for Epstein-Barr virus (EBV) antibodies, cytomegalovirus antibodies, Borrelia burgdorferi antibodies, antinuclear antibodies, antimitochondrial antibodies, anti-smooth muscle antibodies, and anti-liver-kidney microsomal type 1 antibodies.
Dr. Aoife Kilcoyne: Ultrasonography of the abdomen revealed mild, diffuse heterogeneous echotexture of the liver. No intrahepatic or extrahepatic biliary ductal dilatation was noted. The gallbladder was contracted, with no pericholecystic fluid. There was no ascites. The spleen was enlarged, measuring up to 16.2 cm in the craniocaudal dimension (normal length, <13 cm)1 (Figure 1). No focal splenic lesions were observed. Doppler evaluation of the upper abdominal vasculature was normal.	
Figure 1 
Dr. Gupta: While the patient was in the emergency department, the abdominal pain decreased. Intravenous fluids were administered, and, early the next morning, the patient was admitted to the hospital.
On admission, the patient reported mild, diffuse pruritus, which was most prominent on the upper back, and mild, diffuse abdominal pain. There was no pharyngeal erythema or exudate and no cervical, supraclavicular, axillary, or inguinal lymphadenopathy; the remainder of the physical examination was unchanged. The patient received treatment with oral ursodiol and vitamin E and intramuscular vitamin K.
Additional diagnostic tests were performed, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of jaundice, pruritus, fatigue, malaise, and abnormal liver-function tests suggest a liver disorder. The patient's history of eating at a fast-food restaurant five days before the onset of illness raises the possibility of a foodborne illness, such as hepatitis A, but tests for hepatitis A, B, and C were all negative. The patient's mother had a similar illness a year ago that resolved spontaneously, suggesting a possible genetic or environmental factor. The patient's abdominal ultrasound showed mild, diffuse heterogeneous echotexture of the liver and an enlarged spleen, but no other abnormalities. The patient's symptoms and test results do not fit the typical presentation of common liver diseases such as hepatitis, cirrhosis, or liver cancer. However, they are consistent with autoimmune hepatitis, a disease in which the body's immune system attacks liver cells. This diagnosis is supported by the patient's family history of autoimmune disease (a second cousin with systemic lupus erythematosus) and the fact that the patient's symptoms improved with treatment with ursodiol and vitamins E and K, which are used to treat autoimmune hepatitis.\n\nDiagnosis: Autoimmune Hepatitis.""
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        ""content"": ""The patient's symptoms of jaundice, pruritus, fatigue, malaise, and abdominal pain, along with abnormal liver function tests, suggest a liver disorder. The presence of bilirubin in the urine indicates that the liver is producing bilirubin, but it is not being properly excreted, which is consistent with obstructive jaundice. However, the ultrasound did not show any biliary ductal dilatation, which would be expected in obstructive jaundice. The patient's history of eating at a fast-food restaurant could suggest a foodborne illness, but the negative tests for hepatitis A, B, and C make this less likely. The patient's mother's history of a similar illness that resolved spontaneously could suggest a genetic or autoimmune condition. The absence of hepatomegaly and splenomegaly on examination, along with the normal Doppler evaluation of the upper abdominal vasculature, makes cirrhosis or portal hypertension unlikely. The patient's symptoms and test results are most consistent with an autoimmune hepatitis.\n\nDiagnosis: Autoimmune Hepatitis.""
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        ""content"": ""The patient is a 16-year-old boy presenting with jaundice, pruritus, malaise, fatigue, and right upper quadrant pain. He also reports that his urine is darker than usual and his stool is pale gray. These symptoms suggest a liver disorder. The differential diagnosis includes viral hepatitis, autoimmune hepatitis, drug-induced liver injury, and Wilson's disease. The patient's blood tests for hepatitis A, B, and C were all negative, ruling out viral hepatitis. The patient does not take any medications or supplements, making drug-induced liver injury less likely. Wilson's disease typically presents with neurological symptoms, which this patient does not have. Autoimmune hepatitis is a possibility, especially given the family history of autoimmune disease (a second cousin with systemic lupus erythematosus). The patient's mother also had a similar episode of jaundice and fatigue that resolved spontaneously, which could suggest a genetic or familial condition. The patient's liver function tests are significantly elevated, which is consistent with a hepatocellular pattern of liver injury, often seen in autoimmune hepatitis. The patient's ANA, anti-smooth muscle, and anti-liver kidney microsomal type 1 antibodies were tested, which are typically elevated in autoimmune hepatitis. \n\nDiagnosis: Autoimmune Hepatitis.""
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}",Autoimmune Hepatitis,N
10.1056/NEJMcpc1904046,Case 33-2019: A 35-Year-Old Woman with Cardiopulmonary Arrest during Cesarean Section,"Hematocrit (%)   35.4 28.9
Hemoglobin (g/dl)   11.3 9.2
White-cell count (per mm3
)   10,080 12,300
Platelet count (per mm3
)   203,000 64,000
Red-cell count (per mm3
) 4,000,000–5,200,000 4,520,000 3,710,000
Mean corpuscular volume (fl)   78.3 77.9
Mean corpuscular hemoglobin (pg) 26. 4.0 25.0 24.8
Mean corpuscular hemoglobin concentration (g/dl) 31. 7.0 31.9 31.8
Red-cell distribution width (%)   14.6 15.1
Prothrombin time (sec)   13.4 18.0
Prothrombin-time international normalized ratio   1.0 1.5
Partial-thromboplastin time (sec) 22. 5.0 29.1 >150.0
Fibrinogen (mg/dl) 15 0 411 81
Glucose (mg/dl) 6 9 80 148
Calcium (mg/dl) 8.9–10.3 8.9
Ionized calcium (mmol/liter)   0.72
Lactate (mmol/liter)   7.3
Arterial pH   7.21
Arterial partial pressure of carbon dioxide (mm Hg)   39
Arterial partial pressure of oxygen (mm Hg)   254",Amniotic fluid embolism,Amniotic fluid embolism,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 35-year-old pregnant woman was admitted to the labor and delivery unit of this hospital at 36 weeks 4 days of gestation for a planned repeat cesarean section because of placenta previa.
At 6 weeks 4 days of gestation, the patient had been seen at a community health center because of a positive pregnancy test. She was gravida 4, 1-0-2-1. Her first pregnancy, 5 years earlier, had resulted in the need for a cesarean section because the fetus was in the breech presentation; the baby was delivered at full term without complications. The second and third pregnancies had been electively terminated. The patient reported that her husband had human immunodeficiency virus type 1 (HIV-1) infection and that he had been taking antiretroviral therapy; he had had undetectable plasma levels of HIV-1 RNA during the 5 months before this visit. Blood testing in the patient for HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen with the use of a fourth-generation combination assay was negative. Preexposure prophylaxis with a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate was prescribed.
The patient continued to receive routine prenatal care at the community health center. At 16 weeks 5 days of gestation, the result of an oral glucose tolerance test was abnormal, and a diagnosis of gestational diabetes mellitus was made. Dietary modifications, exercise, and fingerstick glucose monitoring were prescribed. Obstetrical ultrasonography with fetal survey performed at 18 weeks 4 days of gestation revealed a placenta that was positioned anteriorly, with complete placenta previa. The results of all other prenatal screening tests were normal. The blood type was O, Rh-positive, with negative antibody testing. The patient was advised not to have sexual intercourse and to seek immediate medical attention if vaginal bleeding were to occur. She was informed that a cesarean delivery would be scheduled to occur between 36 and 37 weeks of gestation.
Twenty-five days before presentation, at 33 weeks of gestation, vaginal bleeding developed, and the patient was brought by ambulance to the obstetrical unit of this hospital. She reported that on awakening that morning, she had passed a large volume of bright red, liquid blood and three large clots, each measuring approximately 1.5 cm in diameter, through the vagina. She felt occasional contractions; fetal movement was normal. She reported no recent trauma, fall, or sexual intercourse. On examination, the patient appeared well. The pulse was 112 beats per minute, and other vital signs were normal. The abdomen was gravid, soft, and nontender. A speculum examination revealed a closed cervical os, a small amount of bright red blood, and no pooling fluid. The hemoglobin level was 11.5 g per deciliter (reference range, 12.0 to 16.0), and the hematocrit was 35.0% (reference range, 36.0 to 46.0). On a nonstress test, the fetal heart rate was 140 beats per minute, with moderate variability, accelerations, and a single deceleration with a rapid return to baseline.
Ultrasonographic examination was performed; the placenta was positioned anteriorly along the midline of the uterus, completely overlying the cervical os, and there was no evidence of placenta accreta. The measurements of the fetus were appropriate for gestational age, with a biophysical profile score of 8/8 (indicating normal fetal well-being).
The patient was admitted to the labor and delivery unit for observation. External tocodynamometry showed uterine irritability; magnesium, betamethasone, and penicillin were administered, but the contractions persisted. After she received additional treatment with oral nifedipine, the contractions stopped. No additional vaginal bleeding occurred, and the hemoglobin level and hematocrit remained stable. Postprandial hyperglycemia was noted, and a regimen of subcutaneous insulin was initiated. The patient was discharged home on the fifth hospital day.
Two days after discharge, at 33 weeks 6 days of gestation, unprovoked vaginal bleeding recurred, and the patient was transported by ambulance to the emergency department at another hospital. She reported copious bright red vaginal bleeding, with several large clots, and pelvic cramping; fetal movement was normal. On examination, the patient appeared well, and the vital signs were normal. The abdomen was gravid and soft, with mild tenderness on palpation at the fundus. A speculum examination revealed a closed cervix and approximately 5 ml of dark brown blood in the vaginal vault, with no ongoing bleeding through the os. The patient was transferred by ambulance to the antepartum care unit of this hospital; the fetal heart rate was 145 beats per minute, with moderate variability and accelerations and without decelerations. Laboratory test results are shown in Table 1. The patient was observed for 4 days; she had no contractions or further vaginal bleeding. On the third hospital day, she was discharged home, and a cesarean section was scheduled for 36 weeks 4 days of gestation.	
Table 1 
On admission for the scheduled cesarean delivery, the patient reported feeling well, with no abdominal pain, contractions, or recurrent vaginal bleeding. She was obese and had a history of sciatica, for which she had undergone lumbar laminectomy in the remote past. Medications included prenatal vitamins and subcutaneous insulin. She had no known allergies. The patient had been born in southeastern Africa and lived in New England. She was monogamous with her husband and did not smoke tobacco, drink alcohol, or use illicit substances. The family medical history was unknown.
That afternoon, the patient underwent cesarean section under combined spinal-epidural anesthesia. Cefazolin was administered intravenously before incision of the skin. During the surgery, a low transverse uterine incision was made through the anterior placenta. The membranes were ruptured bluntly, yielding clear amniotic fluid. The uterine incision was extended, and the infant was delivered 37 minutes after injection of the spinal anesthetic agent, which was administered during a combined spinal-epidural procedure; the opaque surgical drape was lowered, allowing the patient to see the infant through the clear drape. The 1-minute and 5-minute Apgar scores were 8 and 10, respectively. The placenta was removed with gentle traction.
Three minutes after delivery of the infant, while clot and debris were being cleared from the uterine cavity, the exteriorized uterus became blanched with minimal bleeding. Concurrently, the patient was noted to be unresponsive, with sporadic respirations; carotid and aortic pulses were present. Manual ventilation was begun. Two minutes later, the patient became pulseless, with normal sinus rhythm seen on the patient monitor of the anesthesia machine. Cardiopulmonary resuscitation was begun, the trachea was intubated, and mechanical ventilation was initiated.
Thirty-eight minutes after delivery of the infant, generalized bleeding and oozing began, with blood and debris emanating from the surgical incision and spreading throughout the operative field. Laboratory test results are shown in Table 1.
A diagnosis and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 35-year-old pregnant woman was admitted to the labor and delivery unit of this hospital at 36 weeks 4 days of gestation for a planned repeat cesarean section because of placenta previa.
At 6 weeks 4 days of gestation, the patient had been seen at a community health center because of a positive pregnancy test. She was gravida 4, 1-0-2-1. Her first pregnancy, 5 years earlier, had resulted in the need for a cesarean section because the fetus was in the breech presentation; the baby was delivered at full term without complications. The second and third pregnancies had been electively terminated. The patient reported that her husband had human immunodeficiency virus type 1 (HIV-1) infection and that he had been taking antiretroviral therapy; he had had undetectable plasma levels of HIV-1 RNA during the 5 months before this visit. Blood testing in the patient for HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen with the use of a fourth-generation combination assay was negative. Preexposure prophylaxis with a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate was prescribed.
The patient continued to receive routine prenatal care at the community health center. At 16 weeks 5 days of gestation, the result of an oral glucose tolerance test was abnormal, and a diagnosis of gestational diabetes mellitus was made. Dietary modifications, exercise, and fingerstick glucose monitoring were prescribed. Obstetrical ultrasonography with fetal survey performed at 18 weeks 4 days of gestation revealed a placenta that was positioned anteriorly, with complete placenta previa. The results of all other prenatal screening tests were normal. The blood type was O, Rh-positive, with negative antibody testing. The patient was advised not to have sexual intercourse and to seek immediate medical attention if vaginal bleeding were to occur. She was informed that a cesarean delivery would be scheduled to occur between 36 and 37 weeks of gestation.
Twenty-five days before presentation, at 33 weeks of gestation, vaginal bleeding developed, and the patient was brought by ambulance to the obstetrical unit of this hospital. She reported that on awakening that morning, she had passed a large volume of bright red, liquid blood and three large clots, each measuring approximately 1.5 cm in diameter, through the vagina. She felt occasional contractions; fetal movement was normal. She reported no recent trauma, fall, or sexual intercourse. On examination, the patient appeared well. The pulse was 112 beats per minute, and other vital signs were normal. The abdomen was gravid, soft, and nontender. A speculum examination revealed a closed cervical os, a small amount of bright red blood, and no pooling fluid. The hemoglobin level was 11.5 g per deciliter (reference range, 12.0 to 16.0), and the hematocrit was 35.0% (reference range, 36.0 to 46.0). On a nonstress test, the fetal heart rate was 140 beats per minute, with moderate variability, accelerations, and a single deceleration with a rapid return to baseline.
Ultrasonographic examination was performed; the placenta was positioned anteriorly along the midline of the uterus, completely overlying the cervical os, and there was no evidence of placenta accreta. The measurements of the fetus were appropriate for gestational age, with a biophysical profile score of 8/8 (indicating normal fetal well-being).
The patient was admitted to the labor and delivery unit for observation. External tocodynamometry showed uterine irritability; magnesium, betamethasone, and penicillin were administered, but the contractions persisted. After she received additional treatment with oral nifedipine, the contractions stopped. No additional vaginal bleeding occurred, and the hemoglobin level and hematocrit remained stable. Postprandial hyperglycemia was noted, and a regimen of subcutaneous insulin was initiated. The patient was discharged home on the fifth hospital day.
Two days after discharge, at 33 weeks 6 days of gestation, unprovoked vaginal bleeding recurred, and the patient was transported by ambulance to the emergency department at another hospital. She reported copious bright red vaginal bleeding, with several large clots, and pelvic cramping; fetal movement was normal. On examination, the patient appeared well, and the vital signs were normal. The abdomen was gravid and soft, with mild tenderness on palpation at the fundus. A speculum examination revealed a closed cervix and approximately 5 ml of dark brown blood in the vaginal vault, with no ongoing bleeding through the os. The patient was transferred by ambulance to the antepartum care unit of this hospital; the fetal heart rate was 145 beats per minute, with moderate variability and accelerations and without decelerations. Laboratory test results are shown in Table 1. The patient was observed for 4 days; she had no contractions or further vaginal bleeding. On the third hospital day, she was discharged home, and a cesarean section was scheduled for 36 weeks 4 days of gestation.	
Table 1 
On admission for the scheduled cesarean delivery, the patient reported feeling well, with no abdominal pain, contractions, or recurrent vaginal bleeding. She was obese and had a history of sciatica, for which she had undergone lumbar laminectomy in the remote past. Medications included prenatal vitamins and subcutaneous insulin. She had no known allergies. The patient had been born in southeastern Africa and lived in New England. She was monogamous with her husband and did not smoke tobacco, drink alcohol, or use illicit substances. The family medical history was unknown.
That afternoon, the patient underwent cesarean section under combined spinal-epidural anesthesia. Cefazolin was administered intravenously before incision of the skin. During the surgery, a low transverse uterine incision was made through the anterior placenta. The membranes were ruptured bluntly, yielding clear amniotic fluid. The uterine incision was extended, and the infant was delivered 37 minutes after injection of the spinal anesthetic agent, which was administered during a combined spinal-epidural procedure; the opaque surgical drape was lowered, allowing the patient to see the infant through the clear drape. The 1-minute and 5-minute Apgar scores were 8 and 10, respectively. The placenta was removed with gentle traction.
Three minutes after delivery of the infant, while clot and debris were being cleared from the uterine cavity, the exteriorized uterus became blanched with minimal bleeding. Concurrently, the patient was noted to be unresponsive, with sporadic respirations; carotid and aortic pulses were present. Manual ventilation was begun. Two minutes later, the patient became pulseless, with normal sinus rhythm seen on the patient monitor of the anesthesia machine. Cardiopulmonary resuscitation was begun, the trachea was intubated, and mechanical ventilation was initiated.
Thirty-eight minutes after delivery of the infant, generalized bleeding and oozing began, with blood and debris emanating from the surgical incision and spreading throughout the operative field. Laboratory test results are shown in Table 1.
A diagnosis and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Amniotic fluid embolism. \n\nThis patient presented with sudden cardiovascular collapse and coagulopathy immediately after delivery, which is highly suggestive of amniotic fluid embolism. This condition is a rare but severe complication of pregnancy. The onset is typically sudden and occurs during labor, during the immediate postpartum period, or during or after a cesarean section or an abortion. The classic presentation includes the sudden onset of cardiovascular collapse and disseminated intravascular coagulation. Other potential causes of sudden cardiovascular collapse in the peripartum period, such as pulmonary embolism, myocardial infarction, or severe hemorrhage, are less likely given the patient's clinical presentation and the timing of her symptoms.""
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}",Amniotic fluid embolism,Y
10.1056/NEJMcpc1909624,"Case 32-2019: A 70-Year-Old Woman with Rapidly Progressive Ataxia
C","Hemoglobin (g/dl)   12.1
Hematocrit (%)   37.3
White-cell count (per mm3)   6390
Differential count (%)
Neutrophils   60.6
Lymphocytes   26.4
Monocytes   9.7
Eosinophils   2.3
Basophils   0.8
Immature granulocytes   0.2
Thyrotropin (μIU/ml) 0.4 0 4.51
Thyroid peroxidase antibodies (IU/ml) <9 260
Thyroglobulin antibodies (IU/ml) <4.0 29
Cerebrospinal fluid
Color Colorless Colorless
Turbidity Clear Clear
Glucose (mg/dl) 50–75 66
Total protein (mg/dl) 5–55 33
Red-cell count (per mm3
) 0–5 1
Total nucleated cells (per mm3)  1
Differential count (%)
Segmented neutrophils 0 0
Lymphocytes  59
Monocytes  41
Xanthochromia Not present Not present",Creutzfeldt‚Äö√Ñ√¨Jakob disease,Cerebellar form of Creutzfeldt–Jakob disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old woman was admitted to this hospital because of rapidly progressive ataxia.
The patient had been in her usual state of good health until 3 months before this admission, when fatigue and general unsteadiness developed. Two months before admission, episodes of worsening unsteadiness occurred. The patient was no longer able to walk in a straight line or to remain stable in yoga poses that had previously been easy for her. No associated falls, vertigo, loss of consciousness, ear pain, hearing loss, tinnitus, or headache were reported. She was evaluated by her primary care physician, who was affiliated with another hospital, and a neurologic examination was reportedly normal. The white-cell count, hematocrit, hemoglobin level, and blood levels of electrolytes, glucose, and thyrotropin were normal, as were the results of kidney-function and liver-function tests; a test for Lyme disease was negative. The patient was referred to an otolaryngologist.
Seven weeks before admission, the patient was evaluated by an otolaryngologist at the other hospital. The examination revealed auditory canals and tympanic membranes that were normal in appearance; an audiogram showed normal hearing. The patient was told that her symptoms were not caused by a vestibular process, and she was referred to a neurologist.
Four weeks before admission, progressive gait imbalance developed. The patient was able to walk in her home without falling by leaning on walls and surfaces for support, but she needed a cane or the assistance of her husband to walk outside. She was evaluated in a neurology clinic at the other hospital. She reported a sensation of impaired balance that persisted when she was seated in a chair and diminished, but did not resolve, when she was in the supine position. She also noted a loss of coordination in her hands; her handwriting had progressively become larger, and she had difficulty eating soup. She reported new blurry vision, insomnia, and a constant mild headache.
On examination, the patient was awake, alert, and oriented. Her speech was fluent and clear. A slightly wide-based, unsteady gait was noted, with jerking movements of the trunk, hips, and legs. She was unable to walk with a tandem gait or on her toes or heels. The Romberg sign was present, and a subtle postural tremor in both hands was noted. The remainder of her neurologic examination was normal. Antinuclear antibodies were present at a titer of 1:40 with a speckled pattern. Blood levels of folate, thiamine, cyanocobalamin (vitamin B12), vitamin E, vitamin B6, and C-reactive protein were normal, as was the erythrocyte sedimentation rate. Results of serum protein electrophoresis were also normal. A screening test for syphilis was negative.
Dr. Bradley R. Buchbinder: Magnetic resonance imaging (MRI) of the head was performed before and after the administration of intravenous contrast material. T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging showed minimal, confluent periventricular signal hyperintensity and scattered focal subcortical signal hyperintensity in both cerebral hemispheres, with mild ventricular prominence (Figure 1).	
Figure 1
Dr. Song: The patient was advised to undergo physical therapy for balance training. Two weeks before admission, sudden and involuntary movements of the arms developed that were associated with loss of positional awareness. The patient sought a second opinion from an otolaryngologist at this hospital, who referred her to the emergency department; she was admitted to the neurology service for further evaluation. She reported ongoing involuntary movements of the arms and loss of positional awareness. Her husband reported that she would often place her coffee cup on a table with excessive force or drop it several inches above the surface. She now required a walker and had had two falls resulting from loss of balance. She also noted new horizontal double vision, decreased appetite, weight loss of approximately 2 to 3 kg in the past month, and a cough.
The patient was right-handed. She had a history of hyperlipidemia, impaired glucose tolerance, and asthma and a long history of mild hearing loss. Medications included simvastatin, vaginal estrogen, and, as needed, lorazepam for insomnia. She had no known medication allergies.
The patient was a retired educator and lived with her husband in New England. She had traveled extensively in the eastern United States and in Western Europe. She had previously participated in daily aerobics, yoga, and dance classes. She had consumed one glass of wine nightly but stopped when her symptoms began. She did not smoke tobacco or use illicit drugs. Her mother had hypertension, and her father had died from lung cancer; her brother and two adult children were healthy. There was no family history of ataxia, dementia, autoimmune disease, or neurodegenerative disease.
On examination, the patient was alert, oriented, and interactive. The temperature was 36.1[degrees]C, the pulse 71 beats per minute, the blood pressure 143/94 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The neck was supple, and she did not have thyromegaly or thyroid nodules. The speech was fluent, with no dysarthria. She had marked dysmetria bilaterally on finger-to-nose and heel-to-shin testing; severe dysdiadochokinesia (i.e., an impaired ability to perform rapid alternating movements) was also noted. The gait was wide-based and unsteady, with truncal ataxia. The remainder of the examination was normal, including repetition and naming, strength, deep-tendon and plantar reflexes, and sensory function. Blood levels of electrolytes, glucose, arsenic, lead, mercury, and cadmium were normal, as were the results of kidney-function testing and urine toxicologic screening. A lumbar puncture was performed, and tests for paraneoplastic antibodies in the blood and cerebrospinal fluid (CSF) were negative. Other laboratory test results and the results of the CSF analysis are shown in Table 1. An MRI of the head was obtained and was interpreted as unchanged from the study obtained 1 month earlier.	
Table 1 
An electroencephalogram (EEG) showed a single sharp wave in the left parietal region but was otherwise normal. Combined positron-emission tomography and computed tomography (PET-CT) from the skull base to midthigh, performed after the administration of intravenous 18F-fluorodeoxyglucose (FDG) tracer, revealed no abnormal FDG uptake. A working diagnosis of autoimmune cerebellitis was made, and intravenous immune globulin was administered. The patient was discharged home on the sixth hospital day, with a plan to follow up in the ataxia unit of this hospital.
Three weeks after discharge, the patient was evaluated in the ataxia unit. Her gait and coordination had worsened; she could no longer ambulate independently with a walker and required one-person assistance. New dysarthria had developed, along with short-term memory loss; she began to forget conversations held earlier in the day. Oculomotor examination revealed occasional square-wave jerks in the primary position (i.e., inappropriate saccades that take the eyes off the target when a person is looking forward, followed by a corrective saccade that brings the eyes back to the target), slowed pursuit movements with frequent saccadic intrusions, hypermetric and hypometric saccades, and mild gaze-evoked nystagmus in the horizontal plane. Her dysarthria was mild but became worse when she attempted to recite consonants rapidly. On finger-to-nose testing, there was bilateral end-point dysmetria with oscillating movements at the elbows, overshoot during rapid finger movements, and dysdiadochokinesia. On heel-to-shin testing, the patient had jerking movements of the shins in the axis, with occasional superimposed lateral movements that occurred more frequently on the left side than on the right side. Rapid tapping of the heels on the ground was dysrhythmic. The gait was profoundly impaired; it was wide-based and unstable, and there was marked titubation of the trunk. The patient required maximal one-person assistance. She was unable to spontaneously recall a list of five words learned a few minutes earlier, and her recall did not improve even after she was provided a category clue or a list of multiple-choice answers. Her score on the Montreal Cognitive Assessment was 15 on a scale of 0 to 30, with a score of less than 25 indicating cognitive impairment and lower scores indicating greater cognitive impairment.
The patient was readmitted to the neurology service of this hospital, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old woman was admitted to this hospital because of rapidly progressive ataxia.
The patient had been in her usual state of good health until 3 months before this admission, when fatigue and general unsteadiness developed. Two months before admission, episodes of worsening unsteadiness occurred. The patient was no longer able to walk in a straight line or to remain stable in yoga poses that had previously been easy for her. No associated falls, vertigo, loss of consciousness, ear pain, hearing loss, tinnitus, or headache were reported. She was evaluated by her primary care physician, who was affiliated with another hospital, and a neurologic examination was reportedly normal. The white-cell count, hematocrit, hemoglobin level, and blood levels of electrolytes, glucose, and thyrotropin were normal, as were the results of kidney-function and liver-function tests; a test for Lyme disease was negative. The patient was referred to an otolaryngologist.
Seven weeks before admission, the patient was evaluated by an otolaryngologist at the other hospital. The examination revealed auditory canals and tympanic membranes that were normal in appearance; an audiogram showed normal hearing. The patient was told that her symptoms were not caused by a vestibular process, and she was referred to a neurologist.
Four weeks before admission, progressive gait imbalance developed. The patient was able to walk in her home without falling by leaning on walls and surfaces for support, but she needed a cane or the assistance of her husband to walk outside. She was evaluated in a neurology clinic at the other hospital. She reported a sensation of impaired balance that persisted when she was seated in a chair and diminished, but did not resolve, when she was in the supine position. She also noted a loss of coordination in her hands; her handwriting had progressively become larger, and she had difficulty eating soup. She reported new blurry vision, insomnia, and a constant mild headache.
On examination, the patient was awake, alert, and oriented. Her speech was fluent and clear. A slightly wide-based, unsteady gait was noted, with jerking movements of the trunk, hips, and legs. She was unable to walk with a tandem gait or on her toes or heels. The Romberg sign was present, and a subtle postural tremor in both hands was noted. The remainder of her neurologic examination was normal. Antinuclear antibodies were present at a titer of 1:40 with a speckled pattern. Blood levels of folate, thiamine, cyanocobalamin (vitamin B12), vitamin E, vitamin B6, and C-reactive protein were normal, as was the erythrocyte sedimentation rate. Results of serum protein electrophoresis were also normal. A screening test for syphilis was negative.
Dr. Bradley R. Buchbinder: Magnetic resonance imaging (MRI) of the head was performed before and after the administration of intravenous contrast material. T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging showed minimal, confluent periventricular signal hyperintensity and scattered focal subcortical signal hyperintensity in both cerebral hemispheres, with mild ventricular prominence (Figure 1).	
Figure 1
Dr. Song: The patient was advised to undergo physical therapy for balance training. Two weeks before admission, sudden and involuntary movements of the arms developed that were associated with loss of positional awareness. The patient sought a second opinion from an otolaryngologist at this hospital, who referred her to the emergency department; she was admitted to the neurology service for further evaluation. She reported ongoing involuntary movements of the arms and loss of positional awareness. Her husband reported that she would often place her coffee cup on a table with excessive force or drop it several inches above the surface. She now required a walker and had had two falls resulting from loss of balance. She also noted new horizontal double vision, decreased appetite, weight loss of approximately 2 to 3 kg in the past month, and a cough.
The patient was right-handed. She had a history of hyperlipidemia, impaired glucose tolerance, and asthma and a long history of mild hearing loss. Medications included simvastatin, vaginal estrogen, and, as needed, lorazepam for insomnia. She had no known medication allergies.
The patient was a retired educator and lived with her husband in New England. She had traveled extensively in the eastern United States and in Western Europe. She had previously participated in daily aerobics, yoga, and dance classes. She had consumed one glass of wine nightly but stopped when her symptoms began. She did not smoke tobacco or use illicit drugs. Her mother had hypertension, and her father had died from lung cancer; her brother and two adult children were healthy. There was no family history of ataxia, dementia, autoimmune disease, or neurodegenerative disease.
On examination, the patient was alert, oriented, and interactive. The temperature was 36.1[degrees]C, the pulse 71 beats per minute, the blood pressure 143/94 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The neck was supple, and she did not have thyromegaly or thyroid nodules. The speech was fluent, with no dysarthria. She had marked dysmetria bilaterally on finger-to-nose and heel-to-shin testing; severe dysdiadochokinesia (i.e., an impaired ability to perform rapid alternating movements) was also noted. The gait was wide-based and unsteady, with truncal ataxia. The remainder of the examination was normal, including repetition and naming, strength, deep-tendon and plantar reflexes, and sensory function. Blood levels of electrolytes, glucose, arsenic, lead, mercury, and cadmium were normal, as were the results of kidney-function testing and urine toxicologic screening. A lumbar puncture was performed, and tests for paraneoplastic antibodies in the blood and cerebrospinal fluid (CSF) were negative. Other laboratory test results and the results of the CSF analysis are shown in Table 1. An MRI of the head was obtained and was interpreted as unchanged from the study obtained 1 month earlier.	
Table 1 
An electroencephalogram (EEG) showed a single sharp wave in the left parietal region but was otherwise normal. Combined positron-emission tomography and computed tomography (PET-CT) from the skull base to midthigh, performed after the administration of intravenous 18F-fluorodeoxyglucose (FDG) tracer, revealed no abnormal FDG uptake. A working diagnosis of autoimmune cerebellitis was made, and intravenous immune globulin was administered. The patient was discharged home on the sixth hospital day, with a plan to follow up in the ataxia unit of this hospital.
Three weeks after discharge, the patient was evaluated in the ataxia unit. Her gait and coordination had worsened; she could no longer ambulate independently with a walker and required one-person assistance. New dysarthria had developed, along with short-term memory loss; she began to forget conversations held earlier in the day. Oculomotor examination revealed occasional square-wave jerks in the primary position (i.e., inappropriate saccades that take the eyes off the target when a person is looking forward, followed by a corrective saccade that brings the eyes back to the target), slowed pursuit movements with frequent saccadic intrusions, hypermetric and hypometric saccades, and mild gaze-evoked nystagmus in the horizontal plane. Her dysarthria was mild but became worse when she attempted to recite consonants rapidly. On finger-to-nose testing, there was bilateral end-point dysmetria with oscillating movements at the elbows, overshoot during rapid finger movements, and dysdiadochokinesia. On heel-to-shin testing, the patient had jerking movements of the shins in the axis, with occasional superimposed lateral movements that occurred more frequently on the left side than on the right side. Rapid tapping of the heels on the ground was dysrhythmic. The gait was profoundly impaired; it was wide-based and unstable, and there was marked titubation of the trunk. The patient required maximal one-person assistance. She was unable to spontaneously recall a list of five words learned a few minutes earlier, and her recall did not improve even after she was provided a category clue or a list of multiple-choice answers. Her score on the Montreal Cognitive Assessment was 15 on a scale of 0 to 30, with a score of less than 25 indicating cognitive impairment and lower scores indicating greater cognitive impairment.
The patient was readmitted to the neurology service of this hospital, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms include rapidly progressive ataxia, dysmetria, dysdiadochokinesia, and cognitive impairment. These symptoms suggest a neurological disorder. The patient's MRI showed minimal, confluent periventricular signal hyperintensity and scattered focal subcortical signal hyperintensity in both cerebral hemispheres, which could be indicative of a neurodegenerative disease. The patient's symptoms did not improve with intravenous immune globulin, which suggests that the condition is not autoimmune in nature. The patient's symptoms and the MRI findings are consistent with Creutzfeldt-Jakob disease (CJD), a rare, degenerative, invariably fatal brain disorder. \n\nDiagnosis: Creutzfeldt-Jakob disease.""
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        ""content"": ""The patient's symptoms include rapidly progressive ataxia, dysmetria, dysdiadochokinesia, and cognitive impairment. These symptoms suggest a neurological disorder. The MRI of the head showed minimal, confluent periventricular signal hyperintensity and scattered focal subcortical signal hyperintensity in both cerebral hemispheres, which could be indicative of a degenerative brain disease. The patient's age also supports a diagnosis of a degenerative disease. The patient's symptoms did not improve with intravenous immune globulin, which suggests that the condition is not autoimmune in nature. The patient's symptoms and the results of the MRI are consistent with a diagnosis of Creutzfeldt-Jakob disease (CJD), a rare and fatal degenerative brain disorder.\n\nDiagnosis: Creutzfeldt-Jakob disease.""
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        ""content"": ""The patient is a 70-year-old woman presenting with rapidly progressive ataxia, dysmetria, dysdiadochokinesia, and cognitive impairment. The differential diagnosis for these symptoms includes cerebellar stroke, multiple sclerosis, paraneoplastic cerebellar degeneration, and Creutzfeldt-Jakob disease. Given the patient's age, cerebellar stroke could be a possibility, but the absence of other stroke symptoms and the progressive nature of her symptoms over several weeks make this less likely. Multiple sclerosis typically presents in younger patients and would likely show characteristic lesions on MRI, which were not present in this case. Paraneoplastic cerebellar degeneration is associated with cancer, but the patient's PET-CT scan did not show any abnormal uptake suggestive of malignancy. Creutzfeldt-Jakob disease (CJD), a prion disease, can present with rapidly progressive ataxia and cognitive impairment. The patient's age, the rapid progression of her symptoms, and the absence of an alternative diagnosis make CJD a likely diagnosis. \n\nDiagnosis: Creutzfeldt-Jakob disease.""
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10.1056/NEJMcpc1904045,Case 31-2019: A 45-Year-Old Woman with Headache and Somnolence,"White-cell count (per mm3
) 400 ,000 6490 8450   5710
Platelet count (per mm3
) 135,00 0,000 260,000 166,000   93,000
Differential count (%)
Neutrophils 59.8 71.3   68.1
Lymphocytes  26.8 17.3   20.0
Monocytes  10.9 9.2   7.5
Eosinophils  0.5 0.4   1.9
Basophils  0.8 0.7   0.7
Immature granulocytes   1.2 1.1   1.8
Lactate dehydrogenase (U/liter) 12 46 304 11 10 424
Erythrocyte sedimentation rate (mm/hr)  5
C-reactive protein (mg/liter)  48.5  .0 47.3
Procalcitonin (ng/ml) 0.07
Cerebrospinal fluid
Color Colorless Colorless Colorless Yellow
Turbidity Clear Clear Clear Slight
Glucose (mg/dl)   45  107
Total protein (mg/dl) 190 572
Red-cell count (per mm3) 68
White-cell count (per mm3
) 63 298
Differential count (%)
Segmented neutrophils 18 0 13
Lymphocytes 46 64
Macrophages 36  18
Xanthochromia Not present Not present Not present Present",Adenovirus (serotype 2) meningoencephalitis.,Adenovirus meningoencephalitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 45-year-old woman with multiple sclerosis, seronegative inflammatory polyarthritis, and migraine was admitted to this hospital during the winter because of lethargy and decreased verbal output.
The patient had been in her usual state of health until 13 days before this admission, when a severe headache developed. The pain began insidiously, was pounding in quality, and radiated from the occiput to the retro-orbital area and forehead. The onset of pain coincided with visual aura, including blurring of the peripheral vision and oscillating flashes of light. The headache was reminiscent of the patient's previous migraine headaches, the last of which had occurred more than 10 years earlier; symptoms had typically abated with butalbital-acetaminophen-caffeine therapy.
Five days later, and 8 days before this admission, symptoms worsened, and the patient sought care at the emergency department at another hospital. On arrival, she reported photophobia, nausea, and vomiting; she had no history of head injury, and she reported no neck pain, fever, chills, numbness, tingling, weakness, or dizziness. On examination, the temperature was 37.1[degrees]C, the pulse 101 beats per minute, the blood pressure 147/98 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. She appeared uncomfortable and was lying in bed in a dark room with her eyes covered. She was alert, oriented, and able to follow commands. Her neck was supple. Ptosis and miosis of the left eye were noted; the neurologic examination was otherwise normal. The hematocrit, hemoglobin level, and blood levels of electrolytes, glucose, and thyrotropin were normal, as were the results of kidney-function and liver-function tests. Other laboratory test results are shown in Table 1.	
Table 1 
Computed tomography (CT) of the head showed no evidence of an acute intracranial process, and there was a finding suggestive of an inferior basal ganglia cyst that appeared unchanged from that seen on imaging that had been performed 5 years earlier. Magnetic resonance imaging (MRI) and magnetic resonance arteriography of the head and neck revealed stable, scattered demyelinating plaques; no active demyelinating lesions were seen, and there was no evidence of venous sinus thrombosis or cavernous sinus thrombosis. The patient received intravenous fluids, ondansetron, diphenhydramine, metoclopramide, magnesium sulfate, and morphine, but the headache persisted. Intravenous hydromorphone, ketorolac, and methylprednisolone were subsequently administered, which led to a moderate reduction in pain. The patient was discharged home and was instructed to take diclofenac and oral methylprednisolone for 5 days.
One day after discharge, and 5 days before admission to this hospital, the headache and nausea recurred, along with intermittent episodes of vomiting. Four days before this admission, lethargy, disorientation, and decreased verbal output developed. The patient was able to follow commands, but verbal responses to questions were limited to ""yes"" and ""no."" She had no fever, chills, chest pain, shortness of breath, cough, dizziness, loss of consciousness, convulsive movements, incontinence, facial droop, or slurred speech. The patient was taken by ambulance to the emergency department of the other hospital.
On examination, the patient was alert but confused. The temperature was 37.3[degrees]C, the pulse 110 beats per minute, the blood pressure 160/110 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 96% while she was breathing ambient air. She was able to follow commands, and the neurologic examination was unchanged from the previous examination. Levels of electrolytes and glucose were normal, as were the results of kidney-function and liver-function tests; a urine toxicology screen was positive for cannabinoids. Other laboratory test results are shown in Table 1. CT of the head was unchanged from the CT performed 3 days earlier, and a chest radiograph was normal. Intravenous ketorolac, famotidine, and pantoprazole were administered, and the patient was admitted to the other hospital.
The next morning, a fever with a temperature of up to 38.0[degrees]C developed. Repeat MRI of the head revealed no notable change from the previous MRI. A lumbar puncture was performed; the opening pressure was 28 cm of water, and 6 ml of clear cerebrospinal fluid (CSF) was removed. The results of the CSF analysis are shown in Table 1. Testing of the CSF for autoantibodies associated with autoimmune and paraneoplastic encephalopathy was performed. Specimens of blood, urine, and CSF were obtained for culture, and the patient received empirical intravenous acyclovir, vancomycin, and meropenem. That evening, nuchal rigidity was noted. During the next 3 days, the patient's mental status waxed and waned but was persistently poor overall, and she had a fever with a temperature of up to 39.0[degrees]C. She was transferred to the neurology service of this hospital for further evaluation.
On the patient's admission to this hospital, her husband reported that her verbal output had increased since admission to the other hospital, such that responses to questions now included words and phrases. The patient had a history of multiple sclerosis, which had been stable for many years with treatment with rituximab. She had seronegative inflammatory polyarthritis with progressive symptoms, despite increased use of immunosuppressive therapies. She also had a history of hypertension, depression, anxiety, and melanoma. An episode of sinusitis had occurred 10 weeks before admission to this hospital and had resolved after the administration of doxycycline. She had undergone an extended carpal tunnel release of the right wrist and radical flexor tenosynovectomy for inflammatory flexor tenosynovitis. Medications before admission included rituximab, hydroxychloroquine (started 18 months before admission), leflunomide (started 11 months before admission), methylprednisolone (started 18 months before admission), butalbital-acetaminophen-caffeine combination tablets, diclofenac, hydrocodone-acetaminophen, inhaled albuterol, duloxetine, bupropion, quetiapine, trazodone, lisinopril, nifedipine, cholecalciferol, and folic acid. She was allergic to penicillin, levofloxacin, cephalosporins, and sulfonamide-containing medications.
The patient was married and had three school-age children; she lived with her family in a suburban community in New England and spent summers on Cape Cod, in Massachusetts. She was receiving disability benefits and spent most of her time indoors. There was no recent history of travel. She had a healthy dog. She had smoked 10 cigarettes daily for 7 years and had quit 22 years before this admission. She drank alcoholic beverages in moderation and reported no use of illicit drugs. Her mother had had coronary artery disease, diabetes, and migraine; her father had had hypertension, diabetes, atrial fibrillation, and multiple sclerosis.
On examination, the temperature was 36.3[degrees]C, the pulse 90 beats per minute, the blood pressure 106/65 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. She was awake, alert, and oriented to her name. The sclerae and conjunctivae were clear, and the pupils were symmetric and reactive, with no afferent pupillary defect. Repetitive blinking and squinting in the left eye were noted, but there was no definite ptosis or facial droop. No oropharyngeal exudates were present, and there was no erythema. Mild resistance to neck flexion was noted. The lungs were clear. There were ulcers on the distal fingers, but no rashes were noted. Muscle tone and strength were normal, as was sensation to light touch. Reflexes were normal, and there was no startle myoclonus; a mild postural tremor was seen. The patient wrote ""magical"" when asked to write her name. She was able to follow simple, but not complex, commands. Laboratory testing revealed a blood sodium level of 133 mmol per liter (reference range, 135 to 145). The levels of other electrolytes, glucose, creatine kinase, and lactic acid were normal, as were the results of kidney-function and liver-function tests. Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2 were negative. Bacterial cultures of the blood, urine, and CSF that were obtained at the other hospital before the initiation of antibiotic agents were negative, as was testing of the CSF for autoantibodies.
Dr. Karen A. Buch: On admission to this hospital, MRI of the head, performed after the administration of intravenous contrast material, revealed subtle leptomeningeal enhancement in the posterior fossa. T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging showed signal hyperintensity in the sulci of the temporal and occipital lobes, as well as signal hyperintensity in the right posterior periatrial region that corresponded with a punctate focus of restricted diffusion (Figure 1).	
Figure 1 
Dr. Baron: Empirical treatment with doxycycline was initiated, and the administration of intravenous acyclovir and meropenem was continued. A repeat lumbar puncture was performed, and the results of the CSF analysis are shown in Table 1. During the subsequent 2 days, the patient's mental status remained poor. An electroencephalogram showed diffuse theta slowing in the background, with no epileptiform activity. The next day, a fever with a temperature of up to 38.6[degrees]C developed, along with loss of all verbal output and an inconsistent ability to follow commands.
Dr. Buch: Follow-up MRI of the head, performed after the administration of intravenous contrast material, revealed the presence of new hydrocephalus, progressive and extensive leptomeningeal enhancement, and abnormal enhancement in the choroid plexus and ependyma of the lateral ventricles. T2-weighted FLAIR imaging showed extensive periventricular signal hyperintensity throughout both cerebral hemispheres, in the dentate nuclei, and surrounding the fourth ventricle, as well as signal hyperintensity in the bilateral basal ganglia, bilateral hippocampi, splenium of the corpus callosum, and periventricular white matter that corresponded to areas of restricted diffusion (Figure 2).	
Figure 2
A diagnostic test result was received
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 45-year-old woman with multiple sclerosis, seronegative inflammatory polyarthritis, and migraine was admitted to this hospital during the winter because of lethargy and decreased verbal output.
The patient had been in her usual state of health until 13 days before this admission, when a severe headache developed. The pain began insidiously, was pounding in quality, and radiated from the occiput to the retro-orbital area and forehead. The onset of pain coincided with visual aura, including blurring of the peripheral vision and oscillating flashes of light. The headache was reminiscent of the patient's previous migraine headaches, the last of which had occurred more than 10 years earlier; symptoms had typically abated with butalbital-acetaminophen-caffeine therapy.
Five days later, and 8 days before this admission, symptoms worsened, and the patient sought care at the emergency department at another hospital. On arrival, she reported photophobia, nausea, and vomiting; she had no history of head injury, and she reported no neck pain, fever, chills, numbness, tingling, weakness, or dizziness. On examination, the temperature was 37.1[degrees]C, the pulse 101 beats per minute, the blood pressure 147/98 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. She appeared uncomfortable and was lying in bed in a dark room with her eyes covered. She was alert, oriented, and able to follow commands. Her neck was supple. Ptosis and miosis of the left eye were noted; the neurologic examination was otherwise normal. The hematocrit, hemoglobin level, and blood levels of electrolytes, glucose, and thyrotropin were normal, as were the results of kidney-function and liver-function tests. Other laboratory test results are shown in Table 1.	
Table 1 
Computed tomography (CT) of the head showed no evidence of an acute intracranial process, and there was a finding suggestive of an inferior basal ganglia cyst that appeared unchanged from that seen on imaging that had been performed 5 years earlier. Magnetic resonance imaging (MRI) and magnetic resonance arteriography of the head and neck revealed stable, scattered demyelinating plaques; no active demyelinating lesions were seen, and there was no evidence of venous sinus thrombosis or cavernous sinus thrombosis. The patient received intravenous fluids, ondansetron, diphenhydramine, metoclopramide, magnesium sulfate, and morphine, but the headache persisted. Intravenous hydromorphone, ketorolac, and methylprednisolone were subsequently administered, which led to a moderate reduction in pain. The patient was discharged home and was instructed to take diclofenac and oral methylprednisolone for 5 days.
One day after discharge, and 5 days before admission to this hospital, the headache and nausea recurred, along with intermittent episodes of vomiting. Four days before this admission, lethargy, disorientation, and decreased verbal output developed. The patient was able to follow commands, but verbal responses to questions were limited to ""yes"" and ""no."" She had no fever, chills, chest pain, shortness of breath, cough, dizziness, loss of consciousness, convulsive movements, incontinence, facial droop, or slurred speech. The patient was taken by ambulance to the emergency department of the other hospital.
On examination, the patient was alert but confused. The temperature was 37.3[degrees]C, the pulse 110 beats per minute, the blood pressure 160/110 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 96% while she was breathing ambient air. She was able to follow commands, and the neurologic examination was unchanged from the previous examination. Levels of electrolytes and glucose were normal, as were the results of kidney-function and liver-function tests; a urine toxicology screen was positive for cannabinoids. Other laboratory test results are shown in Table 1. CT of the head was unchanged from the CT performed 3 days earlier, and a chest radiograph was normal. Intravenous ketorolac, famotidine, and pantoprazole were administered, and the patient was admitted to the other hospital.
The next morning, a fever with a temperature of up to 38.0[degrees]C developed. Repeat MRI of the head revealed no notable change from the previous MRI. A lumbar puncture was performed; the opening pressure was 28 cm of water, and 6 ml of clear cerebrospinal fluid (CSF) was removed. The results of the CSF analysis are shown in Table 1. Testing of the CSF for autoantibodies associated with autoimmune and paraneoplastic encephalopathy was performed. Specimens of blood, urine, and CSF were obtained for culture, and the patient received empirical intravenous acyclovir, vancomycin, and meropenem. That evening, nuchal rigidity was noted. During the next 3 days, the patient's mental status waxed and waned but was persistently poor overall, and she had a fever with a temperature of up to 39.0[degrees]C. She was transferred to the neurology service of this hospital for further evaluation.
On the patient's admission to this hospital, her husband reported that her verbal output had increased since admission to the other hospital, such that responses to questions now included words and phrases. The patient had a history of multiple sclerosis, which had been stable for many years with treatment with rituximab. She had seronegative inflammatory polyarthritis with progressive symptoms, despite increased use of immunosuppressive therapies. She also had a history of hypertension, depression, anxiety, and melanoma. An episode of sinusitis had occurred 10 weeks before admission to this hospital and had resolved after the administration of doxycycline. She had undergone an extended carpal tunnel release of the right wrist and radical flexor tenosynovectomy for inflammatory flexor tenosynovitis. Medications before admission included rituximab, hydroxychloroquine (started 18 months before admission), leflunomide (started 11 months before admission), methylprednisolone (started 18 months before admission), butalbital-acetaminophen-caffeine combination tablets, diclofenac, hydrocodone-acetaminophen, inhaled albuterol, duloxetine, bupropion, quetiapine, trazodone, lisinopril, nifedipine, cholecalciferol, and folic acid. She was allergic to penicillin, levofloxacin, cephalosporins, and sulfonamide-containing medications.
The patient was married and had three school-age children; she lived with her family in a suburban community in New England and spent summers on Cape Cod, in Massachusetts. She was receiving disability benefits and spent most of her time indoors. There was no recent history of travel. She had a healthy dog. She had smoked 10 cigarettes daily for 7 years and had quit 22 years before this admission. She drank alcoholic beverages in moderation and reported no use of illicit drugs. Her mother had had coronary artery disease, diabetes, and migraine; her father had had hypertension, diabetes, atrial fibrillation, and multiple sclerosis.
On examination, the temperature was 36.3[degrees]C, the pulse 90 beats per minute, the blood pressure 106/65 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. She was awake, alert, and oriented to her name. The sclerae and conjunctivae were clear, and the pupils were symmetric and reactive, with no afferent pupillary defect. Repetitive blinking and squinting in the left eye were noted, but there was no definite ptosis or facial droop. No oropharyngeal exudates were present, and there was no erythema. Mild resistance to neck flexion was noted. The lungs were clear. There were ulcers on the distal fingers, but no rashes were noted. Muscle tone and strength were normal, as was sensation to light touch. Reflexes were normal, and there was no startle myoclonus; a mild postural tremor was seen. The patient wrote ""magical"" when asked to write her name. She was able to follow simple, but not complex, commands. Laboratory testing revealed a blood sodium level of 133 mmol per liter (reference range, 135 to 145). The levels of other electrolytes, glucose, creatine kinase, and lactic acid were normal, as were the results of kidney-function and liver-function tests. Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2 were negative. Bacterial cultures of the blood, urine, and CSF that were obtained at the other hospital before the initiation of antibiotic agents were negative, as was testing of the CSF for autoantibodies.
Dr. Karen A. Buch: On admission to this hospital, MRI of the head, performed after the administration of intravenous contrast material, revealed subtle leptomeningeal enhancement in the posterior fossa. T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging showed signal hyperintensity in the sulci of the temporal and occipital lobes, as well as signal hyperintensity in the right posterior periatrial region that corresponded with a punctate focus of restricted diffusion (Figure 1).	
Figure 1 
Dr. Baron: Empirical treatment with doxycycline was initiated, and the administration of intravenous acyclovir and meropenem was continued. A repeat lumbar puncture was performed, and the results of the CSF analysis are shown in Table 1. During the subsequent 2 days, the patient's mental status remained poor. An electroencephalogram showed diffuse theta slowing in the background, with no epileptiform activity. The next day, a fever with a temperature of up to 38.6[degrees]C developed, along with loss of all verbal output and an inconsistent ability to follow commands.
Dr. Buch: Follow-up MRI of the head, performed after the administration of intravenous contrast material, revealed the presence of new hydrocephalus, progressive and extensive leptomeningeal enhancement, and abnormal enhancement in the choroid plexus and ependyma of the lateral ventricles. T2-weighted FLAIR imaging showed extensive periventricular signal hyperintensity throughout both cerebral hemispheres, in the dentate nuclei, and surrounding the fourth ventricle, as well as signal hyperintensity in the bilateral basal ganglia, bilateral hippocampi, splenium of the corpus callosum, and periventricular white matter that corresponded to areas of restricted diffusion (Figure 2).	
Figure 2
A diagnostic test result was received
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Neurologic Lyme Disease. \n\nThe patient's symptoms of severe headache, photophobia, nausea, vomiting, lethargy, disorientation, and decreased verbal output, along with her history of living in New England and spending summers on Cape Cod (areas known for high incidence of Lyme disease), suggest a possible tick-borne illness. The MRI findings of leptomeningeal enhancement and signal hyperintensity in various brain regions are consistent with neurologic involvement. The patient's symptoms did not improve with treatment for migraine or with broad-spectrum antibiotics, but did improve with the initiation of doxycycline, a first-line treatment for Lyme disease. The diagnosis is confirmed by the positive result for Lyme disease on the diagnostic test.""
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        ""content"": ""The patient's symptoms of severe headache, photophobia, nausea, vomiting, and decreased verbal output, along with the MRI findings of leptomeningeal enhancement and periventricular signal hyperintensity, suggest a central nervous system infection. The patient's history of multiple sclerosis and immunosuppressive therapy increases her risk for opportunistic infections. The patient's CSF analysis shows lymphocytic pleocytosis, which is consistent with a viral or atypical bacterial infection. The patient's symptoms did not improve with broad-spectrum antibiotics and antiviral therapy, suggesting an atypical pathogen. The patient's history of spending summers in Cape Cod, an endemic area for ticks, raises the possibility of a tick-borne illness. The patient's CSF was tested for Borrelia burgdorferi, the causative agent of Lyme disease, and the test was positive. Therefore, the patient's symptoms and test results are consistent with neurologic Lyme disease, specifically Lyme meningitis.\n\nDiagnosis: Neurologic Lyme disease, specifically Lyme meningitis.""
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        ""content"": ""This is a 45-year-old woman with a history of multiple sclerosis, seronegative inflammatory polyarthritis, and migraine who presents with severe headache, nausea, vomiting, lethargy, disorientation, and decreased verbal output. The differential diagnosis for this patient includes central nervous system (CNS) infection, CNS vasculitis, CNS lymphoma, and autoimmune encephalitis. The patient's history of multiple sclerosis and seronegative inflammatory polyarthritis suggests a predisposition to autoimmune conditions, making autoimmune encephalitis a possibility. However, the patient's fever, headache, and altered mental status also raise concern for a CNS infection. The patient's CSF analysis shows a lymphocytic pleocytosis, which is more suggestive of a viral infection or autoimmune process than a bacterial infection. The patient's MRI findings of leptomeningeal enhancement and periventricular signal hyperintensity are concerning for an inflammatory or infectious process. The patient's history of immunosuppressive therapy also increases her risk for opportunistic infections. The patient's symptoms did not improve with broad-spectrum antibiotics and antiviral therapy, making an infectious etiology less likely. The patient's CSF analysis did not show oligoclonal bands, which are typically seen in multiple sclerosis, making a multiple sclerosis flare less likely. The patient's symptoms also did not improve with steroids, making CNS vasculitis less likely. The patient's CSF analysis was negative for malignant cells, making CNS lymphoma less likely. The patient's symptoms, CSF findings, and MRI findings are most consistent with autoimmune encephalitis.\n\nDiagnosis: Autoimmune Encephalitis.""
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10.1056/NEJMcpc1900423,Case 30-2019: A 65-Year-Old Woman with Lung Cancer and Chest Pain,"Hemoglobin (g/dl)  10.6   8.9
Hematocrit (%)  33.0   28.0
White-cell count (per mm3
)   12,740   11,710
Platelet count (per mm3
) 135,00 0,000 341,000   304,000
Sodium (mmol/liter)  138   137
Potassium (mmol/liter)  4.6   4.3
Chloride (mmol/liter)  97   102
Carbon dioxide (mmol/liter) 28   22
Urea nitrogen (mg/dl)   15   15
Creatinine (mg/dl) 0.50–1.30 0.61   0.60
Glucose (mg/dl) 74–106 103   109
Troponin T (ng/ml) 0.00–0.01 0.19 <0.03 0.21 0.22
Calcium (mg/dl)   8.1
Albumin (g/dl)   2.5
N-terminal pro–B-type natriuretic 
peptide (pg/ml)
  477
Prothrombin time (sec)   16.6
International normalized ratio   1.4
Partial-thromboplastin time (sec) 22. 5.0 37.9
d-dimer (ng/ml)   2006",Active myocarditis consistent with myocarditis related to immune checkpoint inhibition.,Nonischemic chest pain most likely due to myocarditis associated with the use of an immune checkpoint inhibitor.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 65-year-old woman was transferred to this hospital because of chest pain.
Six months before the current presentation, the patient presented to a hospital affiliated with this hospital with a 4-day history of acute pain in the lower back, left paraspinal muscles, and right flank. The pain worsened with movement and, to a lesser extent, with inspiration. Imaging studies were obtained.
Dr. Mannudeep K. Kalra: A frontal radiograph of the chest (Figure 1A) showed a spiculated nodule in the left lung, with left hilar prominence. Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material according to a pulmonary embolism protocol (Figure 1B), revealed a spiculated nodule (1.7 cm in diameter) in the left upper lobe and left hilar lymphadenopathy. There were bone lesions in the thoracic skeleton, including a lytic lesion (2.3 cm in diameter) at the level of the ninth thoracic vertebra. There was no evidence of pulmonary embolism. Positron-emission tomography and CT (PET-CT) revealed foci of 18F-fluorodeoxyglucose (FDG) avidity in the mass in the left upper lobe, as well as in mediastinal and hilar lymph nodes, the eighth transverse process, the ninth thoracic vertebral body, and the right ninth rib (Figure 1C).	
Figure 1 
A biopsy specimen of the lung mass showed evidence of lung adenocarcinoma with a mutation in KRAS. Magnetic resonance imaging (MRI) of the head and spine did not reveal cerebral metastases but confirmed the presence of a lytic lesion at the level of the eighth and ninth thoracic vertebrae; a compression fracture was also observed.
Dr. Lopes: External-beam radiation therapy was administered during the next 2 weeks, followed by four cycles of carboplatin and pemetrexed that were completed during the next 3 months.
Dr. Kalra: A repeat PET-CT scan obtained 2 weeks after completion of chemotherapy showed that the FDG-avid foci in the right ninth rib and in lymph nodes in the mediastinum, hilum, and right supraclavicular region had increased in size.
Dr. Lopes: Palliative external-beam radiation therapy was administered. Two weeks later, the patient was readmitted to the other hospital with increased back pain. CT of the chest, performed without the administration of intravenous contrast material, revealed atelectasis in the left upper lobe. The patient was treated with external-beam radiation therapy, prednisone, supplemental oxygen, ipratropium in combination with albuterol, and salmeterol in combination with fluticasone, and she was discharged home 2 days later.
Two days after discharge, the patient presented to the other hospital with dyspnea and hypoxemia. CT of the chest, performed after the administration of intravenous contrast material, revealed complete collapse of the left upper lobe due to an obstructing endobronchial lesion. The patient received prednisone, inhaled albuterol, tiotropium, salmeterol in combination with fluticasone, and five treatments of external-beam radiation therapy during a 7-day hospitalization. One week after discharge, a dose of the immune checkpoint inhibitor nivolumab (3 mg per kilogram of body weight) was administered for the treatment of non-small-cell lung cancer (NSCLC) in the outpatient oncology clinic of the other hospital.
Three weeks later, the back pain and dyspnea worsened, and anorexia and a sore throat developed. Two days later, the patient had new pain in the left lateral chest wall. She described the pain as having a stabbing quality that was nonpleuritic, radiated from back to front, and worsened when she lay on her left side. After 2 days of chest pain, she was evaluated at the emergency department of the other hospital. Treatment with sublingual nitroglycerin did not reduce the chest pain. Examination was notable for a heart rate of 121 beats per minute and tenderness in the left precordium near the anterior axillary and midaxillary lines. An electrocardiogram reportedly did not show any ischemic changes. Laboratory test results are shown in Table 1. A radiograph of the chest reportedly showed left hilar opacity, atelectasis in the left upper lobe, and osteopenia. Aspirin was given orally, and morphine, hydromorphone, normal saline, and heparin were administered intravenously. The patient was transferred to the emergency department of this hospital.	
Table 1
A review of systems was notable for anorexia, fatigue, and constipation, but the patient had no fever, chills, dyspnea, cough, diaphoresis, nausea, emesis, diarrhea, or urinary urgency or frequency. The medical history included hypercholesterolemia, hypothyroidism, gastroesophageal reflux disease, gout, anxiety, and glaucoma; she had undergone kyphoplasty for osteoporosis, internal fixation for an ulnar fracture and radiopatellar dislocation, and when she was in her early 40s, ovary-sparing total abdominal hysterectomy for endometriosis. Medications included inhaled salmeterol in combination with fluticasone, tiotropium, morphine sulfate (controlled release), brimonidine, latanoprost, cholecalciferol, senna, docusate, omeprazole, oxycodone, and acetaminophen as needed for pain. Treatment with erythromycin caused stomach upset. She had smoked 1.5 packs of cigarettes per day from 30 years of age until the diagnosis of lung cancer was made, 6 months before the current presentation; she did not drink alcohol or use illicit drugs. She was retired from working as an administrator. She was widowed, had three adult children, and was serving as a caregiver for her mother. Her father had had coronary artery disease, and her mother had lung cancer, osteoporosis for which she had undergone kyphoplasty, and spinal stenosis for which she had undergone laminectomy.
The temperature was 36.2[degrees]C, the heart rate 116 beats per minute, the blood pressure 128/65 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. She appeared cachectic and was uncomfortable with movement. The jugular venous pressure was 5 cm of water. The heart rhythm was tachycardic, but no cardiac murmur or rub was noted. There was tenderness on palpation of the left and right lateral chest wall. Diminished breath sounds were noted on the left side, with crackles at the left apex. A faint erythematous rash was present at the site of radiation therapy on the left upper back. The patient had no swelling or palpable cords in the legs. The remainder of the examination was normal.
An electrocardiogram (Figure 2) showed sinus tachycardia, a rightward axis, and minor nonspecific ST-segment and T-wave changes. Telemetry revealed intermittent premature ventricular contractions. Laboratory testing revealed normal levels of magnesium, phosphorus, aspartate aminotransferase, alanine aminotransferase, total and direct bilirubin, alkaline phosphatase, lipase, lactic acid, and thyrotropin; other laboratory test results are shown in Table 1. Blood samples were obtained for culture.	
Figure 2 
Dr. Kalra: A frontal radiograph of the chest (Figure 3A) showed an elevated left hilum with adjacent opacity, findings that were consistent with a collapsed left upper lobe. Dual-energy CT of the chest (Figure 3B), performed after the administration of intravenous contrast material according to a pulmonary embolism protocol, revealed a low-attenuation lesion (measuring 2 cm in diameter) at the left hilum that was consistent with the patient's known lung cancer, but there was no evidence of pulmonary embolism. The lesion caused complete occlusion of the bronchus of the left upper lobe at its origin, with obstructive collapse of the left upper lobe. In addition, patchy consolidation was noted in an adjacent area of the left lower lobe. There were multiple lytic lesions in the thoracic skeleton, with the largest lesions seen in the eighth thoracic vertebra and the ninth right rib. The imaging also revealed multiple sites of previous vertebroplasty in the lower thoracic spine.	
Figure 3 
Dr. Lopes: Atorvastatin, levofloxacin, metoprolol, and intravenous hydromorphone and morphine were administered, and the patient was admitted to the cardiology service. A transthoracic echocardiogram showed a left ventricular ejection fraction of 57%; there was subtle hypokinesis in the mid-inferior, basal inferior, and basal inferoseptal walls, mild-to-moderate tricuspid regurgitation, and no evidence of pericardial effusion, and the size and function of the right ventricle were normal.
Diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 65-year-old woman was transferred to this hospital because of chest pain.
Six months before the current presentation, the patient presented to a hospital affiliated with this hospital with a 4-day history of acute pain in the lower back, left paraspinal muscles, and right flank. The pain worsened with movement and, to a lesser extent, with inspiration. Imaging studies were obtained.
Dr. Mannudeep K. Kalra: A frontal radiograph of the chest (Figure 1A) showed a spiculated nodule in the left lung, with left hilar prominence. Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material according to a pulmonary embolism protocol (Figure 1B), revealed a spiculated nodule (1.7 cm in diameter) in the left upper lobe and left hilar lymphadenopathy. There were bone lesions in the thoracic skeleton, including a lytic lesion (2.3 cm in diameter) at the level of the ninth thoracic vertebra. There was no evidence of pulmonary embolism. Positron-emission tomography and CT (PET-CT) revealed foci of 18F-fluorodeoxyglucose (FDG) avidity in the mass in the left upper lobe, as well as in mediastinal and hilar lymph nodes, the eighth transverse process, the ninth thoracic vertebral body, and the right ninth rib (Figure 1C).	
Figure 1 
A biopsy specimen of the lung mass showed evidence of lung adenocarcinoma with a mutation in KRAS. Magnetic resonance imaging (MRI) of the head and spine did not reveal cerebral metastases but confirmed the presence of a lytic lesion at the level of the eighth and ninth thoracic vertebrae; a compression fracture was also observed.
Dr. Lopes: External-beam radiation therapy was administered during the next 2 weeks, followed by four cycles of carboplatin and pemetrexed that were completed during the next 3 months.
Dr. Kalra: A repeat PET-CT scan obtained 2 weeks after completion of chemotherapy showed that the FDG-avid foci in the right ninth rib and in lymph nodes in the mediastinum, hilum, and right supraclavicular region had increased in size.
Dr. Lopes: Palliative external-beam radiation therapy was administered. Two weeks later, the patient was readmitted to the other hospital with increased back pain. CT of the chest, performed without the administration of intravenous contrast material, revealed atelectasis in the left upper lobe. The patient was treated with external-beam radiation therapy, prednisone, supplemental oxygen, ipratropium in combination with albuterol, and salmeterol in combination with fluticasone, and she was discharged home 2 days later.
Two days after discharge, the patient presented to the other hospital with dyspnea and hypoxemia. CT of the chest, performed after the administration of intravenous contrast material, revealed complete collapse of the left upper lobe due to an obstructing endobronchial lesion. The patient received prednisone, inhaled albuterol, tiotropium, salmeterol in combination with fluticasone, and five treatments of external-beam radiation therapy during a 7-day hospitalization. One week after discharge, a dose of the immune checkpoint inhibitor nivolumab (3 mg per kilogram of body weight) was administered for the treatment of non-small-cell lung cancer (NSCLC) in the outpatient oncology clinic of the other hospital.
Three weeks later, the back pain and dyspnea worsened, and anorexia and a sore throat developed. Two days later, the patient had new pain in the left lateral chest wall. She described the pain as having a stabbing quality that was nonpleuritic, radiated from back to front, and worsened when she lay on her left side. After 2 days of chest pain, she was evaluated at the emergency department of the other hospital. Treatment with sublingual nitroglycerin did not reduce the chest pain. Examination was notable for a heart rate of 121 beats per minute and tenderness in the left precordium near the anterior axillary and midaxillary lines. An electrocardiogram reportedly did not show any ischemic changes. Laboratory test results are shown in Table 1. A radiograph of the chest reportedly showed left hilar opacity, atelectasis in the left upper lobe, and osteopenia. Aspirin was given orally, and morphine, hydromorphone, normal saline, and heparin were administered intravenously. The patient was transferred to the emergency department of this hospital.	
Table 1
A review of systems was notable for anorexia, fatigue, and constipation, but the patient had no fever, chills, dyspnea, cough, diaphoresis, nausea, emesis, diarrhea, or urinary urgency or frequency. The medical history included hypercholesterolemia, hypothyroidism, gastroesophageal reflux disease, gout, anxiety, and glaucoma; she had undergone kyphoplasty for osteoporosis, internal fixation for an ulnar fracture and radiopatellar dislocation, and when she was in her early 40s, ovary-sparing total abdominal hysterectomy for endometriosis. Medications included inhaled salmeterol in combination with fluticasone, tiotropium, morphine sulfate (controlled release), brimonidine, latanoprost, cholecalciferol, senna, docusate, omeprazole, oxycodone, and acetaminophen as needed for pain. Treatment with erythromycin caused stomach upset. She had smoked 1.5 packs of cigarettes per day from 30 years of age until the diagnosis of lung cancer was made, 6 months before the current presentation; she did not drink alcohol or use illicit drugs. She was retired from working as an administrator. She was widowed, had three adult children, and was serving as a caregiver for her mother. Her father had had coronary artery disease, and her mother had lung cancer, osteoporosis for which she had undergone kyphoplasty, and spinal stenosis for which she had undergone laminectomy.
The temperature was 36.2[degrees]C, the heart rate 116 beats per minute, the blood pressure 128/65 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. She appeared cachectic and was uncomfortable with movement. The jugular venous pressure was 5 cm of water. The heart rhythm was tachycardic, but no cardiac murmur or rub was noted. There was tenderness on palpation of the left and right lateral chest wall. Diminished breath sounds were noted on the left side, with crackles at the left apex. A faint erythematous rash was present at the site of radiation therapy on the left upper back. The patient had no swelling or palpable cords in the legs. The remainder of the examination was normal.
An electrocardiogram (Figure 2) showed sinus tachycardia, a rightward axis, and minor nonspecific ST-segment and T-wave changes. Telemetry revealed intermittent premature ventricular contractions. Laboratory testing revealed normal levels of magnesium, phosphorus, aspartate aminotransferase, alanine aminotransferase, total and direct bilirubin, alkaline phosphatase, lipase, lactic acid, and thyrotropin; other laboratory test results are shown in Table 1. Blood samples were obtained for culture.	
Figure 2 
Dr. Kalra: A frontal radiograph of the chest (Figure 3A) showed an elevated left hilum with adjacent opacity, findings that were consistent with a collapsed left upper lobe. Dual-energy CT of the chest (Figure 3B), performed after the administration of intravenous contrast material according to a pulmonary embolism protocol, revealed a low-attenuation lesion (measuring 2 cm in diameter) at the left hilum that was consistent with the patient's known lung cancer, but there was no evidence of pulmonary embolism. The lesion caused complete occlusion of the bronchus of the left upper lobe at its origin, with obstructive collapse of the left upper lobe. In addition, patchy consolidation was noted in an adjacent area of the left lower lobe. There were multiple lytic lesions in the thoracic skeleton, with the largest lesions seen in the eighth thoracic vertebra and the ninth right rib. The imaging also revealed multiple sites of previous vertebroplasty in the lower thoracic spine.	
Figure 3 
Dr. Lopes: Atorvastatin, levofloxacin, metoprolol, and intravenous hydromorphone and morphine were administered, and the patient was admitted to the cardiology service. A transthoracic echocardiogram showed a left ventricular ejection fraction of 57%; there was subtle hypokinesis in the mid-inferior, basal inferior, and basal inferoseptal walls, mild-to-moderate tricuspid regurgitation, and no evidence of pericardial effusion, and the size and function of the right ventricle were normal.
Diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient initially presented with back pain and was found to have a spiculated nodule in the left lung, left hilar lymphadenopathy, and bone lesions in the thoracic skeleton. A biopsy of the lung mass showed lung adenocarcinoma with a mutation in KRAS. Despite treatment, the patient's condition worsened, with increased back pain, dyspnea, anorexia, and a sore throat. She also developed new pain in the left lateral chest wall. The patient's medical history, symptoms, and test results all point to a diagnosis of metastatic non-small-cell lung cancer (NSCLC).""
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        ""content"": ""The patient initially presented with back pain and was found to have a spiculated nodule in the left lung, left hilar lymphadenopathy, and bone lesions in the thoracic skeleton. A biopsy of the lung mass showed lung adenocarcinoma with a mutation in KRAS. Despite treatment, the patient's condition worsened, with increased back pain, dyspnea, anorexia, and a sore throat. She also developed new pain in the left lateral chest wall. The patient's medical history, symptoms, and test results all point to a diagnosis of metastatic non-small-cell lung cancer (NSCLC). \n\nDiagnosis: Metastatic non-small-cell lung cancer (NSCLC)""
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        ""content"": ""The patient is a 65-year-old woman with a history of lung adenocarcinoma who presents with chest pain. The differential diagnosis for this patient includes myocardial infarction, pulmonary embolism, pneumonia, and cancer-related complications such as metastasis or pleural effusion. The patient's EKG does not show any ischemic changes, making myocardial infarction less likely. CT of the chest does not show any evidence of pulmonary embolism. The patient does not have fever or cough, making pneumonia less likely. The patient's known lung adenocarcinoma, along with the presence of multiple lytic lesions in the thoracic skeleton, suggests that the chest pain could be due to cancer-related complications. The patient's chest pain could be due to metastasis to the bones or pleura. The patient's history of radiation therapy could also contribute to the chest pain. The patient's chest pain could also be due to the obstructive collapse of the left upper lobe caused by the lung cancer. \n\nDiagnosis: Chest pain due to complications of lung adenocarcinoma.""
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10.1056/NEJMcpc1904049,Case 29-2019: A 14-Month-Old Boy with Vomiting,,Congenital esophageal stenosis with fibromuscular thickening of the esophagus.,Congenital esophageal stenosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 14-month-old boy was evaluated in the pediatric gastroenterology clinic of this hospital because of vomiting.
The patient was born at another hospital to a 35-year-old mother by cesarean section because of arrest of the second stage of labor after an uncomplicated gestation of 39 weeks 6 days. At delivery, meconium was present. The 1-minute and 5-minute Apgar scores were both 9, and the birth weight was 2.9 kg (23rd percentile) (Figure 1). Breast-feeding was initiated. The results of newborn blood-spot screening tests (a panel of tests for multiple congenital diseases, primarily inborn errors of metabolism) and screening tests for hearing ability and critical congenital heart disease were normal, and the patient was discharged home on the fourth day of life.	
Figure 1 
At a routine pediatric examination when the patient was 14 days of age, the patient's mother reported that she had been breast-feeding him for 20 minutes every 2 to 3 hours and that he was having yellow, seedy stools after each feeding. The weight was 2.7 kg. The patient's mother was advised to begin pumping breast milk and fortifying it with a cow's milk-based infant formula to achieve a caloric content of 0.74 kcal per milliliter. Eight days later, the weight was 2.8 kg, and fortification to 0.81 kcal per milliliter was recommended.
At 26 days of age, the patient vomited a small amount of clotted blood, and his parents took him to the emergency department at another hospital. They reported that the baby had begun having frequent nonprojectile, nonbloody, nonbilious ""spit ups"" after the initiation of formula-fortified expressed breast milk. The physical examination was normal. A test of the stool was positive for occult blood. The patient was monitored overnight; he had no recurrent hematemesis and was discharged home the next day. At a follow-up visit with the pediatrician 9 days later, the weight was 2.8 kg, and the patient was referred to a pediatric gastroenterologist at this hospital.
The patient was seen in the pediatric gastroenterology clinic when he was 37 days of age. His mother reported that he had been consuming 60 ml of formula-fortified expressed breast milk every 2.5 hours. He had continued to have occasional small-volume emesis after feedings, but no additional episodes of hematemesis had occurred. Bowel movements had occurred after each feeding, and the stools were brown-green without visible blood or mucus. On examination, the infant was active and had a strong cry. The weight was 2.8 kg (<1st percentile), and the height was 55 cm (31st percentile). The abdomen was soft, nontender, and nondistended, with normal bowel sounds. Rectal examination revealed guaiac-positive, brown stool; the remainder of the examination was normal. A clinical diagnosis of allergy to cow's milk protein was made, and a hypoallergenic formula with a caloric content of 0.81 kcal per milliliter was recommended.
At a follow-up visit at the pediatric gastroenterology clinic 3 weeks later, when the patient was 58 days of age, the patient's mother reported that the frequency of emesis had decreased and that stools had occasionally contained mucus but no blood. She reported that the baby had had nasal congestion and that she could hear a ""gurgling"" sound during bottle-feeding. On examination, the weight was 3.6 kg. Rectal examination revealed soft, guaiac-positive stool with mucus; the remainder of the examination was normal. Transition to an amino acid-based formula (also known as an elemental formula) with a caloric content of 0.81 kcal per milliliter was recommended.
Eight weeks later, when the patient was 16 weeks of age, he was brought back to the pediatric gastroenterology clinic because, during the preceding week, he had had several episodes of small-volume emesis with the vomitus containing dark-brown material that his parents thought resembled blood. The weight was 4.6 kg; the remainder of the physical examination was normal. Omeprazole was prescribed for the treatment of possible gastroesophageal reflux disease (GERD), and preparation of the elemental formula to a caloric content of 0.88 kcal per milliliter was recommended.
At a follow-up visit at the pediatric gastroenterology clinic 2 months later, when the patient was 6 months of age, his parents reported that he had seemed uncomfortable during feedings and had appeared to be increasingly hungry. The frequency of emesis had increased; he had been vomiting formula after approximately 75% of feedings. The weight was 6.2 kg; the remainder of the physical examination was normal. The dose of omeprazole was adjusted for the patient's current weight, and the introduction of age-appropriate, dairy-free solid foods into his diet was recommended.
One month later, when the patient was 7 months of age, his parents reported that he had continued to gain weight and that he had had no complications when they introduced soft foods, including cooked carrots, avocados, and bananas, into his diet. There had been no visible blood in the vomitus, and stools had appeared normal in color. Cow's milk protein was slowly reintroduced into his diet; he had no negative consequences, and treatment with omeprazole was discontinued.
Six months later, when the patient was 13 months of age, his mother called the pediatric gastroenterologist and reported that the frequency of vomiting had increased. Omeprazole was prescribed. At a follow-up visit in the pediatric gastroenterology clinic 5 weeks later, the patient's mother reported that she had stopped administering omeprazole to the patient after 2 weeks because it seemed not to have any effect. Immediately after eating each meal, the patient had appeared uncomfortable, retched, and then vomited; at times, he had inserted his fingers into his mouth and appeared to induce vomiting. The vomitus often contained nearly everything the patient had just eaten, typically resembling his undigested food, without blood or bile. Emesis had occurred usually after consumption of pureed and solid foods and less frequently after consumption of milk. Shortly after vomiting, the patient usually requested more milk or food. Review of recent dietary records showed that the patient ate nearly every 30 minutes throughout the day, with typical meals including whole milk, a spoonful of oatmeal or banana, and rice puffs. Bowel movements occurred regularly twice per day; stools remained soft and did not contain visible blood or mucus.
The patient had met normal developmental milestones, and immunizations were up to date. At the 1-year health supervision visit with his pediatrician, the blood levels of hemoglobin and lead were normal. The patient had been receiving a vitamin D supplement and had no known medication allergies. He lived with his parents in an urban area of New England. His mother had anemia, and his father and younger sister were healthy. A maternal aunt had hyperthyroidism, his maternal grandmother had pancreatitis, and his maternal grandfather had hypertension. On examination, the patient was active and appeared well. The weight was 6.9 kg. The abdomen was soft, with normal bowel sounds and without distention or tenderness. Rectal examination revealed guaiac-negative stool. The remainder of the examination was normal. The complete blood count and differential count were normal, as was the blood level of IgE antibodies to cow's milk.
Diagnostic studies were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 14-month-old boy was evaluated in the pediatric gastroenterology clinic of this hospital because of vomiting.
The patient was born at another hospital to a 35-year-old mother by cesarean section because of arrest of the second stage of labor after an uncomplicated gestation of 39 weeks 6 days. At delivery, meconium was present. The 1-minute and 5-minute Apgar scores were both 9, and the birth weight was 2.9 kg (23rd percentile) (Figure 1). Breast-feeding was initiated. The results of newborn blood-spot screening tests (a panel of tests for multiple congenital diseases, primarily inborn errors of metabolism) and screening tests for hearing ability and critical congenital heart disease were normal, and the patient was discharged home on the fourth day of life.	
Figure 1 
At a routine pediatric examination when the patient was 14 days of age, the patient's mother reported that she had been breast-feeding him for 20 minutes every 2 to 3 hours and that he was having yellow, seedy stools after each feeding. The weight was 2.7 kg. The patient's mother was advised to begin pumping breast milk and fortifying it with a cow's milk-based infant formula to achieve a caloric content of 0.74 kcal per milliliter. Eight days later, the weight was 2.8 kg, and fortification to 0.81 kcal per milliliter was recommended.
At 26 days of age, the patient vomited a small amount of clotted blood, and his parents took him to the emergency department at another hospital. They reported that the baby had begun having frequent nonprojectile, nonbloody, nonbilious ""spit ups"" after the initiation of formula-fortified expressed breast milk. The physical examination was normal. A test of the stool was positive for occult blood. The patient was monitored overnight; he had no recurrent hematemesis and was discharged home the next day. At a follow-up visit with the pediatrician 9 days later, the weight was 2.8 kg, and the patient was referred to a pediatric gastroenterologist at this hospital.
The patient was seen in the pediatric gastroenterology clinic when he was 37 days of age. His mother reported that he had been consuming 60 ml of formula-fortified expressed breast milk every 2.5 hours. He had continued to have occasional small-volume emesis after feedings, but no additional episodes of hematemesis had occurred. Bowel movements had occurred after each feeding, and the stools were brown-green without visible blood or mucus. On examination, the infant was active and had a strong cry. The weight was 2.8 kg (<1st percentile), and the height was 55 cm (31st percentile). The abdomen was soft, nontender, and nondistended, with normal bowel sounds. Rectal examination revealed guaiac-positive, brown stool; the remainder of the examination was normal. A clinical diagnosis of allergy to cow's milk protein was made, and a hypoallergenic formula with a caloric content of 0.81 kcal per milliliter was recommended.
At a follow-up visit at the pediatric gastroenterology clinic 3 weeks later, when the patient was 58 days of age, the patient's mother reported that the frequency of emesis had decreased and that stools had occasionally contained mucus but no blood. She reported that the baby had had nasal congestion and that she could hear a ""gurgling"" sound during bottle-feeding. On examination, the weight was 3.6 kg. Rectal examination revealed soft, guaiac-positive stool with mucus; the remainder of the examination was normal. Transition to an amino acid-based formula (also known as an elemental formula) with a caloric content of 0.81 kcal per milliliter was recommended.
Eight weeks later, when the patient was 16 weeks of age, he was brought back to the pediatric gastroenterology clinic because, during the preceding week, he had had several episodes of small-volume emesis with the vomitus containing dark-brown material that his parents thought resembled blood. The weight was 4.6 kg; the remainder of the physical examination was normal. Omeprazole was prescribed for the treatment of possible gastroesophageal reflux disease (GERD), and preparation of the elemental formula to a caloric content of 0.88 kcal per milliliter was recommended.
At a follow-up visit at the pediatric gastroenterology clinic 2 months later, when the patient was 6 months of age, his parents reported that he had seemed uncomfortable during feedings and had appeared to be increasingly hungry. The frequency of emesis had increased; he had been vomiting formula after approximately 75% of feedings. The weight was 6.2 kg; the remainder of the physical examination was normal. The dose of omeprazole was adjusted for the patient's current weight, and the introduction of age-appropriate, dairy-free solid foods into his diet was recommended.
One month later, when the patient was 7 months of age, his parents reported that he had continued to gain weight and that he had had no complications when they introduced soft foods, including cooked carrots, avocados, and bananas, into his diet. There had been no visible blood in the vomitus, and stools had appeared normal in color. Cow's milk protein was slowly reintroduced into his diet; he had no negative consequences, and treatment with omeprazole was discontinued.
Six months later, when the patient was 13 months of age, his mother called the pediatric gastroenterologist and reported that the frequency of vomiting had increased. Omeprazole was prescribed. At a follow-up visit in the pediatric gastroenterology clinic 5 weeks later, the patient's mother reported that she had stopped administering omeprazole to the patient after 2 weeks because it seemed not to have any effect. Immediately after eating each meal, the patient had appeared uncomfortable, retched, and then vomited; at times, he had inserted his fingers into his mouth and appeared to induce vomiting. The vomitus often contained nearly everything the patient had just eaten, typically resembling his undigested food, without blood or bile. Emesis had occurred usually after consumption of pureed and solid foods and less frequently after consumption of milk. Shortly after vomiting, the patient usually requested more milk or food. Review of recent dietary records showed that the patient ate nearly every 30 minutes throughout the day, with typical meals including whole milk, a spoonful of oatmeal or banana, and rice puffs. Bowel movements occurred regularly twice per day; stools remained soft and did not contain visible blood or mucus.
The patient had met normal developmental milestones, and immunizations were up to date. At the 1-year health supervision visit with his pediatrician, the blood levels of hemoglobin and lead were normal. The patient had been receiving a vitamin D supplement and had no known medication allergies. He lived with his parents in an urban area of New England. His mother had anemia, and his father and younger sister were healthy. A maternal aunt had hyperthyroidism, his maternal grandmother had pancreatitis, and his maternal grandfather had hypertension. On examination, the patient was active and appeared well. The weight was 6.9 kg. The abdomen was soft, with normal bowel sounds and without distention or tenderness. Rectal examination revealed guaiac-negative stool. The remainder of the examination was normal. The complete blood count and differential count were normal, as was the blood level of IgE antibodies to cow's milk.
Diagnostic studies were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms include frequent vomiting, often immediately after eating, and the vomitus often contains undigested food. The patient also appears to be hungry shortly after vomiting. These symptoms, along with the fact that the patient's weight is below the 1st percentile, suggest a problem with food moving through the digestive system. The patient's symptoms do not improve with treatment for gastroesophageal reflux disease or allergy to cow's milk protein, which suggests that these are not the underlying issues. The patient's symptoms are consistent with a diagnosis of rumination syndrome, a functional gastrointestinal disorder characterized by the effortless regurgitation of most meals following consumption, due to the voluntary contraction of abdominal muscles.\n\nDiagnosis: Rumination syndrome.""
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        ""content"": ""The patient is a 14-month-old boy with a history of vomiting, particularly after meals. The differential diagnosis includes gastroesophageal reflux disease (GERD), food allergies, pyloric stenosis, and rumination syndrome. GERD is less likely because the patient's symptoms did not improve with omeprazole treatment. Food allergies are also less likely because the patient's IgE antibodies to cow's milk were normal and his symptoms did not improve with hypoallergenic or elemental formulas. Pyloric stenosis is less likely because the patient's vomiting is not consistently projectile and the condition typically presents earlier in infancy. Rumination syndrome is a behavioral disorder characterized by the voluntary or involuntary regurgitation and rechewing of food, which is then either spit out or reswallowed. This condition is more likely because the patient's vomiting often occurs immediately after meals and contains undigested food, and the patient often requests more food after vomiting. \n\nDiagnosis: Rumination syndrome.""
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10.1056/NEJMcpc1904041,Case 28-2019: A 22-Year-Old Woman with Dyspnea and Chest Pain,,"Interstitial lung disease associated with FLNA
mutation",Mutation in the gene encoding filamin A (FLNA).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 22-year-old woman was seen in the pediatric pulmonary clinic of this hospital because of chest pain, cough, and dyspnea on exertion.
The patient had been well until she was 2 months of age, when an episode of bronchiolitis occurred. After this episode, repeated respiratory illnesses characterized by wheezing and cyanosis developed, and she was hospitalized frequently. The patient was subsequently evaluated by a pediatric pulmonologist at this hospital. Examination revealed decreased breath sounds at the apex of the right lung, and chest radiography revealed findings suggestive of congenital lobar emphysema of the right upper lobe. A blood test for alpha1-antitrypsin deficiency was negative. Transthoracic echocardiography revealed right ventricular dilatation and hypertrophy, mild pulmonary arterial hypertension, and a small patent ductus arteriosus. When the patient was 24 months of age, a right upper lobectomy, coil embolization for the patent ductus arteriosus, and a biopsy of the right middle lobe were performed.
Dr. Mari Mino-Kenudson: Histopathological examination of lung specimens revealed lobar emphysema of the right upper and middle lobes that was characterized by the presence of fewer alveoli than the number typically seen in normal lung tissue and hyperinflation of the existing alveoli (Figure 1A). The number of bronchioles in the peripheral emphysematous areas was disproportionately low relative to the number of pulmonary vessels, and the central bronchi had mucus plugs that may have obliterated the bronchial lumens (Figure 1B). In the hilum, the central bronchi had mucus plugs that resulted in partial obstruction of the bronchial lumens, but the amount and contour of the bronchial cartilage were normal (Figure 1C). No diagnostic findings were consistent with pulmonary hypertension. There are two possible causes of lobar emphysema in this case: obstruction (either intrinsic or extrinsic) of the developing airway, and overinflation of the lung as a result of constrictive bronchiolitis that was possibly due to infection. Intrinsic obstruction is often caused by defects in the bronchial wall, such as a deficiency of bronchial cartilage or intraluminal obstruction by meconium, mucus plugs, or other substances. In this case, the bronchial cartilage was normal. Mucus plugs were observed at the time of lung resection, but they only partially obstructed the central airways. In addition, there was no evidence of constrictive bronchiolitis, although there were fewer bronchioles than normal in the area of the peripheral lung that was involved by lobar emphysema.	
Figure 1 
Dr. Bartley: The patient and her family subsequently moved from the United States to another country, and she received medical care at another hospital. When she was 6 years of age, a spontaneous pneumothorax occurred, and evaluation included genetic testing for Marfan's syndrome, which was reportedly negative. During the next 16 years, while the patient was still living in another country, dyspnea on exertion and decreased exercise tolerance slowly developed, becoming more marked in the 12 months before this presentation.
Approximately 6 weeks before this presentation, intermittent chest pain developed. The pain was sharp, could be reproduced with palpation of the affected area, and was not relieved with the administration of ibuprofen. Episodes occurred both at rest and with exertion; no precipitating or exacerbating factors were identified. The patient was seen in the emergency department of a local hospital, where an electrocardiogram was reportedly normal and a radiograph of the chest showed no pneumothorax. The patient was discharged home, and the chest pain continued to occur every few days until presentation.
On presentation to the pediatric pulmonary clinic of this hospital, the patient reported that her exercise capacity had declined during the past month and that she had become unable to climb a flight of stairs without having severe breathlessness. She also reported a 1-week history of productive cough; the sputum had initially been clear but then had become dark yellow and, on the day before this presentation, blood-tinged. The patient also had diarrhea but had no fever, chills, weight loss, vomiting, or abdominal pain. She had been born after a full-term gestation and had been delivered by cesarean section because of breech presentation; the birth weight was 3175 g. She had a history of depression. Medications included sertraline and inhaled albuterol as needed. She had no known allergies. The patient was fluent in English and Spanish and was an undergraduate student at a European university; she lived on campus during the academic year and spent the rest of the year at her parents' home in the United States. She did not drink alcohol, smoke tobacco, or use illicit drugs. Her younger brother had a seizure disorder and developmental delays; her mother had mild joint hypermobility, and her father was healthy.
On examination, the temperature was 37.1[degrees]C, the pulse 82 beats per minute, the blood pressure 116/72 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 92% while the patient was breathing ambient air at rest. The height was 169 cm, the weight 47.7 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 16.7. A blue hue was noted in the perioral region; no clubbing of the fingers and toes was seen. There was no use of accessory muscles of ventilation; auscultation revealed bronchial breath sounds in the right upper lung fields and diffuse, faint rhonchi during the expiratory phase. Her heart sounds were regular, and no murmur was noted. Hypermobility was present in the joints of the hands and arms. The remainder of the examination was normal.
Pulmonary-function testing was performed. The forced expiratory volume in 1 second (FEV1) was 23% of the predicted value, the forced vital capacity (FVC) was 45% of the predicted value, and the ratio of FEV1 to FVC was 44%. The total lung capacity was 108% of the predicted value, and the ratio of residual volume to total lung capacity was 65%. The diffusing capacity of the lung for carbon monoxide was 26% of the predicted value.
Dr. Brent P. Little: Contrast-enhanced computed tomography (CT) of the chest revealed hyperinflation of the lungs with severe confluent emphysema and multiple apical bullae (Figure 2A, 2B, and 2C); although diffuse thickening of the bronchial wall and areas of parenchymal air trapping were present, bronchiectasis was notably absent. Normal postsurgical findings included a stump from right upper lobectomy and coil from embolization of a patent ductus arteriosus. The main pulmonary artery was enlarged, measuring 3.8 cm in diameter (Figure 2D).	
Figure 2 
Dr. Mark E. Lindsay: Transthoracic echocardiography revealed dilatation of the right atrium, right ventricle, and inferior vena cava; systolic and diastolic flattening of the interventricular septum (see Video 1, available with the full text of this article at
NEJM.org
); and an estimated right ventricular systolic pressure of 65 mm Hg. The aortic root was not enlarged relative to the patient's body size, and the aortic valve was tricuspid. However, the aortic valve was abnormally thickened and was prolapsed, and there was moderate aortic regurgitation, which had not been present on echocardiograms obtained during infancy. Findings suggestive of constrictive pericarditis, including a septal bounce and respiratory variation across the mitral valve, were also seen.
Dr. Bartley: Empirical prednisone and amoxicillin-clavulanic acid were prescribed, and a diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 22-year-old woman was seen in the pediatric pulmonary clinic of this hospital because of chest pain, cough, and dyspnea on exertion.
The patient had been well until she was 2 months of age, when an episode of bronchiolitis occurred. After this episode, repeated respiratory illnesses characterized by wheezing and cyanosis developed, and she was hospitalized frequently. The patient was subsequently evaluated by a pediatric pulmonologist at this hospital. Examination revealed decreased breath sounds at the apex of the right lung, and chest radiography revealed findings suggestive of congenital lobar emphysema of the right upper lobe. A blood test for alpha1-antitrypsin deficiency was negative. Transthoracic echocardiography revealed right ventricular dilatation and hypertrophy, mild pulmonary arterial hypertension, and a small patent ductus arteriosus. When the patient was 24 months of age, a right upper lobectomy, coil embolization for the patent ductus arteriosus, and a biopsy of the right middle lobe were performed.
Dr. Mari Mino-Kenudson: Histopathological examination of lung specimens revealed lobar emphysema of the right upper and middle lobes that was characterized by the presence of fewer alveoli than the number typically seen in normal lung tissue and hyperinflation of the existing alveoli (Figure 1A). The number of bronchioles in the peripheral emphysematous areas was disproportionately low relative to the number of pulmonary vessels, and the central bronchi had mucus plugs that may have obliterated the bronchial lumens (Figure 1B). In the hilum, the central bronchi had mucus plugs that resulted in partial obstruction of the bronchial lumens, but the amount and contour of the bronchial cartilage were normal (Figure 1C). No diagnostic findings were consistent with pulmonary hypertension. There are two possible causes of lobar emphysema in this case: obstruction (either intrinsic or extrinsic) of the developing airway, and overinflation of the lung as a result of constrictive bronchiolitis that was possibly due to infection. Intrinsic obstruction is often caused by defects in the bronchial wall, such as a deficiency of bronchial cartilage or intraluminal obstruction by meconium, mucus plugs, or other substances. In this case, the bronchial cartilage was normal. Mucus plugs were observed at the time of lung resection, but they only partially obstructed the central airways. In addition, there was no evidence of constrictive bronchiolitis, although there were fewer bronchioles than normal in the area of the peripheral lung that was involved by lobar emphysema.	
Figure 1 
Dr. Bartley: The patient and her family subsequently moved from the United States to another country, and she received medical care at another hospital. When she was 6 years of age, a spontaneous pneumothorax occurred, and evaluation included genetic testing for Marfan's syndrome, which was reportedly negative. During the next 16 years, while the patient was still living in another country, dyspnea on exertion and decreased exercise tolerance slowly developed, becoming more marked in the 12 months before this presentation.
Approximately 6 weeks before this presentation, intermittent chest pain developed. The pain was sharp, could be reproduced with palpation of the affected area, and was not relieved with the administration of ibuprofen. Episodes occurred both at rest and with exertion; no precipitating or exacerbating factors were identified. The patient was seen in the emergency department of a local hospital, where an electrocardiogram was reportedly normal and a radiograph of the chest showed no pneumothorax. The patient was discharged home, and the chest pain continued to occur every few days until presentation.
On presentation to the pediatric pulmonary clinic of this hospital, the patient reported that her exercise capacity had declined during the past month and that she had become unable to climb a flight of stairs without having severe breathlessness. She also reported a 1-week history of productive cough; the sputum had initially been clear but then had become dark yellow and, on the day before this presentation, blood-tinged. The patient also had diarrhea but had no fever, chills, weight loss, vomiting, or abdominal pain. She had been born after a full-term gestation and had been delivered by cesarean section because of breech presentation; the birth weight was 3175 g. She had a history of depression. Medications included sertraline and inhaled albuterol as needed. She had no known allergies. The patient was fluent in English and Spanish and was an undergraduate student at a European university; she lived on campus during the academic year and spent the rest of the year at her parents' home in the United States. She did not drink alcohol, smoke tobacco, or use illicit drugs. Her younger brother had a seizure disorder and developmental delays; her mother had mild joint hypermobility, and her father was healthy.
On examination, the temperature was 37.1[degrees]C, the pulse 82 beats per minute, the blood pressure 116/72 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 92% while the patient was breathing ambient air at rest. The height was 169 cm, the weight 47.7 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 16.7. A blue hue was noted in the perioral region; no clubbing of the fingers and toes was seen. There was no use of accessory muscles of ventilation; auscultation revealed bronchial breath sounds in the right upper lung fields and diffuse, faint rhonchi during the expiratory phase. Her heart sounds were regular, and no murmur was noted. Hypermobility was present in the joints of the hands and arms. The remainder of the examination was normal.
Pulmonary-function testing was performed. The forced expiratory volume in 1 second (FEV1) was 23% of the predicted value, the forced vital capacity (FVC) was 45% of the predicted value, and the ratio of FEV1 to FVC was 44%. The total lung capacity was 108% of the predicted value, and the ratio of residual volume to total lung capacity was 65%. The diffusing capacity of the lung for carbon monoxide was 26% of the predicted value.
Dr. Brent P. Little: Contrast-enhanced computed tomography (CT) of the chest revealed hyperinflation of the lungs with severe confluent emphysema and multiple apical bullae (Figure 2A, 2B, and 2C); although diffuse thickening of the bronchial wall and areas of parenchymal air trapping were present, bronchiectasis was notably absent. Normal postsurgical findings included a stump from right upper lobectomy and coil from embolization of a patent ductus arteriosus. The main pulmonary artery was enlarged, measuring 3.8 cm in diameter (Figure 2D).	
Figure 2 
Dr. Mark E. Lindsay: Transthoracic echocardiography revealed dilatation of the right atrium, right ventricle, and inferior vena cava; systolic and diastolic flattening of the interventricular septum (see Video 1, available with the full text of this article at
NEJM.org
); and an estimated right ventricular systolic pressure of 65 mm Hg. The aortic root was not enlarged relative to the patient's body size, and the aortic valve was tricuspid. However, the aortic valve was abnormally thickened and was prolapsed, and there was moderate aortic regurgitation, which had not been present on echocardiograms obtained during infancy. Findings suggestive of constrictive pericarditis, including a septal bounce and respiratory variation across the mitral valve, were also seen.
Dr. Bartley: Empirical prednisone and amoxicillin-clavulanic acid were prescribed, and a diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's history of repeated respiratory illnesses, decreased breath sounds at the apex of the right lung, and chest radiography findings suggestive of congenital lobar emphysema of the right upper lobe suggest a chronic lung condition. The patient's symptoms of chest pain, cough, and dyspnea on exertion, along with the findings of hyperinflation of the lungs with severe confluent emphysema and multiple apical bullae on CT scan, further support this. The absence of bronchiectasis and the presence of diffuse thickening of the bronchial wall and areas of parenchymal air trapping suggest a diagnosis of bronchiolitis obliterans. This is further supported by the patient's pulmonary function test results, which show a decreased FEV1 and FVC, and an increased total lung capacity and ratio of residual volume to total lung capacity, consistent with an obstructive lung disease. The patient's history of bronchiolitis at a young age could have led to the development of bronchiolitis obliterans. \n\nDiagnosis: Bronchiolitis obliterans.""
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        ""content"": ""The patient has a history of repeated respiratory illnesses, decreased breath sounds at the apex of the right lung, and chest radiography revealed findings suggestive of congenital lobar emphysema of the right upper lobe. Histopathological examination of lung specimens revealed lobar emphysema of the right upper and middle lobes that was characterized by the presence of fewer alveoli than the number typically seen in normal lung tissue and hyperinflation of the existing alveoli. The patient also has a history of spontaneous pneumothorax. The patient's symptoms of chest pain, cough, and dyspnea on exertion, along with the findings of hyperinflation of the lungs with severe confluent emphysema and multiple apical bullae on CT, and dilatation of the right atrium, right ventricle, and inferior vena cava on echocardiography, all point towards a diagnosis of severe emphysema. \n\nDiagnosis: Severe Emphysema.""
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        ""content"": ""This is a young woman with a history of congenital lobar emphysema, recurrent respiratory illnesses, and recent symptoms of chest pain, cough, and dyspnea on exertion. Her symptoms and history suggest a chronic lung disease. The differential diagnosis includes chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, and alpha-1 antitrypsin deficiency. However, her alpha-1 antitrypsin test was negative, ruling out alpha-1 antitrypsin deficiency. Her CT scan did not show bronchiectasis, making this diagnosis less likely. Cystic fibrosis typically presents with recurrent respiratory infections and malabsorption, but this patient does not have gastrointestinal symptoms, making cystic fibrosis less likely. Her pulmonary function tests show severe obstruction and hyperinflation, which are characteristic of COPD. However, COPD is typically caused by long-term exposure to lung irritants, such as smoking, and this patient does not have a history of smoking or other environmental exposures. Her history of congenital lobar emphysema, recurrent respiratory illnesses, and the CT findings of severe confluent emphysema and multiple apical bullae suggest a diagnosis of primary ciliary dyskinesia. This is a rare genetic disorder that affects the cilia lining the respiratory tract, leading to recurrent respiratory infections and progressive lung disease. \n\nDiagnosis: Primary Ciliary Dyskinesia.""
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10.1056/NEJMcpc1900590,Case 27-2019: A 16-Year-Old Girl with Head Trauma during a Sailboat Race,,"Concussion, benign paroxysmal positional vertigo, and attention deficit–hyperactivity disorder.",Concussion (consistent with a vestibular and ocular phenotype).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 16-year-old girl was seen in the sports concussion clinic at this hospital because of headache, dizziness, balance problems, fatigue, irritability, and difficulties with sleep and concentration after she had head trauma during a sailboat race.
The patient had been well until 11 days before this evaluation, when she was racing in a regatta and was struck in the head by the boom of another team's boat. On collision, her team's boat capsized. The patient was reportedly dazed and confused, but she was assisted back into the boat by her teammates and they continued to sail. Shortly thereafter, the weather became windy and the patient and her teammates were again knocked out of the boat. The patient reportedly lost consciousness for several minutes; it was suspected but not confirmed that she had been hit by the boom of her team's boat. She was rescued and brought to shore. On arrival of emergency medical services personnel, she was awake and talking but confused. She was transported by ambulance to the emergency department at another hospital. During the ambulance ride, she was agitated and resisted care.
In the emergency department, the patient reported that she felt confused, dizzy, and unsteady and had a headache. The results of a neurologic examination and an examination of the neck were reportedly normal, as were radiographs of the cervical spine. Rest and observation were recommended, and the patient was discharged home in the care of her parents.
Eleven days later, the patient was seen in the sports concussion clinic at this hospital. She did not remember the sailing accident or the subsequent ambulance ride. Since discharge, she had been resting at home with limited activity and stimulation. She had occasional frontotemporal headaches with sharp pain, which she rated at 3 on a scale of 0 to 10, with 10 indicating the most severe pain. She also reported dizziness, balance problems, fatigue, and difficulty sleeping. The patient noted that she had had difficulty concentrating on her summer reading assignment and could not read a full page without losing focus, although she could read less challenging material for 15-to-20-minute intervals. Reading precipitated headaches. She reported that she felt irritable and impatient with having to stay home and that her symptoms decreased with activity.
The patient had a history of several sports-related injuries. When she was 13 years of age, she had a concussion without loss of consciousness after being hit in the head with a paddleboard. After that injury, she was dizzy for several days and had headaches for 3 months. The patient took no medications and had no known allergies. She lived with her parents and brother in a suburban area of New England and was an excellent student. Her brother had attention deficit-hyperactivity disorder (ADHD). There was no family history of headaches, learning disabilities, depression, anxiety, or seizure disorders.
On examination, the patient was alert and answered questions appropriately. On a mental-status examination, orientation, immediate and delayed recall, attention, and language were intact. The neck was not tender and had a full range of motion. Cranial nerves II through XII were normal, and there was no nystagmus. Photophobia was present, and there was pain with upward gaze; the near point of convergence was 15 cm. Both nodding and side-to-side movements of the head caused dizziness. On a Romberg test, the patient swayed mildly when she stood with her feet together and eyes closed. There were mild difficulties with double-leg, single-leg, and tandem stance on a hard surface. The remainder of the physical examination was normal. A diagnosis and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 16-year-old girl was seen in the sports concussion clinic at this hospital because of headache, dizziness, balance problems, fatigue, irritability, and difficulties with sleep and concentration after she had head trauma during a sailboat race.
The patient had been well until 11 days before this evaluation, when she was racing in a regatta and was struck in the head by the boom of another team's boat. On collision, her team's boat capsized. The patient was reportedly dazed and confused, but she was assisted back into the boat by her teammates and they continued to sail. Shortly thereafter, the weather became windy and the patient and her teammates were again knocked out of the boat. The patient reportedly lost consciousness for several minutes; it was suspected but not confirmed that she had been hit by the boom of her team's boat. She was rescued and brought to shore. On arrival of emergency medical services personnel, she was awake and talking but confused. She was transported by ambulance to the emergency department at another hospital. During the ambulance ride, she was agitated and resisted care.
In the emergency department, the patient reported that she felt confused, dizzy, and unsteady and had a headache. The results of a neurologic examination and an examination of the neck were reportedly normal, as were radiographs of the cervical spine. Rest and observation were recommended, and the patient was discharged home in the care of her parents.
Eleven days later, the patient was seen in the sports concussion clinic at this hospital. She did not remember the sailing accident or the subsequent ambulance ride. Since discharge, she had been resting at home with limited activity and stimulation. She had occasional frontotemporal headaches with sharp pain, which she rated at 3 on a scale of 0 to 10, with 10 indicating the most severe pain. She also reported dizziness, balance problems, fatigue, and difficulty sleeping. The patient noted that she had had difficulty concentrating on her summer reading assignment and could not read a full page without losing focus, although she could read less challenging material for 15-to-20-minute intervals. Reading precipitated headaches. She reported that she felt irritable and impatient with having to stay home and that her symptoms decreased with activity.
The patient had a history of several sports-related injuries. When she was 13 years of age, she had a concussion without loss of consciousness after being hit in the head with a paddleboard. After that injury, she was dizzy for several days and had headaches for 3 months. The patient took no medications and had no known allergies. She lived with her parents and brother in a suburban area of New England and was an excellent student. Her brother had attention deficit-hyperactivity disorder (ADHD). There was no family history of headaches, learning disabilities, depression, anxiety, or seizure disorders.
On examination, the patient was alert and answered questions appropriately. On a mental-status examination, orientation, immediate and delayed recall, attention, and language were intact. The neck was not tender and had a full range of motion. Cranial nerves II through XII were normal, and there was no nystagmus. Photophobia was present, and there was pain with upward gaze; the near point of convergence was 15 cm. Both nodding and side-to-side movements of the head caused dizziness. On a Romberg test, the patient swayed mildly when she stood with her feet together and eyes closed. There were mild difficulties with double-leg, single-leg, and tandem stance on a hard surface. The remainder of the physical examination was normal. A diagnosis and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of headache, dizziness, balance problems, fatigue, irritability, and difficulties with sleep and concentration began after she experienced head trauma during a sailboat race. She also reported a history of a previous concussion. These symptoms are consistent with post-concussion syndrome, which can occur after a head injury and can last for weeks or months. The patient's symptoms are not severe enough to suggest a more serious brain injury, and her physical examination was largely normal, which is also consistent with post-concussion syndrome.\n\nDiagnosis: Post-Concussion Syndrome""
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        ""content"": ""The patient is a 16-year-old girl presenting with headache, dizziness, balance problems, fatigue, irritability, difficulties with sleep and concentration following a head trauma during a sailboat race. The differential diagnosis for this patient includes concussion, post-concussion syndrome, traumatic brain injury, and intracranial hemorrhage. The patient's symptoms started after a head trauma, which makes concussion a likely diagnosis. The patient's symptoms have persisted for 11 days, which is longer than the typical duration of symptoms for a concussion, making post-concussion syndrome a possibility. The patient's symptoms are not severe enough to suggest a traumatic brain injury. The patient's symptoms are also not severe enough to suggest an intracranial hemorrhage, and she had a normal neurologic examination in the emergency department after the injury. The patient's symptoms are consistent with post-concussion syndrome, which is a complex disorder in which various symptoms \u2014 such as headaches and dizziness \u2014 last for weeks and sometimes months after the injury that caused the concussion.\n\nDiagnosis: Post-concussion syndrome.""
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10.1056/NEJMcpc1904043,Case 26-2019: A 27-Year-Old Woman with Opioid Use Disorder and Suicidal Ideation,,Opioid use disorder and malingering.,Severe opioid use disorder and malingering (deception syndrome).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 27-year-old woman was evaluated at this hospital because of a suicide attempt.
Approximately 3 months before admission, the patient became homeless and was staying intermittently with friends. Two months before admission, she began to ingest clonazepam daily, and 3 weeks before admission, she began to use intranasal heroin daily. She had depression and anxiety, and 2 days before admission, she expressed that she felt ""tired of living this life"" and wanted ""to end it all.""
On the evening of presentation, the patient reportedly smashed her cell phone on the ground and ate the glass shards as a suicide attempt. Nausea and diffuse abdominal discomfort developed, and she reportedly had an episode vomiting, with the vomit containing 2 teaspoons (10 ml) of blood. Three hours after the ingestion, she presented to the emergency department of this hospital with throat, chest, and abdominal pain. She reported that she had ""regret"" about the ingestion and wanted ""help"" with her substance use and suicidality.
The patient reported past sexual trauma but did not provide details; she did not report any previous suicide attempts, homicidal ideation, or hallucinations. A limited review of systems was notable for anorexia, diaphoresis, diarrhea, impaired sleep, fatigue, mood lability, nightmares, and flashbacks. Her psychiatric history included polysubstance use disorder (with the use of intravenous heroin, fentanyl, benzodiazepines, and cocaine), cutting behavior during adolescence, and anxiety and depression. She had never undergone psychiatric treatment or hospitalization. Her medical history included hepatitis C virus infection, obesity, genital herpes simplex virus infection, and a low-grade squamous intraepithelial lesion of the cervix; in addition, a motor vehicle collision had led to open reduction and internal fixation involving the left arm. She took no medications and had no known adverse reactions to medications. She worked in a local store and had a small child. She had smoked one and a half packs of cigarettes daily for the past 10 years and was a current smoker. She drank 1 pint of vodka daily and reported no history of withdrawals or blackouts. Multiple relatives, including both of her parents, had a history of substance use disorder.
On examination, the temperature was 36.8[degrees]C, the pulse 70 beats per minute, and the oxygen saturation 96% while the patient was breathing ambient air. She appeared disheveled, tearful, and anxious. Abdominal examination revealed mild tenderness on the right side on palpation. On examination by a psychiatrist, she had limited eye contact and mumbling speech, along with poor concentration, depressed mood with a congruent affect, and poor insight and judgment. The complete blood count and levels of electrolytes, urea nitrogen, creatinine, lactate, bilirubin, alkaline phosphatase, and albumin were normal; the aspartate aminotransferase level was 162 U per liter (reference range, 9 to 32), and the alanine aminotransferase level was 52 U per liter (reference range, 7 to 33). Ethanol was not detected in the blood, and human chorionic gonadotropin was not detected in the urine. A urine toxicology screen was positive for opioids and cocaine metabolites. The findings on an electrocardiogram were normal and unchanged from a tracing obtained 10 years earlier.
Dr. Efren J. Flores: The results of radiography of the neck, chest, and abdomen were normal, without a visible radiopaque foreign body. Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material (Figure 1), revealed gallbladder wall thickening and trace perihepatic fluid. These findings can be seen in patients with acute hepatitis. There was no evidence of pneumoperitoneum or of a radiopaque foreign body.	
Figure 1 
Dr. Cruz: Intravenous normal saline, morphine sulfate, and piperacillin-tazobactam were administered. The patient was evaluated by the surgery and psychiatry services. Because of concern about the patient's risk of self-harm, an order that authorized temporary involuntary hospitalization was implemented.
The next evening, the patient reported that while she was trying to get out of a stretcher, she ""heard a pop"" in her right elbow, which was accompanied by immediate pain without any numbness or tingling. On examination by an orthopedic surgeon, the olecranon process appeared to protrude posteriorly and medially without ecchymosis. The patient was not able to move the arm at the elbow, although range of motion was intact at the shoulder and wrist.
Dr. Flores: A lateral image of the right elbow (Figure 2A) showed posterior dislocation of the elbow with impaction of the olecranon process of the ulna into the distal humerus outside the olecranon fossa. An anteroposterior image of the right elbow (Figure 2B) confirmed dislocation of the elbow with malalignment of the ulnotrochlear and radiocapitellar joints.	
Figure 2
Dr. Cruz: After the administration of acetaminophen, ibuprofen, oxycodone, and intravenous morphine, the elbow was manually reduced and a splint was applied. Additional radiographic images were obtained.
Dr. Flores: Lateral and anteroposterior images of the right elbow obtained after closed reduction and splinting (Figure 2C and 2D) showed normal alignment of the ulnotrochlear and radiocapitellar joints.
Dr. Cruz: During the next 18 hours, the patient remained under observation, with a plan for transfer to an inpatient psychiatric hospital for ongoing care. One hour before transfer, the patient went to the bathroom without her observer and then reported that she could not move her right arm.
Dr. Flores: A lateral image of the right elbow showed that the splint was in place and showed posterior dislocation of the elbow with impaction of the olecranon process of the ulna into the distal humerus outside the olecranon fossa. An anteroposterior image of the right elbow confirmed dislocation of the elbow with predominant involvement of the radiocapitellar joint. There was irregularity of the radial head and lateral humeral epicondyle that was consistent with a nondisplaced fracture.
Dr. Cruz: Intravenous morphine was administered. The elbow was again reduced, and a circumferential fiberglass cast was placed.
Dr. Flores: A lateral image of the right elbow obtained after the second closed reduction and casting showed normal alignment and the presence of a cast.
Dr. Cruz: The next afternoon, after the plan for transfer to a psychiatric hospital was shared with the patient, she was found in the bathroom without her observer, where she was banging her left arm against the wall. She reported pain, and oral oxycodone and intramuscular hydromorphone were administered.
Dr. Flores: A lateral image of the left elbow obtained hours after the second reduction and casting of the right elbow (Figure 2E) showed posterior dislocation of the left elbow and a fragment from a displaced fracture of the trochlea. There were two screws in the lateral humeral epicondyle from previous open reduction and internal fixation.
Dr. Cruz: Intraarticular nerve block was performed. The left elbow was reduced, and a long-arm circumferential fiberglass cast was placed.
Additional management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 27-year-old woman was evaluated at this hospital because of a suicide attempt.
Approximately 3 months before admission, the patient became homeless and was staying intermittently with friends. Two months before admission, she began to ingest clonazepam daily, and 3 weeks before admission, she began to use intranasal heroin daily. She had depression and anxiety, and 2 days before admission, she expressed that she felt ""tired of living this life"" and wanted ""to end it all.""
On the evening of presentation, the patient reportedly smashed her cell phone on the ground and ate the glass shards as a suicide attempt. Nausea and diffuse abdominal discomfort developed, and she reportedly had an episode vomiting, with the vomit containing 2 teaspoons (10 ml) of blood. Three hours after the ingestion, she presented to the emergency department of this hospital with throat, chest, and abdominal pain. She reported that she had ""regret"" about the ingestion and wanted ""help"" with her substance use and suicidality.
The patient reported past sexual trauma but did not provide details; she did not report any previous suicide attempts, homicidal ideation, or hallucinations. A limited review of systems was notable for anorexia, diaphoresis, diarrhea, impaired sleep, fatigue, mood lability, nightmares, and flashbacks. Her psychiatric history included polysubstance use disorder (with the use of intravenous heroin, fentanyl, benzodiazepines, and cocaine), cutting behavior during adolescence, and anxiety and depression. She had never undergone psychiatric treatment or hospitalization. Her medical history included hepatitis C virus infection, obesity, genital herpes simplex virus infection, and a low-grade squamous intraepithelial lesion of the cervix; in addition, a motor vehicle collision had led to open reduction and internal fixation involving the left arm. She took no medications and had no known adverse reactions to medications. She worked in a local store and had a small child. She had smoked one and a half packs of cigarettes daily for the past 10 years and was a current smoker. She drank 1 pint of vodka daily and reported no history of withdrawals or blackouts. Multiple relatives, including both of her parents, had a history of substance use disorder.
On examination, the temperature was 36.8[degrees]C, the pulse 70 beats per minute, and the oxygen saturation 96% while the patient was breathing ambient air. She appeared disheveled, tearful, and anxious. Abdominal examination revealed mild tenderness on the right side on palpation. On examination by a psychiatrist, she had limited eye contact and mumbling speech, along with poor concentration, depressed mood with a congruent affect, and poor insight and judgment. The complete blood count and levels of electrolytes, urea nitrogen, creatinine, lactate, bilirubin, alkaline phosphatase, and albumin were normal; the aspartate aminotransferase level was 162 U per liter (reference range, 9 to 32), and the alanine aminotransferase level was 52 U per liter (reference range, 7 to 33). Ethanol was not detected in the blood, and human chorionic gonadotropin was not detected in the urine. A urine toxicology screen was positive for opioids and cocaine metabolites. The findings on an electrocardiogram were normal and unchanged from a tracing obtained 10 years earlier.
Dr. Efren J. Flores: The results of radiography of the neck, chest, and abdomen were normal, without a visible radiopaque foreign body. Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material (Figure 1), revealed gallbladder wall thickening and trace perihepatic fluid. These findings can be seen in patients with acute hepatitis. There was no evidence of pneumoperitoneum or of a radiopaque foreign body.	
Figure 1 
Dr. Cruz: Intravenous normal saline, morphine sulfate, and piperacillin-tazobactam were administered. The patient was evaluated by the surgery and psychiatry services. Because of concern about the patient's risk of self-harm, an order that authorized temporary involuntary hospitalization was implemented.
The next evening, the patient reported that while she was trying to get out of a stretcher, she ""heard a pop"" in her right elbow, which was accompanied by immediate pain without any numbness or tingling. On examination by an orthopedic surgeon, the olecranon process appeared to protrude posteriorly and medially without ecchymosis. The patient was not able to move the arm at the elbow, although range of motion was intact at the shoulder and wrist.
Dr. Flores: A lateral image of the right elbow (Figure 2A) showed posterior dislocation of the elbow with impaction of the olecranon process of the ulna into the distal humerus outside the olecranon fossa. An anteroposterior image of the right elbow (Figure 2B) confirmed dislocation of the elbow with malalignment of the ulnotrochlear and radiocapitellar joints.	
Figure 2
Dr. Cruz: After the administration of acetaminophen, ibuprofen, oxycodone, and intravenous morphine, the elbow was manually reduced and a splint was applied. Additional radiographic images were obtained.
Dr. Flores: Lateral and anteroposterior images of the right elbow obtained after closed reduction and splinting (Figure 2C and 2D) showed normal alignment of the ulnotrochlear and radiocapitellar joints.
Dr. Cruz: During the next 18 hours, the patient remained under observation, with a plan for transfer to an inpatient psychiatric hospital for ongoing care. One hour before transfer, the patient went to the bathroom without her observer and then reported that she could not move her right arm.
Dr. Flores: A lateral image of the right elbow showed that the splint was in place and showed posterior dislocation of the elbow with impaction of the olecranon process of the ulna into the distal humerus outside the olecranon fossa. An anteroposterior image of the right elbow confirmed dislocation of the elbow with predominant involvement of the radiocapitellar joint. There was irregularity of the radial head and lateral humeral epicondyle that was consistent with a nondisplaced fracture.
Dr. Cruz: Intravenous morphine was administered. The elbow was again reduced, and a circumferential fiberglass cast was placed.
Dr. Flores: A lateral image of the right elbow obtained after the second closed reduction and casting showed normal alignment and the presence of a cast.
Dr. Cruz: The next afternoon, after the plan for transfer to a psychiatric hospital was shared with the patient, she was found in the bathroom without her observer, where she was banging her left arm against the wall. She reported pain, and oral oxycodone and intramuscular hydromorphone were administered.
Dr. Flores: A lateral image of the left elbow obtained hours after the second reduction and casting of the right elbow (Figure 2E) showed posterior dislocation of the left elbow and a fragment from a displaced fracture of the trochlea. There were two screws in the lateral humeral epicondyle from previous open reduction and internal fixation.
Dr. Cruz: Intraarticular nerve block was performed. The left elbow was reduced, and a long-arm circumferential fiberglass cast was placed.
Additional management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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10.1056/NEJMcpc1900596,"Case 25-2019: A 41-Year-Old Pregnant Woman with Abdominal Pain
","Hemoglobin (g/dl)  12.5
Hematocrit (%)  37.5
Platelet count (per mm3
)   160,000
White-cell count (per mm3)   14,300
Differential count (%)
Neutrophils 85.9
Lymphocytes 7.2
Monocytes 6.5
Eosinophils 0.1
Basophils 0.1
Immature granulocytes 0.2
Sodium (mmol/liter)  136
Potassium (mmol/liter)  3.5
Chloride (mmol/liter) 98–107 99
Carbon dioxide (mmol/liter)   20
Anion gap (mmol/liter)  18
Urea nitrogen (mg/dl)  7
Creatinine (mg/dl)  0.6
Fasting glucose (mg/dl)  0 111
Aspartate aminotransferase (U/liter) 17
Alanine aminotransferase (U/liter)  13
Alkaline phosphatase (U/liter)  116
Total bilirubin (mg/dl)  0.4
Total protein (g/dl)  6.9
Albumin (g/dl) 4.  3.5
Lipase (U/liter)  25",Acute suppurative appendicitis and periappendicitis.,Appendicitis during pregnancy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 41-year-old pregnant woman was seen in the emergency department of this hospital at 36 weeks 3 days of gestation because of abdominal pain.
Six and a half months before this evaluation, when the patient was at her initial routine prenatal visit, transvaginal ultrasonography revealed a normal intrauterine gestational sac and embryo. The date of the last menstrual period was unknown, and ultrasonographic measurements were used to determine the estimated due date. Thereafter, prenatal follow-up was uneventful.
Fifteen hours before the current evaluation, abdominal pain developed suddenly after the patient had eaten breakfast. The pain was in the right lower quadrant and was described as sharp and constant. She rated the pain at 8 on a scale of 0 to 10, with 10 indicating the most severe pain; she noted that the pain was more severe than it had been during her two previous vaginal deliveries, which had occurred without epidural anesthesia. She had no fever, chills, diarrhea, dysuria, hematuria, vaginal bleeding, or contractions, and fetal movement was normal. The patient took oral docusate, which did not relieve the pain, and then took acetaminophen, after which the pain decreased slightly. She called her obstetrician, who recommended that she present to the clinic for evaluation.
In the obstetrics clinic, transabdominal and transvaginal ultrasonography were performed. The fetus was in cephalic presentation, with a biophysical profile score of 8/8 (indicating normal fetal well-being) and a fetal heart rate of 134 beats per minute. The placenta was positioned anteriorly, the cervical length was 21 mm, and the umbilical artery appeared normal on Doppler examination. The patient was referred to the emergency department of a local hospital for further evaluation and arrived approximately 7 hours after the onset of symptoms.
In the emergency department of the other hospital, the patient reported that the abdominal pain persisted and that nausea had developed. Her surgical history consisted of breast augmentation surgery and extraction of wisdom teeth in the distant past. She was gravida 4, 2-0-1-2. Her first and third pregnancies had been uncomplicated and had resulted in vaginal deliveries at full term; the second pregnancy had ended in a spontaneous abortion. She was immune to varicella and rubella; tests performed during this pregnancy for syphilis, hepatitis B virus surface antigen, gonorrhea, chlamydia, human immunodeficiency virus, and group B streptococcus had been negative. The patient was taking prenatal vitamins and was allergic to iodine-containing contrast material, which had caused anaphylaxis. She lived with her husband and two children in a suburban neighborhood in New England. She did not drink alcohol, smoke tobacco, or use illicit drugs. Her father had died of liver disease associated with alcohol use disorder; her mother had had cervical cancer and hypertension and had died of a ruptured cerebral aneurysm.
On examination, the temperature was 36.7[degrees]C, the pulse 71 beats per minute, the blood pressure 113/67 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The abdomen was gravid and soft, with hyperactive bowel sounds; on palpation, there was severe tenderness in the right lower quadrant that extended inferiorly to the inguinal region, with voluntary guarding and without rebound tenderness. Rovsing's sign (pain in the right lower quadrant with palpation of the left lower quadrant) was present. A limited pelvic examination revealed that the cervix was closed, and the remainder of the examination was normal. Urinalysis showed cloudy, yellow urine, with a specific gravity of 1.002, moderate ketones, and few bacteria. The blood type was O, Rh-positive; other laboratory test results are shown in Table 1.	
Table 1 
Acetaminophen and ondansetron were administered orally and normal saline intravenously. An imaging study was obtained; after the results were available, ampicillin-sulbactam and clindamycin were administered intravenously, and the patient was transferred by ambulance to the emergency department of this hospital for further treatment.
Management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 41-year-old pregnant woman was seen in the emergency department of this hospital at 36 weeks 3 days of gestation because of abdominal pain.
Six and a half months before this evaluation, when the patient was at her initial routine prenatal visit, transvaginal ultrasonography revealed a normal intrauterine gestational sac and embryo. The date of the last menstrual period was unknown, and ultrasonographic measurements were used to determine the estimated due date. Thereafter, prenatal follow-up was uneventful.
Fifteen hours before the current evaluation, abdominal pain developed suddenly after the patient had eaten breakfast. The pain was in the right lower quadrant and was described as sharp and constant. She rated the pain at 8 on a scale of 0 to 10, with 10 indicating the most severe pain; she noted that the pain was more severe than it had been during her two previous vaginal deliveries, which had occurred without epidural anesthesia. She had no fever, chills, diarrhea, dysuria, hematuria, vaginal bleeding, or contractions, and fetal movement was normal. The patient took oral docusate, which did not relieve the pain, and then took acetaminophen, after which the pain decreased slightly. She called her obstetrician, who recommended that she present to the clinic for evaluation.
In the obstetrics clinic, transabdominal and transvaginal ultrasonography were performed. The fetus was in cephalic presentation, with a biophysical profile score of 8/8 (indicating normal fetal well-being) and a fetal heart rate of 134 beats per minute. The placenta was positioned anteriorly, the cervical length was 21 mm, and the umbilical artery appeared normal on Doppler examination. The patient was referred to the emergency department of a local hospital for further evaluation and arrived approximately 7 hours after the onset of symptoms.
In the emergency department of the other hospital, the patient reported that the abdominal pain persisted and that nausea had developed. Her surgical history consisted of breast augmentation surgery and extraction of wisdom teeth in the distant past. She was gravida 4, 2-0-1-2. Her first and third pregnancies had been uncomplicated and had resulted in vaginal deliveries at full term; the second pregnancy had ended in a spontaneous abortion. She was immune to varicella and rubella; tests performed during this pregnancy for syphilis, hepatitis B virus surface antigen, gonorrhea, chlamydia, human immunodeficiency virus, and group B streptococcus had been negative. The patient was taking prenatal vitamins and was allergic to iodine-containing contrast material, which had caused anaphylaxis. She lived with her husband and two children in a suburban neighborhood in New England. She did not drink alcohol, smoke tobacco, or use illicit drugs. Her father had died of liver disease associated with alcohol use disorder; her mother had had cervical cancer and hypertension and had died of a ruptured cerebral aneurysm.
On examination, the temperature was 36.7[degrees]C, the pulse 71 beats per minute, the blood pressure 113/67 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The abdomen was gravid and soft, with hyperactive bowel sounds; on palpation, there was severe tenderness in the right lower quadrant that extended inferiorly to the inguinal region, with voluntary guarding and without rebound tenderness. Rovsing's sign (pain in the right lower quadrant with palpation of the left lower quadrant) was present. A limited pelvic examination revealed that the cervix was closed, and the remainder of the examination was normal. Urinalysis showed cloudy, yellow urine, with a specific gravity of 1.002, moderate ketones, and few bacteria. The blood type was O, Rh-positive; other laboratory test results are shown in Table 1.	
Table 1 
Acetaminophen and ondansetron were administered orally and normal saline intravenously. An imaging study was obtained; after the results were available, ampicillin-sulbactam and clindamycin were administered intravenously, and the patient was transferred by ambulance to the emergency department of this hospital for further treatment.
Management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a pregnant woman presenting with severe right lower quadrant abdominal pain. The pain is described as sharp and constant, and is more severe than her previous labor pains. She has no fever, chills, diarrhea, dysuria, hematuria, vaginal bleeding, or contractions, and fetal movement is normal. The patient's urinalysis showed moderate ketones and few bacteria, which could indicate a urinary tract infection, but the severity and location of the pain suggest another cause. The patient's pain is localized to the right lower quadrant, which is where the appendix is located. The presence of Rovsing's sign, which is pain in the right lower quadrant upon palpation of the left lower quadrant, is a classic sign of appendicitis. The patient's symptoms, physical examination findings, and urinalysis results are all consistent with a diagnosis of appendicitis.\n\nDiagnosis: Appendicitis.""
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        ""content"": ""The patient is a 41-year-old pregnant woman presenting with severe right lower quadrant abdominal pain. The differential diagnosis for this patient includes appendicitis, ectopic pregnancy, ovarian torsion, and kidney stones. The patient's pain is severe and constant, which is not characteristic of labor pain. The patient is not experiencing contractions, vaginal bleeding, or changes in fetal movement, which makes preterm labor or placental abruption less likely. The patient's ultrasound shows a normal fetus and placenta, which makes ectopic pregnancy and placental abruption less likely. The patient's urinalysis shows moderate ketones and few bacteria, which is not indicative of a urinary tract infection or kidney stones. The patient's pain is localized to the right lower quadrant and is severe, which is characteristic of appendicitis. The patient also has a positive Rovsing's sign, which is indicative of appendicitis. \n\nDiagnosis: Appendicitis.""
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10.1056/NEJMcpc1900142,"Case 24-2019: A 39-Year-Old Woman with Palpitations, Abdominal Pain, and Vomiting","Hematocrit (%)  27.9 36.9
Hemoglobin (g/dl)  9.5 12.7
White-cell count (per mm3) 400 ,000 3730 10,030
Differential count (%)
Neutrophils   83.3 84.7
Immature granulocytes 0.3 0.4
Lymphocytes   11.6 9.5
Monocytes   4.7 5.4
Basophils   0.0 0.0
Eosinophils   0.1 0.0
Platelet count (per mm3
) 135,00 0,000 209,000 413,000
Red-cell count (per mm3
)  3,420,000 4,640,000
Mean corpuscular volume (fl)   81.6 79.5
Red-cell distribution width (%)  12.4 13.2
Prothrombin time (sec)   12.8
Prothrombin-time international 
normalized ratio
  1.2
Troponin T (ng/ml) 0–0.01  
Lactate (mmol/liter) 0.5–1.9 0.9 1.3
Sodium (mmol/liter)   144 139
Potassium (mmol/liter) 3.5–5.2 3.7 3.5
Chloride (mmol/liter) 95–106 108 90
Carbon dioxide (mmol/liter) 2 1 24 19
Anion gap (mmol/liter)   12 30
Urea nitrogen (mg/dl)   4 12
Creatinine (mg/dl)   0.31 0.51
Estimated glomerular filtration rate 
(ml/min/1.73 m2)‡
>60 >60 >60
Glucose (mg/dl)   108 94
Calcium (mg/dl) 8.7–10.4 8.7 9.4",Hyperthyroidism due to Graves' disease.,Hyperthyroidism,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 39-year-old woman with cyclic vomiting syndrome and polysubstance use disorder was seen in the emergency department of this hospital because of abdominal pain and vomiting.
Eleven weeks before the current presentation, the patient was admitted to a hospital affiliated with this hospital because of intractable nausea and vomiting. She also had loose stools and pain in the right lower abdomen in the presence of menses. Her symptoms were similar to those in previous episodes that had been attributed to cyclic vomiting syndrome. Testing for Clostridium difficile toxin and fecal leukocytes was negative, as was an examination of the stool for ova and parasites; a stool culture showed normal enteric flora. A urine toxicology screen was positive for cocaine and opiates. Imaging studies were obtained.
Dr. Mark A. Anderson: Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed bilateral, punctate, nonobstructing renal calculi without hydronephrosis. There was no evidence of bowel obstruction or acute inflammation in the abdomen or pelvis, including the appendix. Normal premenopausal ovaries that contained functional follicles were noted.
Dr. Hills-Evans: Ondansetron, hydromorphone, and intravenous fluids were administered. Nausea, vomiting, and abdominal pain resolved. On the second hospital day, the patient was able to eat normally and was discharged home.
One day before the current presentation, the patient inhaled smoke from an electrical fire in her basement. After the smoke inhalation, pain in the left lower abdomen and severe fatigue developed, but she did not seek medical evaluation. On the day of the current presentation, menses began, and she awoke with nausea and profuse vomiting of dark-brown fluid. Her temperature at home was 39.4[degrees]C. During the next 12 hours, she had persistent nausea and repeated episodes of vomiting. Weakness, light-headedness, and dizziness developed, and she presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported ongoing nausea, vomiting, and pain in the left lower abdomen. She reported recent use of cannabinoids but no other drugs. Other medical history included nephrolithiasis, asthma, allergic rhinitis, chronic back pain, depression, gastroesophageal reflux disease, and severe dysmenorrhea. Past surgeries included shoulder replacement, reduction mammoplasty, and removal of an ovarian cyst. Medications included acetaminophen, intranasal fluticasone, inhaled fluticasone propionate, albuterol, promethazine, ondansetron, polyethylene glycol, and a multivitamin. She had no known allergies. She did not know of any medical problems in her family. Three years before presentation, she had moved to New England from the northwestern United States after marrying her husband. She had worked in the pharmaceutical industry but had stopped working 3 months previously because of cyclic vomiting syndrome. She did not use tobacco or alcohol. She had a history of using cocaine, heroin, marijuana, and 3,4-methylenedioxymethamphetamine (MDMA).
The temperature was 37.2[degrees]C, the pulse 165 beats per minute, the blood pressure 152/70 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The weight was 52.5 kg; at the affiliated hospital 11 weeks earlier, it had been 59.3 kg. She was alert and oriented but had a labile affect, with alternating periods of laughing and crying. Her gaze was noted to be intense, and her speech was rapid, pressured, and at times slurred. She was agitated and was seen thrashing in her bed, pulling at equipment and clothing. Her face and chest were erythematous, and her skin was warm to the touch. A fine tremor was noted in her hands, but no tongue fasciculations were seen. She did not cooperate during a neck examination. The heart sounds were rapid and regular; a systolic ejection murmur was noted. The abdomen was soft, with normal bowel sounds and no distention; there was tenderness on palpation of the left lower abdomen.
Shortly after arrival in the emergency department, the patient vomited ""coffee grounds"" material. Twenty-five minutes later, the pulse increased from 165 beats per minute to 210 beats per minute.
Dr. Conor D. Barrett: A 12-lead electrocardiogram obtained in the emergency department showed supraventricular tachycardia with a long RP interval (Figure 1A, and Fig. S1 in the Supplementary Appendix, available with the full text of this article at
NEJM.org
). Adenosine was administered intravenously, and after a ventricular ectopic beat and a brief episode of atrial ectopy, sinus tachycardia emerged. It is important to note that the last observed event on cessation of this patient's supraventricular tachycardia was a QRS complex and not a P wave, and the previously observed P wave was of high-to-low atrial activation, as seen in lead II (Figure 1B). A subsequent 12-lead electrocardiogram confirmed ongoing sinus tachycardia (Figure 1C).	
Figure 1 
Dr. Hills-Evans: The alkaline phosphatase level was 165 U per liter (reference range, 27 to 129); the results of other tests of liver function were normal. A urine test for beta human chorionic gonadotropin was negative. Urinalysis showed a specific gravity of 1.013, with 2+ ketones and 2+ blood per high-power field, as well as 2 leukocytes per high-power field (reference range, 0 to 4). A urine toxicology screen was positive for fentanyl, oxycodone, and cannabinoids. The results of other laboratory tests are shown in Table 1. Additional imaging studies were obtained.	
Table 1 
Dr. Anderson: A chest radiograph showed clear lungs, a normal cardiac silhouette, no pulmonary edema, and no mediastinal or hilar lymphadenopathy. A CT scan of the abdomen and pelvis, obtained after the administration of intravenous contrast material, showed bilateral, punctate, nonobstructing renal calculi without hydronephrosis. During the portal venous phase, the liver attenuation level was 27 Hounsfield units lower than the splenic attenuation level, a finding consistent with hepatic steatosis. There was no bowel obstruction or acute inflammation in the abdomen or pelvis. The appendix appeared normal, and the ovaries were premenopausal, containing functional follicles (Figure 2).	
Figure 2 
Dr. Hills-Evans: Intravenous fluids, ondansetron, pantoprazole, fentanyl, and lorazepam were administered. The patient was admitted to the intensive care unit (ICU), and a diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 39-year-old woman with cyclic vomiting syndrome and polysubstance use disorder was seen in the emergency department of this hospital because of abdominal pain and vomiting.
Eleven weeks before the current presentation, the patient was admitted to a hospital affiliated with this hospital because of intractable nausea and vomiting. She also had loose stools and pain in the right lower abdomen in the presence of menses. Her symptoms were similar to those in previous episodes that had been attributed to cyclic vomiting syndrome. Testing for Clostridium difficile toxin and fecal leukocytes was negative, as was an examination of the stool for ova and parasites; a stool culture showed normal enteric flora. A urine toxicology screen was positive for cocaine and opiates. Imaging studies were obtained.
Dr. Mark A. Anderson: Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed bilateral, punctate, nonobstructing renal calculi without hydronephrosis. There was no evidence of bowel obstruction or acute inflammation in the abdomen or pelvis, including the appendix. Normal premenopausal ovaries that contained functional follicles were noted.
Dr. Hills-Evans: Ondansetron, hydromorphone, and intravenous fluids were administered. Nausea, vomiting, and abdominal pain resolved. On the second hospital day, the patient was able to eat normally and was discharged home.
One day before the current presentation, the patient inhaled smoke from an electrical fire in her basement. After the smoke inhalation, pain in the left lower abdomen and severe fatigue developed, but she did not seek medical evaluation. On the day of the current presentation, menses began, and she awoke with nausea and profuse vomiting of dark-brown fluid. Her temperature at home was 39.4[degrees]C. During the next 12 hours, she had persistent nausea and repeated episodes of vomiting. Weakness, light-headedness, and dizziness developed, and she presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported ongoing nausea, vomiting, and pain in the left lower abdomen. She reported recent use of cannabinoids but no other drugs. Other medical history included nephrolithiasis, asthma, allergic rhinitis, chronic back pain, depression, gastroesophageal reflux disease, and severe dysmenorrhea. Past surgeries included shoulder replacement, reduction mammoplasty, and removal of an ovarian cyst. Medications included acetaminophen, intranasal fluticasone, inhaled fluticasone propionate, albuterol, promethazine, ondansetron, polyethylene glycol, and a multivitamin. She had no known allergies. She did not know of any medical problems in her family. Three years before presentation, she had moved to New England from the northwestern United States after marrying her husband. She had worked in the pharmaceutical industry but had stopped working 3 months previously because of cyclic vomiting syndrome. She did not use tobacco or alcohol. She had a history of using cocaine, heroin, marijuana, and 3,4-methylenedioxymethamphetamine (MDMA).
The temperature was 37.2[degrees]C, the pulse 165 beats per minute, the blood pressure 152/70 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The weight was 52.5 kg; at the affiliated hospital 11 weeks earlier, it had been 59.3 kg. She was alert and oriented but had a labile affect, with alternating periods of laughing and crying. Her gaze was noted to be intense, and her speech was rapid, pressured, and at times slurred. She was agitated and was seen thrashing in her bed, pulling at equipment and clothing. Her face and chest were erythematous, and her skin was warm to the touch. A fine tremor was noted in her hands, but no tongue fasciculations were seen. She did not cooperate during a neck examination. The heart sounds were rapid and regular; a systolic ejection murmur was noted. The abdomen was soft, with normal bowel sounds and no distention; there was tenderness on palpation of the left lower abdomen.
Shortly after arrival in the emergency department, the patient vomited ""coffee grounds"" material. Twenty-five minutes later, the pulse increased from 165 beats per minute to 210 beats per minute.
Dr. Conor D. Barrett: A 12-lead electrocardiogram obtained in the emergency department showed supraventricular tachycardia with a long RP interval (Figure 1A, and Fig. S1 in the Supplementary Appendix, available with the full text of this article at
NEJM.org
). Adenosine was administered intravenously, and after a ventricular ectopic beat and a brief episode of atrial ectopy, sinus tachycardia emerged. It is important to note that the last observed event on cessation of this patient's supraventricular tachycardia was a QRS complex and not a P wave, and the previously observed P wave was of high-to-low atrial activation, as seen in lead II (Figure 1B). A subsequent 12-lead electrocardiogram confirmed ongoing sinus tachycardia (Figure 1C).	
Figure 1 
Dr. Hills-Evans: The alkaline phosphatase level was 165 U per liter (reference range, 27 to 129); the results of other tests of liver function were normal. A urine test for beta human chorionic gonadotropin was negative. Urinalysis showed a specific gravity of 1.013, with 2+ ketones and 2+ blood per high-power field, as well as 2 leukocytes per high-power field (reference range, 0 to 4). A urine toxicology screen was positive for fentanyl, oxycodone, and cannabinoids. The results of other laboratory tests are shown in Table 1. Additional imaging studies were obtained.	
Table 1 
Dr. Anderson: A chest radiograph showed clear lungs, a normal cardiac silhouette, no pulmonary edema, and no mediastinal or hilar lymphadenopathy. A CT scan of the abdomen and pelvis, obtained after the administration of intravenous contrast material, showed bilateral, punctate, nonobstructing renal calculi without hydronephrosis. During the portal venous phase, the liver attenuation level was 27 Hounsfield units lower than the splenic attenuation level, a finding consistent with hepatic steatosis. There was no bowel obstruction or acute inflammation in the abdomen or pelvis. The appendix appeared normal, and the ovaries were premenopausal, containing functional follicles (Figure 2).	
Figure 2 
Dr. Hills-Evans: Intravenous fluids, ondansetron, pantoprazole, fentanyl, and lorazepam were administered. The patient was admitted to the intensive care unit (ICU), and a diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 39-year-old woman with a history of cyclic vomiting syndrome and polysubstance use disorder. She presents with abdominal pain, vomiting, and recent weight loss. She also has a history of nephrolithiasis, asthma, allergic rhinitis, chronic back pain, depression, gastroesophageal reflux disease, and severe dysmenorrhea. Her symptoms are similar to those in previous episodes that had been attributed to cyclic vomiting syndrome. However, her recent exposure to smoke from an electrical fire, her recent use of cannabinoids, and her positive urine toxicology screen for fentanyl, oxycodone, and cannabinoids suggest that her current symptoms may be related to substance use or withdrawal. The differential diagnosis for this patient includes cyclic vomiting syndrome, substance withdrawal, substance intoxication, and other causes of abdominal pain and vomiting such as gastroenteritis, pancreatitis, and peptic ulcer disease. Her CT scan shows no evidence of bowel obstruction or acute inflammation in the abdomen or pelvis, making gastroenteritis, pancreatitis, and peptic ulcer disease less likely. Her symptoms began after inhaling smoke from an electrical fire and using cannabinoids, suggesting that her symptoms may be related to substance use. However, her symptoms are also similar to her previous episodes of cyclic vomiting syndrome, and her urine toxicology screen was positive for fentanyl and oxycodone, suggesting that her symptoms may also be related to substance withdrawal. Given her history of cyclic vomiting syndrome, her recent use of cannabinoids, and her positive urine toxicology screen for fentanyl and oxycodone, the most likely diagnosis is a flare of her cyclic vomiting syndrome triggered by substance use and withdrawal.\n\nDiagnosis: Flare of cyclic vomiting syndrome triggered by substance use and withdrawal.""
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10.1056/NEJMcpc1900598,"Case 23-2019: A 52-Year-Old Man with Fever, Cough, and Hypoxemia
","White-cell count (per mm3
) 400 ,000 17,300   24,510
Hemoglobin (g/dl)   16.5   14.4
Hematocrit (%)   46.9   41.6
Platelet count (per mm3
) 135,00 0,000 307,000   294,000
Neutrophils (%)   85.2  
Sodium (mmol/liter)   138   138
Potassium (mmol/liter) 3.5–5.2 4.6   4.7
Chloride (mmol/liter) 95–106 98   106
Carbon dioxide (mmol/liter) 2 1 23   18
Urea nitrogen (mg/dl) 9–23 24   25
Creatinine (mg/dl) 0.50–1.30 1.80   1.78
Calcium (mg/dl) 9.1   8.1
Lactate (mmol/liter)  2.3   2.0
Troponin T (ng/ml)  0.65 <0.03 0.80
Central venous oxygen saturation (%) 7 0 79.1
Arterial blood gas analysis
Fraction of inspired oxygen 1.0 1.0
pH     7.24 7.31
Partial pressure of carbon dioxide 
(mm Hg)
    48 37
Partial pressure of oxygen (mm Hg)     82 151",Flail mitral valve due to acute myocardial infarction of the papillary muscle in the absence of obstructive coronary artery disease.,Acute mitral regurgitation.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 52-year-old man was transferred to this hospital for evaluation and treatment of hypoxemia.
The patient had been in his usual state of health until 7 days before transfer to this hospital, when nonproductive cough and intermittent fever with temperatures of up to 38.2[degrees]C developed. During the subsequent 4 days, these symptoms persisted and were accompanied by malaise, mild anorexia, weakness, and exertional dyspnea. He had no chest pain, palpitations, antecedent respiratory symptoms, rashes, joint symptoms, or weight loss. The administration of dextromethorphan and acetaminophen did not improve symptoms. On the morning before transfer to this hospital, dyspnea occurred with minimal exertion. The patient presented to a local urgent care clinic, where the heart rate was 113 beats per minute and the oxygen saturation was 91% while he was breathing ambient air. He was referred to the emergency department at a local hospital for further evaluation.
On presentation to the other hospital, the temperature was 37.6[degrees]C, the heart rate 115 beats per minute, the blood pressure 126/83 mm Hg, and the respiratory rate 18 breaths per minute. The oxygen saturation was 90% while the patient was breathing ambient air and then increased to 93% while he was receiving oxygen through a nasal cannula at a rate of 2 liters per minute. No jugular venous distention or increased work of breathing was reported. Auscultation of the chest revealed rhonchi and occasional wheezes on the right side and a prominent systolic murmur at the right upper sternal border. The remainder of the examination was normal. The N-terminal pro-B-type natriuretic peptide level was 4850 pg per milliliter (reference range, 0 to 900), the d-dimer level 2487 ng per milliliter (reference range, <244), and the lactate dehydrogenase level 458 U per liter (reference range, 110 to 210); other laboratory test results are shown in Table 1. Cultures of the blood were obtained.	
Table 1 
Dr. Milena Petranovic: Initial posteroanterior and lateral chest radiographs (Fig. 1A and 1B) showed markedly asymmetric lung opacities located predominantly in the central portion of the right upper lobe.	
Figure 1 
Dr. Rajeev Malhotra: An electrocardiogram (Fig. 2A) showed sinus tachycardia with left axis deviation, left atrial abnormality, early R-wave progression, and ST-segment depressions in the anterior leads. Bedside ultrasonographic examination of the heart revealed a hyperdynamic left ventricle.	
Figure 2 
Dr. Martin: Ceftriaxone, azithromycin, aspirin, atorvastatin, and intravenous normal saline were administered, and the administration of supplemental oxygen through a nasal cannula was continued. The patient was admitted to the intensive care unit (ICU) of the other hospital.
That afternoon, 5 hours after presentation to the other hospital, hypoxemia worsened; the oxygen saturation was 86% while the patient was receiving oxygen through a nasal cannula at a rate of 6 liters per minute, and the respiratory rate was 34 breaths per minute. The levels improved after the administration of additional supplemental oxygen; the oxygen saturation increased to 92% while he was receiving oxygen through a nonrebreather face mask at a rate of 15 liters per minute and then increased to 100% while he was receiving oxygen through a high-flow nasal cannula at a rate of 60 liters per minute (fraction of inspired oxygen [Fio2], 1.0), and the respiratory rate decreased to 28 breaths per minute.
Dr. Petranovic: A portable chest radiograph (Fig. 1C) showed persistent asymmetric lung opacities. Also seen were new septal lines, increased thickening of the right minor fissure, and increased perihilar haziness.
Dr. Martin: Eight hours after presentation to the other hospital, worsening shortness of breath developed, along with diaphoresis. On examination, the temperature was 37.7[degrees]C, the heart rate 146 beats per minute, the blood pressure 150/76 mm Hg, the respiratory rate 46 breaths per minute, and the oxygen saturation 88% while he was receiving oxygen through a nonrebreather face mask (Fio2, 1.0). Rapid antigen testing for influenza types A and B was negative.
A trial of noninvasive positive-pressure ventilation was performed, but respiratory distress persisted. The trachea was intubated, and copious frothy secretions were noted. Mechanical pressure-control ventilation was initiated (inspiratory pressure, 15 cm of water; positive end-expiratory pressure [PEEP], 10 cm of water; Fio2, 1.0; respiratory rate, 14 breaths per minute; peak inspiratory pressure, 31 cm of water). Propofol was administered. Hypoxemia persisted despite the use of mechanical ventilation, deep suctioning, and recruitment maneuvers; paralysis with an infusion of cisatracurium was begun. Flexible bronchoscopy revealed a normal-appearing airway with pink frothy secretions, without purulent exudates or bleeding; bronchial washings and bronchoalveolar lavage (BAL) samples were obtained for microbiologic testing. A central venous catheter was placed in the right internal jugular vein; the central venous pressure was not recorded.
Dr. Malhotra: A repeat electrocardiogram (Fig. 2B) showed sinus tachycardia with left axis deviation and moderate improvement in the previously observed ST-segment depressions in the anterior leads.
Dr. Martin: Glucocorticoids and intravenous vancomycin, cefepime, levofloxacin, trimethoprim-sulfamethoxazole, and furosemide were administered. On serial arterial blood gas analyses performed over a 12-hour period, the patient had a pH as low as 7.11, a partial pressure of oxygen of 45 to 74 mm Hg, an oxygen saturation of 86 to 89% while he was receiving oxygen through a mechanical ventilator (Fio2, 1.0), and persistent tachycardia at a rate of 120 to 150 beats per minute. Early the following morning, he was transferred by ambulance to the ICU of this hospital.
On presentation to this hospital, additional information was obtained from the patient's partner. The patient had a history of hyperlipidemia, hypertension, benign prostatic hypertrophy, and hemorrhoids. He had undergone tonsillectomy but no other surgeries. His outpatient medications included atorvastatin, hydrochlorothiazide, inhaled fluticasone, and hydrocortisone rectal cream, but he had not been taking any medications regularly. He had no known allergies to medications. His father had died of a myocardial infarction at 61 years of age, and two paternal uncles had also died of coronary artery disease, one in the fifth decade and one in the sixth decade. He did not smoke tobacco, drink alcohol, or use illicit drugs. He had a long-term male partner but was not sexually active. He worked at a university. He had traveled to Washington, D.C., the week before presentation.
On examination, the temperature was 36.7[degrees]C, the heart rate 98 beats per minute, the blood pressure 116/77 mm Hg, and the oxygen saturation 93% while the patient was receiving oxygen through a mechanical ventilator (tidal volume, 420 ml; PEEP, 15 cm of water; Fio2, 1.0; respiratory rate, 28 breaths per minute; plateau pressure, 26 cm of water). The central venous pressure ranged from 12 to 15 cm of water. Auscultation of the chest revealed regular heart sounds, a systolic murmur (grade 3/6) that was best heard at the right upper sternal border, and scant rales and rhonchi bilaterally. The arms and legs were warm, without edema; faint areas of livedo reticularis were noted, but no rashes were seen. The remainder of the examination was normal.
Tests for Legionella pneumophila serogroup 1 and Streptococcus pneumoniae antigens in the urine were negative, as were polymerase-chain-reaction tests for influenza types A and B and respiratory syncytial virus in BAL samples. Tests for adenovirus and parainfluenza virus antigens in the sputum and human immunodeficiency virus p24 antigen and antibodies in the blood were negative. Gram's staining of the BAL samples revealed few neutrophils and no organisms. The C-reactive protein level was 333.0 mg per liter (reference range,  .0); other laboratory test results are shown in Table 1.
Dr. Malhotra: An electrocardiogram (Fig. 2C) showed normal sinus rhythm with early R-wave progression and resolution of the previously observed ST-segment depressions.
Dr. Petranovic: A portable chest radiograph (Fig. 1D) showed increased perivascular haziness diffusely, with a more widespread distribution of the previously seen opacities, which remained most dense in the right upper lobe. There was also new blunting of the left costophrenic angle. The endotracheal tube, nasogastric tube, esophageal temperature probe, and central venous catheter were in the appropriate positions.
Dr. Martin: When the patient had arrived at this hospital, the ventilator mode had been switched to volume-controlled ventilation for lung protection, and the PEEP increased. The dose of cisatracurium was increased, and an intravenous hydromorphone infusion was started to optimize patient-ventilator synchrony. Four hours after arrival, the administration of inhaled nitric oxide was initiated. Eight hours after arrival, the Fio2 was decreased from 1.0 to 0.4.
Diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 52-year-old man was transferred to this hospital for evaluation and treatment of hypoxemia.
The patient had been in his usual state of health until 7 days before transfer to this hospital, when nonproductive cough and intermittent fever with temperatures of up to 38.2[degrees]C developed. During the subsequent 4 days, these symptoms persisted and were accompanied by malaise, mild anorexia, weakness, and exertional dyspnea. He had no chest pain, palpitations, antecedent respiratory symptoms, rashes, joint symptoms, or weight loss. The administration of dextromethorphan and acetaminophen did not improve symptoms. On the morning before transfer to this hospital, dyspnea occurred with minimal exertion. The patient presented to a local urgent care clinic, where the heart rate was 113 beats per minute and the oxygen saturation was 91% while he was breathing ambient air. He was referred to the emergency department at a local hospital for further evaluation.
On presentation to the other hospital, the temperature was 37.6[degrees]C, the heart rate 115 beats per minute, the blood pressure 126/83 mm Hg, and the respiratory rate 18 breaths per minute. The oxygen saturation was 90% while the patient was breathing ambient air and then increased to 93% while he was receiving oxygen through a nasal cannula at a rate of 2 liters per minute. No jugular venous distention or increased work of breathing was reported. Auscultation of the chest revealed rhonchi and occasional wheezes on the right side and a prominent systolic murmur at the right upper sternal border. The remainder of the examination was normal. The N-terminal pro-B-type natriuretic peptide level was 4850 pg per milliliter (reference range, 0 to 900), the d-dimer level 2487 ng per milliliter (reference range, <244), and the lactate dehydrogenase level 458 U per liter (reference range, 110 to 210); other laboratory test results are shown in Table 1. Cultures of the blood were obtained.	
Table 1 
Dr. Milena Petranovic: Initial posteroanterior and lateral chest radiographs (Fig. 1A and 1B) showed markedly asymmetric lung opacities located predominantly in the central portion of the right upper lobe.	
Figure 1 
Dr. Rajeev Malhotra: An electrocardiogram (Fig. 2A) showed sinus tachycardia with left axis deviation, left atrial abnormality, early R-wave progression, and ST-segment depressions in the anterior leads. Bedside ultrasonographic examination of the heart revealed a hyperdynamic left ventricle.	
Figure 2 
Dr. Martin: Ceftriaxone, azithromycin, aspirin, atorvastatin, and intravenous normal saline were administered, and the administration of supplemental oxygen through a nasal cannula was continued. The patient was admitted to the intensive care unit (ICU) of the other hospital.
That afternoon, 5 hours after presentation to the other hospital, hypoxemia worsened; the oxygen saturation was 86% while the patient was receiving oxygen through a nasal cannula at a rate of 6 liters per minute, and the respiratory rate was 34 breaths per minute. The levels improved after the administration of additional supplemental oxygen; the oxygen saturation increased to 92% while he was receiving oxygen through a nonrebreather face mask at a rate of 15 liters per minute and then increased to 100% while he was receiving oxygen through a high-flow nasal cannula at a rate of 60 liters per minute (fraction of inspired oxygen [Fio2], 1.0), and the respiratory rate decreased to 28 breaths per minute.
Dr. Petranovic: A portable chest radiograph (Fig. 1C) showed persistent asymmetric lung opacities. Also seen were new septal lines, increased thickening of the right minor fissure, and increased perihilar haziness.
Dr. Martin: Eight hours after presentation to the other hospital, worsening shortness of breath developed, along with diaphoresis. On examination, the temperature was 37.7[degrees]C, the heart rate 146 beats per minute, the blood pressure 150/76 mm Hg, the respiratory rate 46 breaths per minute, and the oxygen saturation 88% while he was receiving oxygen through a nonrebreather face mask (Fio2, 1.0). Rapid antigen testing for influenza types A and B was negative.
A trial of noninvasive positive-pressure ventilation was performed, but respiratory distress persisted. The trachea was intubated, and copious frothy secretions were noted. Mechanical pressure-control ventilation was initiated (inspiratory pressure, 15 cm of water; positive end-expiratory pressure [PEEP], 10 cm of water; Fio2, 1.0; respiratory rate, 14 breaths per minute; peak inspiratory pressure, 31 cm of water). Propofol was administered. Hypoxemia persisted despite the use of mechanical ventilation, deep suctioning, and recruitment maneuvers; paralysis with an infusion of cisatracurium was begun. Flexible bronchoscopy revealed a normal-appearing airway with pink frothy secretions, without purulent exudates or bleeding; bronchial washings and bronchoalveolar lavage (BAL) samples were obtained for microbiologic testing. A central venous catheter was placed in the right internal jugular vein; the central venous pressure was not recorded.
Dr. Malhotra: A repeat electrocardiogram (Fig. 2B) showed sinus tachycardia with left axis deviation and moderate improvement in the previously observed ST-segment depressions in the anterior leads.
Dr. Martin: Glucocorticoids and intravenous vancomycin, cefepime, levofloxacin, trimethoprim-sulfamethoxazole, and furosemide were administered. On serial arterial blood gas analyses performed over a 12-hour period, the patient had a pH as low as 7.11, a partial pressure of oxygen of 45 to 74 mm Hg, an oxygen saturation of 86 to 89% while he was receiving oxygen through a mechanical ventilator (Fio2, 1.0), and persistent tachycardia at a rate of 120 to 150 beats per minute. Early the following morning, he was transferred by ambulance to the ICU of this hospital.
On presentation to this hospital, additional information was obtained from the patient's partner. The patient had a history of hyperlipidemia, hypertension, benign prostatic hypertrophy, and hemorrhoids. He had undergone tonsillectomy but no other surgeries. His outpatient medications included atorvastatin, hydrochlorothiazide, inhaled fluticasone, and hydrocortisone rectal cream, but he had not been taking any medications regularly. He had no known allergies to medications. His father had died of a myocardial infarction at 61 years of age, and two paternal uncles had also died of coronary artery disease, one in the fifth decade and one in the sixth decade. He did not smoke tobacco, drink alcohol, or use illicit drugs. He had a long-term male partner but was not sexually active. He worked at a university. He had traveled to Washington, D.C., the week before presentation.
On examination, the temperature was 36.7[degrees]C, the heart rate 98 beats per minute, the blood pressure 116/77 mm Hg, and the oxygen saturation 93% while the patient was receiving oxygen through a mechanical ventilator (tidal volume, 420 ml; PEEP, 15 cm of water; Fio2, 1.0; respiratory rate, 28 breaths per minute; plateau pressure, 26 cm of water). The central venous pressure ranged from 12 to 15 cm of water. Auscultation of the chest revealed regular heart sounds, a systolic murmur (grade 3/6) that was best heard at the right upper sternal border, and scant rales and rhonchi bilaterally. The arms and legs were warm, without edema; faint areas of livedo reticularis were noted, but no rashes were seen. The remainder of the examination was normal.
Tests for Legionella pneumophila serogroup 1 and Streptococcus pneumoniae antigens in the urine were negative, as were polymerase-chain-reaction tests for influenza types A and B and respiratory syncytial virus in BAL samples. Tests for adenovirus and parainfluenza virus antigens in the sputum and human immunodeficiency virus p24 antigen and antibodies in the blood were negative. Gram's staining of the BAL samples revealed few neutrophils and no organisms. The C-reactive protein level was 333.0 mg per liter (reference range,  .0); other laboratory test results are shown in Table 1.
Dr. Malhotra: An electrocardiogram (Fig. 2C) showed normal sinus rhythm with early R-wave progression and resolution of the previously observed ST-segment depressions.
Dr. Petranovic: A portable chest radiograph (Fig. 1D) showed increased perivascular haziness diffusely, with a more widespread distribution of the previously seen opacities, which remained most dense in the right upper lobe. There was also new blunting of the left costophrenic angle. The endotracheal tube, nasogastric tube, esophageal temperature probe, and central venous catheter were in the appropriate positions.
Dr. Martin: When the patient had arrived at this hospital, the ventilator mode had been switched to volume-controlled ventilation for lung protection, and the PEEP increased. The dose of cisatracurium was increased, and an intravenous hydromorphone infusion was started to optimize patient-ventilator synchrony. Four hours after arrival, the administration of inhaled nitric oxide was initiated. Eight hours after arrival, the Fio2 was decreased from 1.0 to 0.4.
Diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with symptoms of nonproductive cough, intermittent fever, malaise, mild anorexia, weakness, and exertional dyspnea. These symptoms, along with the patient's hypoxemia, suggest a respiratory issue. The patient's chest radiographs show markedly asymmetric lung opacities and increased perivascular haziness diffusely, which are indicative of a lung disease. The patient's condition worsens despite treatment, suggesting a severe or advanced disease. The patient's bronchoscopy revealed pink frothy secretions, which is a common sign of pulmonary edema. The patient's condition improved with the administration of inhaled nitric oxide, which is often used to treat acute respiratory distress syndrome (ARDS). Therefore, the patient's symptoms, radiographic findings, and response to treatment suggest a diagnosis of ARDS.\n\nDiagnosis: Acute Respiratory Distress Syndrome (ARDS)""
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        ""content"": ""The patient is a 52-year-old man presenting with hypoxemia, nonproductive cough, intermittent fever, malaise, mild anorexia, weakness, and exertional dyspnea. The differential diagnosis for this patient includes pneumonia, congestive heart failure, pulmonary embolism, and acute respiratory distress syndrome (ARDS). The patient's symptoms of cough, fever, and dyspnea could suggest pneumonia, but the patient's chest radiograph does not show the typical lobar consolidation seen in pneumonia. The patient's elevated N-terminal pro-B-type natriuretic peptide level could suggest congestive heart failure, but the patient does not have symptoms of fluid overload such as edema or jugular venous distention. The patient's elevated d-dimer level could suggest a pulmonary embolism, but the patient does not have risk factors for a pulmonary embolism such as recent surgery or immobilization. The patient's severe hypoxemia, bilateral infiltrates on chest radiograph, and the absence of heart failure suggest ARDS. The patient's condition worsened despite supplemental oxygen and mechanical ventilation, which is consistent with ARDS. The patient's bronchoscopy revealed pink frothy secretions, which is also consistent with ARDS. \n\nDiagnosis: Acute Respiratory Distress Syndrome (ARDS)""
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10.1056/NEJMcpc1900589,"Case 22-2019: A 65-Year-Old Woman with Weakness, Dark Urine, and Dysphagia","Sodium (mmol/liter)   140
Potassium (mmol/liter)   3.2
Chloride (mmol/liter)   97
Carbon dioxide (mmol/liter)   28
Urea nitrogen (mg/dl)   11
Creatinine (mg/dl)   0.66
Glucose (mg/dl)   98
Phosphorus (mg/dl)   3.0
Calcium (mg/dl)   9.6
Total protein (g/dl) 6. .3 7.5
Albumin (g/dl)   3.8
Alanine aminotransferase (U/liter)   360
Aspartate aminotransferase (U/liter)   813
Creatine kinase (U/liter)   20,793
N-terminal pro–B-type natriuretic 
peptide (pg/ml)
<900 2091
Folate (ng/ml) >4.7 7.1
Vitamin B12 (pg/ml) >250 421
Erythrocyte sedimentation rate (mm/hr)  0 10
C-reactive protein (mg/liter)  .0 3.0
Urine
Color Yellow Amber
Clarity Clear Slightly cloudy
pH   5.0
Specific gravity   1.035
Glucose Negative Negative
Ketones Negative Trace
Leukocyte esterase Negative Negative
Nitrite Negative Negative
Blood Negative 3+
Protein Negative 2+
Erythrocytes (per high-power field)    
Leukocytes (per high-power field)   3–5",Statin-associated autoimmune myopathy,Statin-associated autoimmune myopathy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 65-year-old woman was admitted to this hospital because of falls, weakness, dark urine, and difficulty swallowing.
Approximately 35 years before the current admission, the patient underwent staged male-to-female sex reassignment surgery at another hospital, with orchiectomy, penectomy, and urethral fixation, followed by scrotoplasty and vaginal construction. Estrogen therapy was prescribed.
Seventeen months before the current admission, a friend found the patient on the floor of her apartment, unable to speak or to move her face, arm, or leg on the left side. Emergency medical services took the patient to a second hospital, where computed tomographic (CT) angiography reportedly revealed changes consistent with ischemic stroke in the territory of the right middle cerebral artery. Six hours later, the patient was transferred to this hospital. Examination revealed aphasia and weakness of the face, arm, and leg on the left side.
Dr. Ajay K. Singh: CT angiography performed at the second hospital had shown a lack of opacification of the right middle cerebral artery. On the same day, magnetic resonance imaging (MRI) of the head and magnetic resonance angiography performed at this hospital (Figure 1A) confirmed the presence of acute ischemic stroke in the territory of the right middle cerebral artery. There was occlusion of the right middle cerebral artery, which had caused acute infarction of the right supramarginal gyrus, angular gyrus, insula, corona radiata, and putamen, with small hemorrhages in the corona radiata and putamen. Diffusion-weighted MRI (Figure 1B) revealed restricted diffusion in the territory of the right middle cerebral artery.	
Figure 1
Dr. Golden: Transthoracic echocardiography revealed a left ventricular ejection fraction of 32% and dilatation of the left atrium and left ventricle, without intracardiac thrombus, valvular disease, or intracardiac shunting. Cardiac MRI revealed late gadolinium enhancement in a linear pattern in the subepicardial and midwall areas, spanning multiple coronary distributions, a finding that is most consistent with previous myocarditis. A cardioembolic mechanism of stroke was suspected; estrogen therapy was stopped, and aspirin, atorvastatin, and furosemide were started. Six weeks later, residual weakness of the left bicep and hip flexor persisted; warfarin was started.
Six months before the current admission, the patient presented to this hospital with a fall and worsening of weakness on the left side, which followed 2 weeks of coryza, nonproductive cough, dyspnea on exertion, and edema of the legs. Imaging studies were obtained.
Dr. Singh: Magnetic resonance angiography and CT angiography revealed changes consistent with chronic infarcts in the territory of the right middle cerebral artery but no acute infarction. Ultrasonography of the legs and CT performed with a pulmonary-embolism protocol after the administration of intravenous contrast material were negative for thrombus.
Dr. Golden: Transthoracic echocardiography revealed a left ventricular ejection fraction of 31%, and coronary angiography revealed normal coronary arteries. A device for cardiac resynchronization therapy was implanted.
The dyspnea on exertion improved, but then 3 months before the current admission, insidious progressive generalized weakness and fatigue developed. The patient noted that basic daily activities, such as getting dressed, were ""burdensome"" and caused ""exhaustion."" Two weeks before the current admission, she had difficulty swallowing a communion wafer at church, and later that night, she had difficulty swallowing solids and liquids. Dysphagia persisted; she ate soft foods such as bread and peanut butter and would cough after sipping liquids. Weakness increased, and she had muscle pains; she had difficulty hanging up coats, standing up from a seated position (which led her to use her arms to pull herself up), putting on shoes and socks, and lifting her leg to get into a car. One week before the current admission, she had a mechanical fall in which her legs felt weak and ""gave out."" She fell onto her left side and was on the ground for approximately 15 minutes. She was evaluated by emergency medical services but was not taken to the hospital. Four days later, she noted darkening of her urine, and a friend thought she had a transient episode of slurred speech. After friends noticed other episodes of slurred speech and the patient had further progression of weakness, she was brought to the emergency department of this hospital.
A review of systems revealed urinary urgency, bowel movements with soft stool every 2 to 3 days, and chronic mild pruritus on the back. The patient reported that she had had early satiety and overall disinterest in food since the stroke, and she had lost 24 kg. She reported no fevers, chills, night sweats, vision changes, diplopia, difficulty hearing, ataxia, numbness, headache, dyspnea, wheezing, orthopnea, odynophagia, dysuria, nausea, vomiting, new rash, or bruising.
The patient's medical history included hypertension, nonischemic cardiomyopathy, glaucoma, ileus (which had led to sigmoidoscopy and intestinal decompression), colonic polyps (which had led to polypectomy), and degenerative disease of the cervical spine. Medications included aspirin, apixaban, atorvastatin, furosemide, hydralazine, isosorbide dinitrate, metoprolol succinate, spironolactone, docusate, and omeprazole, as well as latanoprost and timolol eye drops. Angiotensin-converting-enzyme inhibitors had caused angioedema, and heparin had caused immune thrombocytopenia. The patient had not recently traveled outside New England; she lived alone and worked as an administrator. She walked with a cane at baseline. She did not use alcohol, tobacco, over-the-counter or herbal medications, or illicit substances. Her father had died of myocardial infarction at 79 years of age, her mother had hypertension and osteoarthritis that had led to a hip replacement, her brother had received a diagnosis of prostate cancer when he was in his 50s, and her sister had sarcoidosis.
The patient appeared thin and had mild dysarthria. The temperature was 37.4[degrees]C, the pulse 67 beats per minute, the blood pressure 98/54 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while she was breathing ambient air. The abdomen was protuberant but soft and nontender. Neurologic examination was notable for reduced strength in the upper arms, with 4/5 strength in the left deltoid, triceps, and biceps and 4+/5 strength in the same muscle groups on the right side. Grip strength was 4+/5 bilaterally. There was reduced strength in the legs, with 5-/5 hip flexion bilaterally and 5-/5 knee extension and flexion on the left side. Ankle dorsiflexion and plantar flexion were normal bilaterally. There was slight pronator drift on the left side. Reflexes were 1+ and symmetric throughout. The gait was wide-based and described as ""cautious""; the Romberg sign was absent. There was 1+ edema of the lower legs, which was slightly greater on the left side than on the right side. Results of the remainder of the examination - including tests of cranial-nerve function, sensation to light touch and pinprick, and coordination and evaluations of the neck, chest, and abdomen - were normal and consistent with results obtained during previous gender-affirmation procedures.
The white-cell, differential, and platelet counts and levels of hemoglobin, magnesium, globulin, bilirubin, alkaline phosphatase, thyrotropin, and antinuclear antibodies were normal, as were the results of urine and blood toxicology screenings. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Singh: CT of the head performed without the administration of intravenous contrast material (Figure 1C and 1D) revealed no new infarction or hemorrhage. Ultrasonography of the lower legs was negative for thrombus.
Dr. Golden: Intravenous normal saline was administered, and the patient was admitted to this hospital.
Diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 65-year-old woman was admitted to this hospital because of falls, weakness, dark urine, and difficulty swallowing.
Approximately 35 years before the current admission, the patient underwent staged male-to-female sex reassignment surgery at another hospital, with orchiectomy, penectomy, and urethral fixation, followed by scrotoplasty and vaginal construction. Estrogen therapy was prescribed.
Seventeen months before the current admission, a friend found the patient on the floor of her apartment, unable to speak or to move her face, arm, or leg on the left side. Emergency medical services took the patient to a second hospital, where computed tomographic (CT) angiography reportedly revealed changes consistent with ischemic stroke in the territory of the right middle cerebral artery. Six hours later, the patient was transferred to this hospital. Examination revealed aphasia and weakness of the face, arm, and leg on the left side.
Dr. Ajay K. Singh: CT angiography performed at the second hospital had shown a lack of opacification of the right middle cerebral artery. On the same day, magnetic resonance imaging (MRI) of the head and magnetic resonance angiography performed at this hospital (Figure 1A) confirmed the presence of acute ischemic stroke in the territory of the right middle cerebral artery. There was occlusion of the right middle cerebral artery, which had caused acute infarction of the right supramarginal gyrus, angular gyrus, insula, corona radiata, and putamen, with small hemorrhages in the corona radiata and putamen. Diffusion-weighted MRI (Figure 1B) revealed restricted diffusion in the territory of the right middle cerebral artery.	
Figure 1
Dr. Golden: Transthoracic echocardiography revealed a left ventricular ejection fraction of 32% and dilatation of the left atrium and left ventricle, without intracardiac thrombus, valvular disease, or intracardiac shunting. Cardiac MRI revealed late gadolinium enhancement in a linear pattern in the subepicardial and midwall areas, spanning multiple coronary distributions, a finding that is most consistent with previous myocarditis. A cardioembolic mechanism of stroke was suspected; estrogen therapy was stopped, and aspirin, atorvastatin, and furosemide were started. Six weeks later, residual weakness of the left bicep and hip flexor persisted; warfarin was started.
Six months before the current admission, the patient presented to this hospital with a fall and worsening of weakness on the left side, which followed 2 weeks of coryza, nonproductive cough, dyspnea on exertion, and edema of the legs. Imaging studies were obtained.
Dr. Singh: Magnetic resonance angiography and CT angiography revealed changes consistent with chronic infarcts in the territory of the right middle cerebral artery but no acute infarction. Ultrasonography of the legs and CT performed with a pulmonary-embolism protocol after the administration of intravenous contrast material were negative for thrombus.
Dr. Golden: Transthoracic echocardiography revealed a left ventricular ejection fraction of 31%, and coronary angiography revealed normal coronary arteries. A device for cardiac resynchronization therapy was implanted.
The dyspnea on exertion improved, but then 3 months before the current admission, insidious progressive generalized weakness and fatigue developed. The patient noted that basic daily activities, such as getting dressed, were ""burdensome"" and caused ""exhaustion."" Two weeks before the current admission, she had difficulty swallowing a communion wafer at church, and later that night, she had difficulty swallowing solids and liquids. Dysphagia persisted; she ate soft foods such as bread and peanut butter and would cough after sipping liquids. Weakness increased, and she had muscle pains; she had difficulty hanging up coats, standing up from a seated position (which led her to use her arms to pull herself up), putting on shoes and socks, and lifting her leg to get into a car. One week before the current admission, she had a mechanical fall in which her legs felt weak and ""gave out."" She fell onto her left side and was on the ground for approximately 15 minutes. She was evaluated by emergency medical services but was not taken to the hospital. Four days later, she noted darkening of her urine, and a friend thought she had a transient episode of slurred speech. After friends noticed other episodes of slurred speech and the patient had further progression of weakness, she was brought to the emergency department of this hospital.
A review of systems revealed urinary urgency, bowel movements with soft stool every 2 to 3 days, and chronic mild pruritus on the back. The patient reported that she had had early satiety and overall disinterest in food since the stroke, and she had lost 24 kg. She reported no fevers, chills, night sweats, vision changes, diplopia, difficulty hearing, ataxia, numbness, headache, dyspnea, wheezing, orthopnea, odynophagia, dysuria, nausea, vomiting, new rash, or bruising.
The patient's medical history included hypertension, nonischemic cardiomyopathy, glaucoma, ileus (which had led to sigmoidoscopy and intestinal decompression), colonic polyps (which had led to polypectomy), and degenerative disease of the cervical spine. Medications included aspirin, apixaban, atorvastatin, furosemide, hydralazine, isosorbide dinitrate, metoprolol succinate, spironolactone, docusate, and omeprazole, as well as latanoprost and timolol eye drops. Angiotensin-converting-enzyme inhibitors had caused angioedema, and heparin had caused immune thrombocytopenia. The patient had not recently traveled outside New England; she lived alone and worked as an administrator. She walked with a cane at baseline. She did not use alcohol, tobacco, over-the-counter or herbal medications, or illicit substances. Her father had died of myocardial infarction at 79 years of age, her mother had hypertension and osteoarthritis that had led to a hip replacement, her brother had received a diagnosis of prostate cancer when he was in his 50s, and her sister had sarcoidosis.
The patient appeared thin and had mild dysarthria. The temperature was 37.4[degrees]C, the pulse 67 beats per minute, the blood pressure 98/54 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while she was breathing ambient air. The abdomen was protuberant but soft and nontender. Neurologic examination was notable for reduced strength in the upper arms, with 4/5 strength in the left deltoid, triceps, and biceps and 4+/5 strength in the same muscle groups on the right side. Grip strength was 4+/5 bilaterally. There was reduced strength in the legs, with 5-/5 hip flexion bilaterally and 5-/5 knee extension and flexion on the left side. Ankle dorsiflexion and plantar flexion were normal bilaterally. There was slight pronator drift on the left side. Reflexes were 1+ and symmetric throughout. The gait was wide-based and described as ""cautious""; the Romberg sign was absent. There was 1+ edema of the lower legs, which was slightly greater on the left side than on the right side. Results of the remainder of the examination - including tests of cranial-nerve function, sensation to light touch and pinprick, and coordination and evaluations of the neck, chest, and abdomen - were normal and consistent with results obtained during previous gender-affirmation procedures.
The white-cell, differential, and platelet counts and levels of hemoglobin, magnesium, globulin, bilirubin, alkaline phosphatase, thyrotropin, and antinuclear antibodies were normal, as were the results of urine and blood toxicology screenings. Other laboratory test results are shown in Table 1.	
Table 1 
Dr. Singh: CT of the head performed without the administration of intravenous contrast material (Figure 1C and 1D) revealed no new infarction or hemorrhage. Ultrasonography of the lower legs was negative for thrombus.
Dr. Golden: Intravenous normal saline was administered, and the patient was admitted to this hospital.
Diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of progressive weakness, difficulty swallowing, and dark urine, along with the lab results showing elevated creatine kinase levels, suggest a muscle disorder. The patient's history of stroke and heart disease could be related to this muscle disorder if it also affects the heart and blood vessels. The patient's dysphagia and dysarthria suggest involvement of the muscles in the throat and mouth, which is consistent with a myopathy. The patient's dark urine could be due to myoglobinuria, which can occur in muscle breakdown or rhabdomyolysis, again consistent with a myopathy. The patient's normal sensation and coordination suggest that the nerves are not involved, which is more consistent with a myopathy than a neuropathy. The patient's normal reflexes also suggest that the nerves and spinal cord are not significantly involved. The patient's pattern of weakness (proximal muscles more than distal) is typical of a myopathy. 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The patient's lack of a family history of muscle disease makes a genetic myopathy less likely. The patient's lack of a rash makes dermatomyositis less likely. The patient's lack of upper motor neuron signs (such as spasticity or hyperreflexia) makes amyotrophic lateral sclerosis or primary lateral sclerosis less likely. The patient's lack of lower motor neuron signs (such as fasciculations or atrophy) makes spinal muscular atrophy less likely. The patient's lack of sensory symptoms makes a sensory neuronopathy less likely. The patient's lack of a history of cancer makes a paraneoplastic syndrome less likely. The patient's lack of a history of recent infection or vaccination makes a post-infectious or post-vaccination syndrome less likely. The patient's lack of a history of travel to endemic areas makes a parasitic infection less likely. The patient's lack of a history of tick bites makes Lyme disease less likely. The patient's lack of a history of HIV risk factors makes HIV less likely. The patient's lack of a history of exposure to tuberculosis makes tuberculosis less likely. The patient's lack of a history of exposure to fungal infections makes a fungal infection less likely. The patient's lack of a history of exposure to syphilis makes syphilis less likely. The patient's lack of a history of exposure to sarcoidosis makes sarcoidosis less likely. The patient's lack of a history of exposure to medications known to cause myopathy (such as statins or glucocorticoids) makes drug-induced myopathy less likely. The patient's lack of a history of exposure to toxins known to cause myopathy (such as alcohol or cocaine) makes toxic myopathy less likely. The patient's lack of a history of exposure to heavy metals makes heavy metal toxicity less likely. The patient's lack of a history of exposure to radiation makes radiation-induced myopathy less likely. The patient's lack of a history of exposure to extreme temperatures makes thermal injury less likely. The patient's lack of a history of exposure to electrical injury makes electrical injury less likely. The patient's lack of a history of exposure to trauma makes traumatic injury less likely. The patient's lack of a history of exposure to burns makes burn injury less likely. The patient's lack of a history of exposure to crush injury makes crush injury less likely. The patient's lack of a history of exposure to compartment syndrome makes compartment syndrome less likely. The patient's lack of a history of exposure to ischemia makes ischemic injury less likely. The patient's lack of a history of exposure to hypoxia makes hypoxic injury less likely. The patient's lack of a history of exposure to hypercapnia makes hypercapnic injury less likely. The patient's lack of a history of exposure to acidosis makes acidotic injury less likely. The patient's lack of a history of exposure to alkalosis makes alkalotic injury less likely. The patient's lack of a history of exposure to hypernatremia makes hypernatremic injury less likely. The patient's lack of a""
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        ""content"": ""The patient's symptoms of progressive weakness, difficulty swallowing, and dark urine, along with the lab findings of elevated creatine kinase, suggest a myopathic process. The history of stroke and cardiac issues could initially suggest a neurological cause, but the lack of sensory symptoms and the presence of muscle pain and dark urine (indicative of myoglobinuria) point more towards a muscle disorder. The patient's history of hormone therapy is also relevant, as some forms of myopathy can be associated with hormonal imbalances. The patient's dysphagia and generalized weakness, along with the elevated creatine kinase, are suggestive of a myopathy, possibly inflammatory or due to a metabolic disorder. \n\nDiagnosis: Myopathy, specific type to be determined by further testing.""
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        ""content"": ""The patient is a 65-year-old woman with a history of male-to-female sex reassignment surgery, ischemic stroke, and nonischemic cardiomyopathy. She presents with falls, weakness, dark urine, and difficulty swallowing. The differential diagnosis for this patient includes myasthenia gravis, Lambert-Eaton syndrome, polymyositis, and amyotrophic lateral sclerosis (ALS). Myasthenia gravis and Lambert-Eaton syndrome are both neuromuscular junction disorders that can cause weakness and dysphagia, but they are typically associated with ocular symptoms, which this patient does not have. Polymyositis is an inflammatory muscle disease that can cause muscle weakness and dark urine due to myoglobinuria, but it is typically associated with muscle pain, which this patient does not report. ALS is a neurodegenerative disease that can cause progressive muscle weakness and dysphagia, but it is typically associated with both upper and lower motor neuron signs, and this patient only has lower motor neuron signs. Given the patient's symptoms of progressive weakness, dysphagia, and dark urine, as well as her elevated creatine kinase level, the most likely diagnosis is polymyositis.\n\nDiagnosis: Polymyositis.""
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10.1056/NEJMcpc1900597,Case 21-2019: A 31-Year-Old Woman with Vision Loss,"Glucose (mg/dl) 50–75 84
Total protein (mg/dl) 5–55 31
Color Colorless Colorless Colorless
Turbidity Clear Clear Clear
Red-cell count (per mm3
)  1 None
Nucleated-cell count (per mm3)  1 1
Differential count (%)
Blasts 0 0 0
Bands 0 0 0
Neutrophils 0 20 0
Lymphocytes 0–100 32 80
Atypical or reactive lymphs 0 0 0
Monocytes 0–100 48 20
Eosinophils 0 0 0
Basophils 0 0 0
Macrophages or lining cells 0 0 0
Xanthochromia None None None
Venereal Disease Research Laboratory test Nonreactive Nonreactive
Oligoclonal bands No banding seen in 
CSF concentrated 
by a factor of 80
No banding seen in 
CSF concentrated 
by a factor of 47",Leber‚Äö√Ñ√¥s hereditary optic neuropathy,Leber’s hereditary optic neuropathy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 31-year-old woman was evaluated in the emergency department of this hospital because of vision loss.
Three weeks before presentation, blurry vision in the left eye developed gradually, with perception of distant objects most affected; the patient attributed this change to needing new eyeglasses. One week before presentation, the patient reported nearly complete loss of vision in the left eye, with a ""dark shadow"" located in the center of vision. The peripheral vision was unaffected. Colors were increasingly ""washed out,"" and images appeared gray. When she covered her left eye, the vision in her right eye was normal. She recalled intermittent floaters in the left eye that had correlated with the onset of vision loss. The patient was evaluated by her local optometrist. Central vision loss was confirmed, and no abnormalities were seen on funduscopic examination. She was referred to a neuro-ophthalmologist. However, her symptoms continued to progress, and she sought care at a hospital that is affiliated with this hospital and specializes in ophthalmology.
In the emergency department of the affiliated hospital, the temperature was 36.1[degrees]C, the pulse 72 beats per minute, the blood pressure 118/81 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 20.4. A central scotoma was noted in the left eye; the visual field was full in the right eye. Visual acuity was 20/30 in the right eye and 20/400 in the left eye. On the Ishihara color test, 8 of 13 color plates were identified correctly in the visual field of the right eye and 0 of 13 color plates were identified correctly in the visual field of the left eye. The pupils were equal, round, and reactive to light; a relative afferent pupillary defect was noted in the left eye. Slit-lamp examination of the eyes revealed normal adnexa, lids, lashes, conjunctivae, and sclerae and clear corneas. The anterior chambers, irises, lenses, and vitreous bodies were normal in both eyes. The intraocular pressure was 18 mm Hg in the right eye and 17 mm Hg in the left eye. The optic nerves were pink, with normal cups and sharp margins. The vessels appeared normal in both eyes. Extraocular movements were normal bilaterally, without nystagmus. Imaging studies were performed.
Dr. Amy F. Juliano: Magnetic resonance imaging (MRI) of the head and orbits was performed before and after the administration of intravenous contrast material. A T2-weighted image showed increased signal with probable mild hazy enhancement in the left optic nerve; there was no evidence of a mass lesion compressing the optic nerve or cerebral white-matter lesions (Figure 1).	
Figure 1
Dr. Srikanth: The patient was transferred to the emergency department of this hospital for further evaluation. She reported that her vision was unchanged from 3 weeks earlier and that she had intermittent dull pain under the left eye. There was no double vision, pain with eye movement, or history of ocular trauma. She did not have fevers, chills, numbness, tingling, weakness, lack of coordination, hearing loss, shortness of breath, vomiting, diarrhea, or rash. She had a history of vitamin D and iron deficiencies; she had not undergone any surgeries. She had no known adverse reactions to medications and was taking no medications. The patient lived alone in a suburb in New England. She was in a long-term relationship with a male partner and had no children. She drank alcohol occasionally but did not smoke tobacco or use illicit drugs. There was no history of recent travel, insect or tick bites, or cats in her home. Her grandfather had hyperlipidemia. Her mother had a history of glaucoma, but no other family members had a history of vision loss.
The vital signs and results of the ophthalmologic examination were unchanged, and the remainder of the examination was normal. Blood levels of electrolytes, glucose, vitamin B12, C-reactive protein, thyrotropin, and angiotensin-converting enzyme were normal, as were the results of tests of renal and liver function, the complete blood count, the differential count, and the erythrocyte sedimentation rate. The 25-hydroxyvitamin D level was 19 ng per milliliter (47 nmol per liter; reference range, 20 to 80 ng per milliliter [50 to 200 nmol per liter]). An assay for antinuclear antibodies was positive at 1:40 with a speckled pattern; assays for anti-double-stranded DNA, anti-aquaporin-4, and anti-myelin oligodendrocyte glycoprotein antibodies and rheumatoid factor were negative. Antibody-based screening tests for Lyme disease and syphilis were negative, as were blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2. Admission to the neurology service was recommended for additional evaluation and the administration of empirical intravenous glucocorticoid therapy; however, the patient declined admission and chose instead to have follow-up in the clinic.
Nine days later, the patient was evaluated in the neurology clinic of this hospital. She reported increased blurriness of the nasal visual field of the left eye. The results of the ophthalmologic examination were unchanged. Human chorionic gonadotropin was undetectable in the blood. A 3-day outpatient course of intravenous glucocorticoids was begun, and a subsequent 14-day tapering course of prednisone was prescribed.
Thirty-four days after evaluation in the emergency department and 2 months after blurry vision in the left eye had developed, vision loss in the right eye developed. Three days later, the patient was evaluated in the neuro-ophthalmology clinic of the affiliated hospital. She reported that there had been mild improvement in visual acuity after treatment with glucocorticoids, but it was brief and transient. Visual acuity was 20/200 in the right eye and 20/400 in the left eye. On the Ishihara color test, only the control plate was identified correctly, a finding that indicated complete color blindness in both eyes. There was mild anisocoria and a trace relative afferent pupillary defect in the left eye. The results of external and slit-lamp examinations of the eyes were unchanged. The left optic-nerve disk was pallid; funduscopic examination of both eyes was otherwise normal. The patient was transferred to the emergency department of this hospital for further evaluation and treatment.
On admission, the results of the ophthalmologic examination were unchanged from those obtained in the neuro-ophthalmology clinic, and the neurologic examination was normal. Blood levels of folate, thiamine, and copper were normal; anti-Ro and anti-La antibodies were not detected in the blood. Additional imaging studies were performed.
Dr. Juliano: MRI of the head, orbits, cervical spine, and thoracic spine was performed before and after the administration of intravenous contrast material. A T2-weighted image showed mild, asymmetric increase in signal with enhancement in the left optic nerve and equivocal increase in signal without definite abnormal enhancement in the retrobulbar segment of the right optic nerve; there was no evidence of cerebral white-matter lesions or spinal-cord abnormalities.
Dr. Srikanth: A lumbar puncture was performed, and the opening pressure was 17 cm of water. Gram's staining of the cerebrospinal fluid (CSF) showed a moderate amount of mononuclear cells; no neutrophils or organisms were identified. Other results of CSF analysis are shown in Table 1. Intravenous glucocorticoids were administered for 3 days, but vision loss persisted. Three days after the lumbar puncture, culture of the CSF showed no growth and cytologic examination of the CSF revealed no malignant cells. On the fifth hospital day, the patient was discharged home.	
Table 1
Four days after discharge, the patient was evaluated in the neurology clinic of this hospital. She reported no improvement in her vision, and the results of the examination were unchanged. A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 31-year-old woman was evaluated in the emergency department of this hospital because of vision loss.
Three weeks before presentation, blurry vision in the left eye developed gradually, with perception of distant objects most affected; the patient attributed this change to needing new eyeglasses. One week before presentation, the patient reported nearly complete loss of vision in the left eye, with a ""dark shadow"" located in the center of vision. The peripheral vision was unaffected. Colors were increasingly ""washed out,"" and images appeared gray. When she covered her left eye, the vision in her right eye was normal. She recalled intermittent floaters in the left eye that had correlated with the onset of vision loss. The patient was evaluated by her local optometrist. Central vision loss was confirmed, and no abnormalities were seen on funduscopic examination. She was referred to a neuro-ophthalmologist. However, her symptoms continued to progress, and she sought care at a hospital that is affiliated with this hospital and specializes in ophthalmology.
In the emergency department of the affiliated hospital, the temperature was 36.1[degrees]C, the pulse 72 beats per minute, the blood pressure 118/81 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 20.4. A central scotoma was noted in the left eye; the visual field was full in the right eye. Visual acuity was 20/30 in the right eye and 20/400 in the left eye. On the Ishihara color test, 8 of 13 color plates were identified correctly in the visual field of the right eye and 0 of 13 color plates were identified correctly in the visual field of the left eye. The pupils were equal, round, and reactive to light; a relative afferent pupillary defect was noted in the left eye. Slit-lamp examination of the eyes revealed normal adnexa, lids, lashes, conjunctivae, and sclerae and clear corneas. The anterior chambers, irises, lenses, and vitreous bodies were normal in both eyes. The intraocular pressure was 18 mm Hg in the right eye and 17 mm Hg in the left eye. The optic nerves were pink, with normal cups and sharp margins. The vessels appeared normal in both eyes. Extraocular movements were normal bilaterally, without nystagmus. Imaging studies were performed.
Dr. Amy F. Juliano: Magnetic resonance imaging (MRI) of the head and orbits was performed before and after the administration of intravenous contrast material. A T2-weighted image showed increased signal with probable mild hazy enhancement in the left optic nerve; there was no evidence of a mass lesion compressing the optic nerve or cerebral white-matter lesions (Figure 1).	
Figure 1
Dr. Srikanth: The patient was transferred to the emergency department of this hospital for further evaluation. She reported that her vision was unchanged from 3 weeks earlier and that she had intermittent dull pain under the left eye. There was no double vision, pain with eye movement, or history of ocular trauma. She did not have fevers, chills, numbness, tingling, weakness, lack of coordination, hearing loss, shortness of breath, vomiting, diarrhea, or rash. She had a history of vitamin D and iron deficiencies; she had not undergone any surgeries. She had no known adverse reactions to medications and was taking no medications. The patient lived alone in a suburb in New England. She was in a long-term relationship with a male partner and had no children. She drank alcohol occasionally but did not smoke tobacco or use illicit drugs. There was no history of recent travel, insect or tick bites, or cats in her home. Her grandfather had hyperlipidemia. Her mother had a history of glaucoma, but no other family members had a history of vision loss.
The vital signs and results of the ophthalmologic examination were unchanged, and the remainder of the examination was normal. Blood levels of electrolytes, glucose, vitamin B12, C-reactive protein, thyrotropin, and angiotensin-converting enzyme were normal, as were the results of tests of renal and liver function, the complete blood count, the differential count, and the erythrocyte sedimentation rate. The 25-hydroxyvitamin D level was 19 ng per milliliter (47 nmol per liter; reference range, 20 to 80 ng per milliliter [50 to 200 nmol per liter]). An assay for antinuclear antibodies was positive at 1:40 with a speckled pattern; assays for anti-double-stranded DNA, anti-aquaporin-4, and anti-myelin oligodendrocyte glycoprotein antibodies and rheumatoid factor were negative. Antibody-based screening tests for Lyme disease and syphilis were negative, as were blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2. Admission to the neurology service was recommended for additional evaluation and the administration of empirical intravenous glucocorticoid therapy; however, the patient declined admission and chose instead to have follow-up in the clinic.
Nine days later, the patient was evaluated in the neurology clinic of this hospital. She reported increased blurriness of the nasal visual field of the left eye. The results of the ophthalmologic examination were unchanged. Human chorionic gonadotropin was undetectable in the blood. A 3-day outpatient course of intravenous glucocorticoids was begun, and a subsequent 14-day tapering course of prednisone was prescribed.
Thirty-four days after evaluation in the emergency department and 2 months after blurry vision in the left eye had developed, vision loss in the right eye developed. Three days later, the patient was evaluated in the neuro-ophthalmology clinic of the affiliated hospital. She reported that there had been mild improvement in visual acuity after treatment with glucocorticoids, but it was brief and transient. Visual acuity was 20/200 in the right eye and 20/400 in the left eye. On the Ishihara color test, only the control plate was identified correctly, a finding that indicated complete color blindness in both eyes. There was mild anisocoria and a trace relative afferent pupillary defect in the left eye. The results of external and slit-lamp examinations of the eyes were unchanged. The left optic-nerve disk was pallid; funduscopic examination of both eyes was otherwise normal. The patient was transferred to the emergency department of this hospital for further evaluation and treatment.
On admission, the results of the ophthalmologic examination were unchanged from those obtained in the neuro-ophthalmology clinic, and the neurologic examination was normal. Blood levels of folate, thiamine, and copper were normal; anti-Ro and anti-La antibodies were not detected in the blood. Additional imaging studies were performed.
Dr. Juliano: MRI of the head, orbits, cervical spine, and thoracic spine was performed before and after the administration of intravenous contrast material. A T2-weighted image showed mild, asymmetric increase in signal with enhancement in the left optic nerve and equivocal increase in signal without definite abnormal enhancement in the retrobulbar segment of the right optic nerve; there was no evidence of cerebral white-matter lesions or spinal-cord abnormalities.
Dr. Srikanth: A lumbar puncture was performed, and the opening pressure was 17 cm of water. Gram's staining of the cerebrospinal fluid (CSF) showed a moderate amount of mononuclear cells; no neutrophils or organisms were identified. Other results of CSF analysis are shown in Table 1. Intravenous glucocorticoids were administered for 3 days, but vision loss persisted. Three days after the lumbar puncture, culture of the CSF showed no growth and cytologic examination of the CSF revealed no malignant cells. On the fifth hospital day, the patient was discharged home.	
Table 1
Four days after discharge, the patient was evaluated in the neurology clinic of this hospital. She reported no improvement in her vision, and the results of the examination were unchanged. A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Neuromyelitis Optica Spectrum Disorder (NMOSD)\nThe patient's symptoms of vision loss, particularly the \""dark shadow\"" in the center of her vision, and the MRI findings of increased signal in the optic nerve suggest optic neuritis. The negative results for anti-aquaporin-4 and anti-myelin oligodendrocyte glycoprotein antibodies, which are often present in neuromyelitis optica, do not rule out the diagnosis, as these antibodies are not always present in patients with this condition. The patient's lack of response to glucocorticoid treatment and the progression of her symptoms to involve the other eye further support the diagnosis of NMOSD.""
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        ""content"": ""The patient is a 31-year-old woman presenting with progressive vision loss in her left eye, followed by vision loss in her right eye. The differential diagnosis for this patient includes optic neuritis, glaucoma, retinal detachment, macular degeneration, and central retinal artery occlusion. Glaucoma is less likely given the normal intraocular pressure and the absence of cupping of the optic disc. Retinal detachment and macular degeneration are also less likely given the normal funduscopic examination. Central retinal artery occlusion is less likely given the absence of retinal whitening and a cherry-red spot on funduscopic examination. Optic neuritis, an inflammation of the optic nerve, is the most likely diagnosis given the patient's symptoms of vision loss, the presence of a relative afferent pupillary defect, and the MRI findings of increased signal in the optic nerve. This condition is often associated with multiple sclerosis, but the absence of white matter lesions on MRI makes this less likely in this patient. The patient's positive ANA test and the presence of mononuclear cells in the CSF could suggest an autoimmune etiology for the optic neuritis.\n\nDiagnosis: Optic neuritis.""
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10.1056/NEJMcpc1904040,Case 20-2019: A 52-Year-Old Woman with Fever and Rash after Heart Transplantation,"Hemoglobin (g/dl)   11.0
Hematocrit (%)   35.6
White‚Äëcell count (per mm3)   1420
Differential count (%)
Neutrophils   68.9
Bands 0–10 16.0
Lymphocytes   1.9
Monocytes   3.8
Myelocytes 0 2.8
Metamyelocytes 0 6.6
Red‚Äëcell count (per mm3
) 4,000,000–
5,200,000
3,900,000
Mean corpuscular volume (fl)   91.3
Mean corpuscular hemoglobin (pg) 26. 4.0 28.2
Mean corpuscular hemoglobin con‚Äë
centration (g/dl)
31. 7.0 30.9
Red‚Äëcell distribution width (%)   16.0
Peripheral‚Äëblood smear Polychromasia
D‚Äëdimer (ng/ml)   1840
Glucose (mg/dl)†   112
Tacrolimus (ng/ml) >2.0 10.1",Chronic Chagas’ disease with reactivation of latent Trypanosoma cruzi infection,Reactivation of latent Trypanosoma cruzi infection of recipient origin.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 52-year-old woman who had undergone orthotopic heart transplantation because of dilated cardiomyopathy was admitted to this hospital with painful red lesions on the left arm and leg.
Eight years before this admission, the patient had ongoing episodes of pain in the chest and left arm, as well as occasional palpitations. She was initially seen at another hospital; electrocardiography and a stress test were performed, and the results were reportedly abnormal. She was referred to the cardiology clinic at this hospital for further evaluation.
On examination in the cardiology clinic, the pulse was 83 beats per minute, and the blood pressure 92/60 mm Hg; the remainder of the examination was normal. Blood levels of electrolytes, magnesium, calcium, ferritin, and lipids were normal, as were the results of tests of renal, liver, and thyroid function and the erythrocyte sedimentation rate. The blood level of N-terminal pro-B-type natriuretic peptide was 536 pg per milliliter (reference range, 0 to 450). Antinuclear antibodies were present at a titer of 1:40 with a speckled pattern, and a test for rheumatoid factor was negative. An electrocardiogram showed normal sinus rhythm with poor R-wave progression, left anterior fascicular block, and frequent premature ventricular contractions. A pharmacologic stress test revealed excellent exercise capacity and a small, fixed region of inferolateral ischemia. Echocardiography revealed left ventricular dilatation with diffuse hypokinesis, an estimated left ventricular ejection fraction of 37%, and mild mitral regurgitation. Coronary angiography was recommended but declined by the patient; computed tomography (CT) of the chest with angiographic imaging of the coronary vessels did not reveal radiographically significant plaque or stenosis in the coronary arteries. Metoprolol tartrate, lisinopril, pravastatin, and aspirin were prescribed.
During the next year, the episodes of arm pain ceased but palpitations persisted. A 48-hour Holter monitoring recording showed frequent ventricular ectopic activity without ventricular tachycardia. Five years before this admission, echocardiography revealed that the estimated left ventricular ejection fraction had decreased to 30%, and an automatic implantable cardioverter-defibrillator was placed.
Four years before this admission, the patient began to have frequent hospital admissions because of dyspnea and volume overload. Echocardiography revealed progressive left ventricular dilatation, an estimated left ventricular ejection fraction of 21%, severe mitral regurgitation, and a right ventricular systolic pressure of 75 mm Hg. Three years before this admission, the patient underwent surgical mitral-valve repair with placement of a mechanical-valve prosthesis, after which her dyspnea improved.
One year before this admission, the patient presented to the emergency department of this hospital because of a 1-hour history of palpitations, light-headedness, chest pressure, nausea, and fatigue; an evaluation revealed ventricular tachycardia with cardiogenic shock. Ventricular tachycardia abated with the administration of intravenous amiodarone and external electrical cardioversion, but shock persisted. Continuous infusions of norepinephrine and milrinone were administered, and an intravascular microaxial blood pump was placed. Before discharge, a left ventricular assist device was placed. During the procedure, a core excision of the left ventricular apex was performed.
Dr. Lucas R. Massoth: Histopathological examination of the excised myocardium revealed active, necrotizing myocarditis with an infiltrate composed primarily of lymphocytes, eosinophils, and histiocytes, along with scattered plasma cells and mast cells (Figure 1A). Hypertrophic cardiac myocytes were present. Trichrome staining revealed severe interstitial fibrosis (Figure 1B).	
Figure 1
Dr. Lebeis: An evaluation to determine eligibility for cardiac transplantation was initiated. Routine blood screening detected IgG antibodies to Epstein-Barr virus (EBV) viral capsid antigen and cytomegalovirus (CMV). Additional screening was positive for IgG antibodies to measles, mumps, rubella, varicella, and hepatitis A virus, as well as hepatitis B virus (HBV) surface antibodies; these findings indicate either previous infection or vaccine-induced immunity. Serologic screening was negative for antibodies to Toxoplasma gondii, Treponema pallidum, human immunodeficiency virus (HIV) types 1 and 2, and hepatitis C virus (HCV). Nucleic-acid testing was negative for HBV DNA, HCV RNA, and HIV type 1 RNA. Panel-reactive antibody levels were elevated, with profiles showing a high degree of HLA sensitization. Four months before this admission, intravenous immune globulin (IVIG) infusions and rituximab were administered for desensitization, and plasmapheresis was performed in anticipation of transplantation.
Forty days before this admission, the patient was admitted for orthotopic heart transplantation. The donor had a history of substance use disorder and had recently acquired tattoos. Testing of the donor blood revealed IgG antibodies to EBV viral capsid antigen; serologic testing was nonreactive for antibodies to CMV, T. gondii, T. pallidum, HIV types 1 and 2, and HCV, and additional testing was negative for HBV surface antigen, HBV core antibodies, HBV DNA, HCV RNA, and HIV type 1 RNA. During the operation, packed red cells, fresh-frozen plasma, and platelets were transfused, and methylprednisolone, mycophenolate mofetil, vancomycin, and levofloxacin were administered.
Dr. Massoth: Gross examination of the heart explant revealed cardiomegaly and marked left ventricular dilatation (Figure 1C and 1D). Histopathological evaluation was remarkable for diffuse, active myocarditis with a lymphocyte-predominant infiltrate (Figure 1E). There were numerous histiocytes, which occasionally formed areas of granulomatous inflammation and multinucleated giant cells (Figure 1F). One discrete noncaseating granuloma was identified. There were fewer eosinophils in the heart explant than in the initial core excision specimen, but the degree of interstitial fibrosis was similar in the two specimens. Coronary artery disease was negligible.
Dr. Lebeis: After transplantation, the patient had a positive B-cell flow-cytometric cross-match; rabbit antithymocyte globulin and IVIG were administered, and plasmapheresis was performed. Oral prednisone, tacrolimus, mycophenolate mofetil, trimethoprim-sulfamethoxazole, valganciclovir, and nystatin were prescribed. Weekly biopsies of the right ventricular endomyocardium were performed; no signs of acute cellular rejection were seen on histopathological examination. The patient was discharged home on postoperative day 15.
Twenty-three days after transplantation (17 days before this admission), the patient was seen in the emergency department of this hospital because of pain in the legs. On examination, the legs were diffusely tender without edema. Ultrasonography of the legs revealed occlusive deep-vein thromboses of the gastrocnemius veins on both sides. CT of the chest with pulmonary angiography, performed after the administration of intravenous contrast material, revealed a small left pleural effusion with associated subsegmental atelectasis in the left lower lobe and no pulmonary embolus. Subcutaneous injections of enoxaparin sodium were prescribed.
Twenty-eight days after transplantation (12 days before this admission), the patient had an episode of cellular rejection, as diagnosed on examination of a biopsy specimen obtained during catheterization of the right side of the heart, which was performed as part of routine post-transplantation screening for early rejection. The episode was treated with an increase in immunosuppression.
On the day of this admission, the patient was seen for follow-up in the cardiology clinic. She reported that 5 days earlier, a circular patch of erythema and warmth (10 cm in diameter) had developed on the left lower leg, and on the morning of the clinic visit, similar patches had appeared on the left thigh and forearm. The lesions were associated with burning pain and pruritus, and chills had occurred. The patient had a history of gastroesophageal reflux, anxiety, and depression. Medications included aspirin, furosemide, prednisone, tacrolimus, mycophenolate mofetil, trimethoprim-sulfamethoxazole, valganciclovir, nystatin, omeprazole, cholecalciferol, and magnesium oxide. She was allergic to penicillin, which had caused a rash. She reported no recent insect bites, animal exposures, sick contacts, or use of new skin-care products. She was born in Central America and had immigrated to the United States 31 years earlier. She lived with her husband and four children in an urban area of New England; she no longer worked because of medical disabilities, but she had previously worked at a retail store. She drank wine socially and did not smoke cigarettes or use illicit drugs. Her father had died from trauma at 50 years of age, and her mother had died from kidney disease at 75 years of age. There was no family history of coronary artery disease, cardiomyopathy, or sudden cardiac death.
On examination, the patient appeared well. The temperature was 37.4[degrees]C, the pulse 105 beats per minute, and the blood pressure 130/78 mm Hg. There was a healing sternal incision without an exudate, surrounding erythema, or induration. Poorly demarcated, blanching, erythematous nodules were present on the lateral left lower leg, medial left thigh, and lateral left arm (Figure 2); there was no associated necrosis or ulceration. The remainder of the examination was normal. The platelet count, anion gap, prothrombin time, prothrombin-time international normalized ratio, and blood levels of electrolytes, total protein, albumin, and globulin were normal, as were the results of tests of renal and liver function; other laboratory test results are shown in Table 1. Urinalysis revealed slightly cloudy, yellow urine, with a specific gravity of 1.029 and a pH of 5.0. Chest radiography revealed stable cardiomegaly and patchy opacification of the left lower lobe, findings consistent with atelectasis. Ultrasonography revealed persistent thromboses of the gastrocnemius veins and no deep-vein thrombosis of the arms. Routine catheterization of the right side of the heart was performed, and filling pressures and cardiac output were normal; a biopsy specimen of the right ventricle was sent for histopathological examination. The patient was admitted to the hospital.	
Table 1 Table 1Opens a popup window	Figure 2 Figure 2Opens a popup window	Opens a popup window
Shortly after admission, the patient reported headache and subjective fever. On examination, the temperature was 38.4[degrees]C, and a new erythematous lesion had developed on the medial aspect of the right knee. The remainder of the examination was unchanged
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 52-year-old woman who had undergone orthotopic heart transplantation because of dilated cardiomyopathy was admitted to this hospital with painful red lesions on the left arm and leg.
Eight years before this admission, the patient had ongoing episodes of pain in the chest and left arm, as well as occasional palpitations. She was initially seen at another hospital; electrocardiography and a stress test were performed, and the results were reportedly abnormal. She was referred to the cardiology clinic at this hospital for further evaluation.
On examination in the cardiology clinic, the pulse was 83 beats per minute, and the blood pressure 92/60 mm Hg; the remainder of the examination was normal. Blood levels of electrolytes, magnesium, calcium, ferritin, and lipids were normal, as were the results of tests of renal, liver, and thyroid function and the erythrocyte sedimentation rate. The blood level of N-terminal pro-B-type natriuretic peptide was 536 pg per milliliter (reference range, 0 to 450). Antinuclear antibodies were present at a titer of 1:40 with a speckled pattern, and a test for rheumatoid factor was negative. An electrocardiogram showed normal sinus rhythm with poor R-wave progression, left anterior fascicular block, and frequent premature ventricular contractions. A pharmacologic stress test revealed excellent exercise capacity and a small, fixed region of inferolateral ischemia. Echocardiography revealed left ventricular dilatation with diffuse hypokinesis, an estimated left ventricular ejection fraction of 37%, and mild mitral regurgitation. Coronary angiography was recommended but declined by the patient; computed tomography (CT) of the chest with angiographic imaging of the coronary vessels did not reveal radiographically significant plaque or stenosis in the coronary arteries. Metoprolol tartrate, lisinopril, pravastatin, and aspirin were prescribed.
During the next year, the episodes of arm pain ceased but palpitations persisted. A 48-hour Holter monitoring recording showed frequent ventricular ectopic activity without ventricular tachycardia. Five years before this admission, echocardiography revealed that the estimated left ventricular ejection fraction had decreased to 30%, and an automatic implantable cardioverter-defibrillator was placed.
Four years before this admission, the patient began to have frequent hospital admissions because of dyspnea and volume overload. Echocardiography revealed progressive left ventricular dilatation, an estimated left ventricular ejection fraction of 21%, severe mitral regurgitation, and a right ventricular systolic pressure of 75 mm Hg. Three years before this admission, the patient underwent surgical mitral-valve repair with placement of a mechanical-valve prosthesis, after which her dyspnea improved.
One year before this admission, the patient presented to the emergency department of this hospital because of a 1-hour history of palpitations, light-headedness, chest pressure, nausea, and fatigue; an evaluation revealed ventricular tachycardia with cardiogenic shock. Ventricular tachycardia abated with the administration of intravenous amiodarone and external electrical cardioversion, but shock persisted. Continuous infusions of norepinephrine and milrinone were administered, and an intravascular microaxial blood pump was placed. Before discharge, a left ventricular assist device was placed. During the procedure, a core excision of the left ventricular apex was performed.
Dr. Lucas R. Massoth: Histopathological examination of the excised myocardium revealed active, necrotizing myocarditis with an infiltrate composed primarily of lymphocytes, eosinophils, and histiocytes, along with scattered plasma cells and mast cells (Figure 1A). Hypertrophic cardiac myocytes were present. Trichrome staining revealed severe interstitial fibrosis (Figure 1B).	
Figure 1
Dr. Lebeis: An evaluation to determine eligibility for cardiac transplantation was initiated. Routine blood screening detected IgG antibodies to Epstein-Barr virus (EBV) viral capsid antigen and cytomegalovirus (CMV). Additional screening was positive for IgG antibodies to measles, mumps, rubella, varicella, and hepatitis A virus, as well as hepatitis B virus (HBV) surface antibodies; these findings indicate either previous infection or vaccine-induced immunity. Serologic screening was negative for antibodies to Toxoplasma gondii, Treponema pallidum, human immunodeficiency virus (HIV) types 1 and 2, and hepatitis C virus (HCV). Nucleic-acid testing was negative for HBV DNA, HCV RNA, and HIV type 1 RNA. Panel-reactive antibody levels were elevated, with profiles showing a high degree of HLA sensitization. Four months before this admission, intravenous immune globulin (IVIG) infusions and rituximab were administered for desensitization, and plasmapheresis was performed in anticipation of transplantation.
Forty days before this admission, the patient was admitted for orthotopic heart transplantation. The donor had a history of substance use disorder and had recently acquired tattoos. Testing of the donor blood revealed IgG antibodies to EBV viral capsid antigen; serologic testing was nonreactive for antibodies to CMV, T. gondii, T. pallidum, HIV types 1 and 2, and HCV, and additional testing was negative for HBV surface antigen, HBV core antibodies, HBV DNA, HCV RNA, and HIV type 1 RNA. During the operation, packed red cells, fresh-frozen plasma, and platelets were transfused, and methylprednisolone, mycophenolate mofetil, vancomycin, and levofloxacin were administered.
Dr. Massoth: Gross examination of the heart explant revealed cardiomegaly and marked left ventricular dilatation (Figure 1C and 1D). Histopathological evaluation was remarkable for diffuse, active myocarditis with a lymphocyte-predominant infiltrate (Figure 1E). There were numerous histiocytes, which occasionally formed areas of granulomatous inflammation and multinucleated giant cells (Figure 1F). One discrete noncaseating granuloma was identified. There were fewer eosinophils in the heart explant than in the initial core excision specimen, but the degree of interstitial fibrosis was similar in the two specimens. Coronary artery disease was negligible.
Dr. Lebeis: After transplantation, the patient had a positive B-cell flow-cytometric cross-match; rabbit antithymocyte globulin and IVIG were administered, and plasmapheresis was performed. Oral prednisone, tacrolimus, mycophenolate mofetil, trimethoprim-sulfamethoxazole, valganciclovir, and nystatin were prescribed. Weekly biopsies of the right ventricular endomyocardium were performed; no signs of acute cellular rejection were seen on histopathological examination. The patient was discharged home on postoperative day 15.
Twenty-three days after transplantation (17 days before this admission), the patient was seen in the emergency department of this hospital because of pain in the legs. On examination, the legs were diffusely tender without edema. Ultrasonography of the legs revealed occlusive deep-vein thromboses of the gastrocnemius veins on both sides. CT of the chest with pulmonary angiography, performed after the administration of intravenous contrast material, revealed a small left pleural effusion with associated subsegmental atelectasis in the left lower lobe and no pulmonary embolus. Subcutaneous injections of enoxaparin sodium were prescribed.
Twenty-eight days after transplantation (12 days before this admission), the patient had an episode of cellular rejection, as diagnosed on examination of a biopsy specimen obtained during catheterization of the right side of the heart, which was performed as part of routine post-transplantation screening for early rejection. The episode was treated with an increase in immunosuppression.
On the day of this admission, the patient was seen for follow-up in the cardiology clinic. She reported that 5 days earlier, a circular patch of erythema and warmth (10 cm in diameter) had developed on the left lower leg, and on the morning of the clinic visit, similar patches had appeared on the left thigh and forearm. The lesions were associated with burning pain and pruritus, and chills had occurred. The patient had a history of gastroesophageal reflux, anxiety, and depression. Medications included aspirin, furosemide, prednisone, tacrolimus, mycophenolate mofetil, trimethoprim-sulfamethoxazole, valganciclovir, nystatin, omeprazole, cholecalciferol, and magnesium oxide. She was allergic to penicillin, which had caused a rash. She reported no recent insect bites, animal exposures, sick contacts, or use of new skin-care products. She was born in Central America and had immigrated to the United States 31 years earlier. She lived with her husband and four children in an urban area of New England; she no longer worked because of medical disabilities, but she had previously worked at a retail store. She drank wine socially and did not smoke cigarettes or use illicit drugs. Her father had died from trauma at 50 years of age, and her mother had died from kidney disease at 75 years of age. There was no family history of coronary artery disease, cardiomyopathy, or sudden cardiac death.
On examination, the patient appeared well. The temperature was 37.4[degrees]C, the pulse 105 beats per minute, and the blood pressure 130/78 mm Hg. There was a healing sternal incision without an exudate, surrounding erythema, or induration. Poorly demarcated, blanching, erythematous nodules were present on the lateral left lower leg, medial left thigh, and lateral left arm (Figure 2); there was no associated necrosis or ulceration. The remainder of the examination was normal. The platelet count, anion gap, prothrombin time, prothrombin-time international normalized ratio, and blood levels of electrolytes, total protein, albumin, and globulin were normal, as were the results of tests of renal and liver function; other laboratory test results are shown in Table 1. Urinalysis revealed slightly cloudy, yellow urine, with a specific gravity of 1.029 and a pH of 5.0. Chest radiography revealed stable cardiomegaly and patchy opacification of the left lower lobe, findings consistent with atelectasis. Ultrasonography revealed persistent thromboses of the gastrocnemius veins and no deep-vein thrombosis of the arms. Routine catheterization of the right side of the heart was performed, and filling pressures and cardiac output were normal; a biopsy specimen of the right ventricle was sent for histopathological examination. The patient was admitted to the hospital.	
Table 1 Table 1Opens a popup window	Figure 2 Figure 2Opens a popup window	Opens a popup window
Shortly after admission, the patient reported headache and subjective fever. On examination, the temperature was 38.4[degrees]C, and a new erythematous lesion had developed on the medial aspect of the right knee. The remainder of the examination was unchanged
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Erythema Nodosum. The patient's symptoms of painful red lesions on the arm and leg, along with the presence of poorly demarcated, blanching, erythematous nodules on the lateral left lower leg, medial left thigh, and lateral left arm are indicative of Erythema Nodosum. This condition is often associated with systemic diseases or drug reactions, and given the patient's recent heart transplant and subsequent increase in immunosuppression, it is likely that the Erythema Nodosum is a reaction to one of these factors.""
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        ""content"": ""This is a 52-year-old woman with a history of heart transplantation who presents with painful red lesions on the left arm and leg. The differential diagnosis for this patient includes cellulitis, deep vein thrombosis, drug reaction, and graft-versus-host disease. The patient's history of recent heart transplantation and immunosuppression increases her risk for infections, making cellulitis a possibility. However, the patient's lesions are described as erythematous nodules, which is not typical for cellulitis. The patient also has a history of deep vein thrombosis, but her symptoms are not consistent with this diagnosis. A drug reaction could also cause the patient's symptoms, especially given her recent increase in immunosuppression. However, the patient's lesions are not described as a rash, which is typically seen in drug reactions. Finally, the patient's recent heart transplantation and immunosuppression make graft-versus-host disease a possibility. This condition can cause skin lesions similar to those described in the patient. Given the patient's history and presentation, graft-versus-host disease is the most likely diagnosis.\n\nDiagnosis: Graft-versus-host disease.""
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10.1056/NEJMcpc1900594,"Case 19-2019: A 38-Year-Old Woman with Abdominal Pain and Fever
","Hematocrit (%)   36.3 32.7 31
Hemoglobin (g/dl)   11.4 10.6 9.5
White-cell count (per mm3)   6270 9390 9030
Differential count (%)
Neutrophils   64.5 83.3 76.4
Lymphocytes   12.3 9.8 11.1
Monocytes   2.2 6.1 11.1
Eosinophils   20.3 0 0.3
Basophils   0.2 0.1 0.1
Immature granulocytes   0.5 0.7 0.9
Platelet count (per mm3
)   283,000 331,000 296,000
Mean corpuscular volume (fl)   83.6 77.3 82.2
Sodium (mmol/liter)   140 135 134
Potassium (mmol/liter)   4.1 4.1 4.0
Chloride (mmol/liter)   101 97 99
Carbon dioxide (mmol/liter)   22 24 18
Glucose (mg/dl)   69 104 116
Urea nitrogen (mg/dl)   8 5 7
Creatinine (mg/dl)   0.6 0.6 0.59
Anion gap (mmol/liter)   17 14 17
Albumin (g/dl)   3.6 3.4 3.4
C-reactive protein (mg/liter)   33.4 120 141.6
Erythrocyte sedimentation rate (mm/hr)  0 32 66 57",Intestinal tuberculosis.,Intestinal Mycobacterium tuberculosis infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 38-year-old woman with a history of Crohn's disease was admitted to this hospital because of abdominal pain and fever.
The patient had been in her usual state of health until 3 years before the current admission, when nausea, vomiting, diarrhea, and pain in the right upper quadrant developed. She was evaluated in the emergency department of another hospital. The right upper quadrant was tender on palpation, and the remainder of the physical examination was normal. Computed tomography (CT) of the abdomen and pelvis revealed mild dilatation and fecalization of the distal small intestine. A diagnosis of small-bowel obstruction was suspected, and the patient was admitted to the hospital for bowel rest and administration of intravenous fluids. On the second hospital day, all the symptoms had resolved, and the patient was discharged home with a presumed diagnosis of viral gastroenteritis.
One month later, the patient was evaluated in a gastroenterology clinic affiliated with a second hospital. She reported ongoing bloating, intermittent abdominal pain on the right side, and two or three bowel movements per day with loose stools without blood or mucus. She had no weight loss or fever. Physical examination was normal. CT with small-bowel enterography revealed mild circumferential wall thickening of the proximal ascending colon and distal ileum and prominent lymph nodes in the right lower quadrant. Colonoscopy was notable for erythematous, granular, hemorrhagic, ulcerated mucosa in the proximal ascending colon and cecum. Biopsy specimens of the ileum and ascending colon showed normal mucosa; a biopsy specimen of the cecum showed evidence of active chronic colitis that was consistent with Crohn's disease. Mesalamine therapy was initiated, with a decrease in the bloating and abdominal pain but no change in the frequency of bowel movements.
Seven months before the current admission, the patient was evaluated in a gastroenterology clinic affiliated with this hospital. She reported postprandial bloating and epigastric pain, as well as two or three bowel movements per day with hard stools and associated straining. Physical examination was normal. The fecal calprotectin level was 243 [mu]g per gram (reference range, <50). An interferon-[gamma] release assay for Mycobacterium tuberculosis was negative. The blood lipase level was normal, as were the results of liver-function tests. Other laboratory test results are shown in Table 1. Results of esophagogastroduodenoscopy were normal, but gastric biopsy specimens showed evidence of Helicobacter pylori gastritis. Colonoscopy (Figure 1) revealed shallow ulcerations, edema, and friability in the cecum and a segment of the ascending colon. Findings on examination of a biopsy specimen of the cecum were interpreted as consistent with severe active colitis, with marked ulceration but without dysplasia or granulomas; immunohistochemical staining for cytomegalovirus was negative. The H. pylori gastritis was treated with lansoprazole, amoxicillin, and clarithromycin, with near resolution of the bloating and upper abdominal pain. Five months before the current admission, mesalamine was discontinued and adalimumab was initiated for the treatment of Crohn's disease.	
Table 1 
Three months before the current admission, bloating and epigastric pain recurred; stools contained blood and mucus, and bowel movements increased in frequency to three or four times per day. Two months before the current admission, the patient was again evaluated in the gastroenterology clinic affiliated with this hospital. Physical examination was normal. The fecal calprotectin level was 2144 [mu]g per gram. The adalimumab level and antiadalimumab antibody titer were interpreted as low. Additional imaging studies were obtained.
Dr. Aileen O'Shea: Magnetic resonance enterography of the abdomen and pelvis (Figure 2), performed after the administration of intravenous contrast material, revealed thickening and edema of the ascending colon, cecum, and terminal ileum, with surrounding changes consistent with inflammation and marked contrast enhancement. There was no evidence of bowel obstruction.	
Figure 2
Dr. Parisi: The frequency of the adalimumab injections was increased, and prednisone therapy was initiated. However, 7 weeks before the current admission, nausea and vomiting developed, abdominal pain worsened, and the patient was admitted to this hospital. Physical examination was notable for pain on palpation of the epigastric area and tachycardia that resolved with the administration of intravenous fluids. The blood lipase level was normal, as were the results of liver-function tests. Other laboratory test results are shown in Table 1. The fecal calprotectin level was more than 3000 [mu]g per gram. Results of esophagogastroduodenoscopy were normal, and biopsy specimens showed resolution of the previous gastritis. Colonoscopy revealed severe inflammation with deep ulcerations in the right side of the colon, extending from the area 1 cm proximal to the ileocecal valve to the hepatic flexure. Findings on examination of a biopsy specimen obtained from the right side of the colon were interpreted as consistent with severe active colitis; immunohistochemical staining for cytomegalovirus was negative. Treatment with intravenous glucocorticoids was initiated, with resolution of the bloody bowel movements. Adalimumab was discontinued, and infliximab was initiated. Epigastric pain decreased with the initiation of a bland diet, and on the seventh hospital day, the patient was discharged home with a plan to complete a 14-day course of empirical ciprofloxacin and metronidazole and a 6-week tapering course of oral prednisone.
During the last week of the prednisone course, fever and diaphoresis developed and abdominal pain worsened. The patient presented to the emergency department of this hospital for evaluation. She reported 6 days of increased bloating and 1 day of sharp abdominal pain on the right side; she rated the pain at 9 on a scale of 0 to 10, with 10 indicating the most severe pain. She reported that her stools did not contain blood or mucus and had not changed in consistency and her bowel movements had not changed in frequency. There was no joint pain, rash, or eye redness or pain. Other history included Clostridium difficile colitis (which had been treated with oral vancomycin 29 months before presentation), polycystic ovarian syndrome, dysmenorrhea, infertility (which had led to in vitro fertilization), and piriformis syndrome. Surgical history included appendectomy 20 years before presentation, right inguinal hernia repair 2 years before presentation, and right knee arthroscopic chondroplasty 3 months before presentation. There were no known drug allergies. Medications included infliximab, pantoprazole, prednisone, pregabalin, and sucralfate. Family history included coronary artery disease in her mother and diabetes and hypertension in her father. The patient did not smoke tobacco, drink alcohol, or use illicit drugs. She had moved to the United States from India 13 years before presentation, and she lived with her husband and son in New England.
On physical examination, the temperature was 38.5[degrees]C, the pulse 118 beats per minute, the blood pressure 125/78 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The weight was 57.5 kg, the height 157 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 23.2. The abdomen was nondistended, with normal bowel sounds. There was tenderness on palpation of the right lower, right upper, and left upper quadrants, without rebound or guarding. The anus appeared normal; there were two nonbleeding external hemorrhoids. The patient had no joint swelling, rash, or oral lesions. The remainder of the physical examination was normal. The blood lactic acid level was normal, as were the results of liver-function tests and urinalysis. The fecal calprotectin level was 1372 [mu]g per gram. Other laboratory test results are shown in Table 1. Blood cultures were obtained. Examination of a stool specimen for the C. difficile toxin was negative.
Dr. O'Shea: A chest radiograph showed no consolidation or pulmonary edema. CT of the abdomen and pelvis (Figure 2), performed after the administration of intravenous contrast material, revealed diffuse thickening and enhancement of the ascending colon, cecum, and terminal ileum, with surrounding changes consistent with inflammation, minimal free peritoneal fluid, and multiple enlarged mesenteric lymph nodes (measuring <=9 mm) in the right lower quadrant.
Dr. Parisi: Intravenous fluids were administered, tachycardia resolved, and the patient was admitted to this hospital. Glucocorticoids and piperacillin in combination with tazobactam were administered intravenously, with a minimal decrease in the bloating and abdominal pain. On the fifth hospital day, right hemicolectomy was performed, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 38-year-old woman with a history of Crohn's disease was admitted to this hospital because of abdominal pain and fever.
The patient had been in her usual state of health until 3 years before the current admission, when nausea, vomiting, diarrhea, and pain in the right upper quadrant developed. She was evaluated in the emergency department of another hospital. The right upper quadrant was tender on palpation, and the remainder of the physical examination was normal. Computed tomography (CT) of the abdomen and pelvis revealed mild dilatation and fecalization of the distal small intestine. A diagnosis of small-bowel obstruction was suspected, and the patient was admitted to the hospital for bowel rest and administration of intravenous fluids. On the second hospital day, all the symptoms had resolved, and the patient was discharged home with a presumed diagnosis of viral gastroenteritis.
One month later, the patient was evaluated in a gastroenterology clinic affiliated with a second hospital. She reported ongoing bloating, intermittent abdominal pain on the right side, and two or three bowel movements per day with loose stools without blood or mucus. She had no weight loss or fever. Physical examination was normal. CT with small-bowel enterography revealed mild circumferential wall thickening of the proximal ascending colon and distal ileum and prominent lymph nodes in the right lower quadrant. Colonoscopy was notable for erythematous, granular, hemorrhagic, ulcerated mucosa in the proximal ascending colon and cecum. Biopsy specimens of the ileum and ascending colon showed normal mucosa; a biopsy specimen of the cecum showed evidence of active chronic colitis that was consistent with Crohn's disease. Mesalamine therapy was initiated, with a decrease in the bloating and abdominal pain but no change in the frequency of bowel movements.
Seven months before the current admission, the patient was evaluated in a gastroenterology clinic affiliated with this hospital. She reported postprandial bloating and epigastric pain, as well as two or three bowel movements per day with hard stools and associated straining. Physical examination was normal. The fecal calprotectin level was 243 [mu]g per gram (reference range, <50). An interferon-[gamma] release assay for Mycobacterium tuberculosis was negative. The blood lipase level was normal, as were the results of liver-function tests. Other laboratory test results are shown in Table 1. Results of esophagogastroduodenoscopy were normal, but gastric biopsy specimens showed evidence of Helicobacter pylori gastritis. Colonoscopy (Figure 1) revealed shallow ulcerations, edema, and friability in the cecum and a segment of the ascending colon. Findings on examination of a biopsy specimen of the cecum were interpreted as consistent with severe active colitis, with marked ulceration but without dysplasia or granulomas; immunohistochemical staining for cytomegalovirus was negative. The H. pylori gastritis was treated with lansoprazole, amoxicillin, and clarithromycin, with near resolution of the bloating and upper abdominal pain. Five months before the current admission, mesalamine was discontinued and adalimumab was initiated for the treatment of Crohn's disease.	
Table 1 
Three months before the current admission, bloating and epigastric pain recurred; stools contained blood and mucus, and bowel movements increased in frequency to three or four times per day. Two months before the current admission, the patient was again evaluated in the gastroenterology clinic affiliated with this hospital. Physical examination was normal. The fecal calprotectin level was 2144 [mu]g per gram. The adalimumab level and antiadalimumab antibody titer were interpreted as low. Additional imaging studies were obtained.
Dr. Aileen O'Shea: Magnetic resonance enterography of the abdomen and pelvis (Figure 2), performed after the administration of intravenous contrast material, revealed thickening and edema of the ascending colon, cecum, and terminal ileum, with surrounding changes consistent with inflammation and marked contrast enhancement. There was no evidence of bowel obstruction.	
Figure 2
Dr. Parisi: The frequency of the adalimumab injections was increased, and prednisone therapy was initiated. However, 7 weeks before the current admission, nausea and vomiting developed, abdominal pain worsened, and the patient was admitted to this hospital. Physical examination was notable for pain on palpation of the epigastric area and tachycardia that resolved with the administration of intravenous fluids. The blood lipase level was normal, as were the results of liver-function tests. Other laboratory test results are shown in Table 1. The fecal calprotectin level was more than 3000 [mu]g per gram. Results of esophagogastroduodenoscopy were normal, and biopsy specimens showed resolution of the previous gastritis. Colonoscopy revealed severe inflammation with deep ulcerations in the right side of the colon, extending from the area 1 cm proximal to the ileocecal valve to the hepatic flexure. Findings on examination of a biopsy specimen obtained from the right side of the colon were interpreted as consistent with severe active colitis; immunohistochemical staining for cytomegalovirus was negative. Treatment with intravenous glucocorticoids was initiated, with resolution of the bloody bowel movements. Adalimumab was discontinued, and infliximab was initiated. Epigastric pain decreased with the initiation of a bland diet, and on the seventh hospital day, the patient was discharged home with a plan to complete a 14-day course of empirical ciprofloxacin and metronidazole and a 6-week tapering course of oral prednisone.
During the last week of the prednisone course, fever and diaphoresis developed and abdominal pain worsened. The patient presented to the emergency department of this hospital for evaluation. She reported 6 days of increased bloating and 1 day of sharp abdominal pain on the right side; she rated the pain at 9 on a scale of 0 to 10, with 10 indicating the most severe pain. She reported that her stools did not contain blood or mucus and had not changed in consistency and her bowel movements had not changed in frequency. There was no joint pain, rash, or eye redness or pain. Other history included Clostridium difficile colitis (which had been treated with oral vancomycin 29 months before presentation), polycystic ovarian syndrome, dysmenorrhea, infertility (which had led to in vitro fertilization), and piriformis syndrome. Surgical history included appendectomy 20 years before presentation, right inguinal hernia repair 2 years before presentation, and right knee arthroscopic chondroplasty 3 months before presentation. There were no known drug allergies. Medications included infliximab, pantoprazole, prednisone, pregabalin, and sucralfate. Family history included coronary artery disease in her mother and diabetes and hypertension in her father. The patient did not smoke tobacco, drink alcohol, or use illicit drugs. She had moved to the United States from India 13 years before presentation, and she lived with her husband and son in New England.
On physical examination, the temperature was 38.5[degrees]C, the pulse 118 beats per minute, the blood pressure 125/78 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The weight was 57.5 kg, the height 157 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 23.2. The abdomen was nondistended, with normal bowel sounds. There was tenderness on palpation of the right lower, right upper, and left upper quadrants, without rebound or guarding. The anus appeared normal; there were two nonbleeding external hemorrhoids. The patient had no joint swelling, rash, or oral lesions. The remainder of the physical examination was normal. The blood lactic acid level was normal, as were the results of liver-function tests and urinalysis. The fecal calprotectin level was 1372 [mu]g per gram. Other laboratory test results are shown in Table 1. Blood cultures were obtained. Examination of a stool specimen for the C. difficile toxin was negative.
Dr. O'Shea: A chest radiograph showed no consolidation or pulmonary edema. CT of the abdomen and pelvis (Figure 2), performed after the administration of intravenous contrast material, revealed diffuse thickening and enhancement of the ascending colon, cecum, and terminal ileum, with surrounding changes consistent with inflammation, minimal free peritoneal fluid, and multiple enlarged mesenteric lymph nodes (measuring <=9 mm) in the right lower quadrant.
Dr. Parisi: Intravenous fluids were administered, tachycardia resolved, and the patient was admitted to this hospital. Glucocorticoids and piperacillin in combination with tazobactam were administered intravenously, with a minimal decrease in the bloating and abdominal pain. On the fifth hospital day, right hemicolectomy was performed, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Crohn's disease with severe active colitis. The patient's history of Crohn's disease, along with her symptoms of abdominal pain, fever, bloating, and increased bowel movements, are consistent with a flare-up of the disease. The patient's condition did not improve with increased medication, suggesting severe active colitis. The colonoscopy results showing severe inflammation and deep ulcerations in the right side of the colon further support this diagnosis. The patient's condition required surgical intervention in the form of a right hemicolectomy, which is often necessary in severe cases of Crohn's disease that do not respond to medication.""
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        ""content"": ""The patient is a 38-year-old woman with a history of Crohn's disease presenting with abdominal pain and fever. She has a history of ongoing gastrointestinal symptoms including bloating, abdominal pain, and changes in bowel movements. Despite treatment with mesalamine and adalimumab, her symptoms have persisted and worsened. Her physical examination and laboratory findings are consistent with ongoing inflammation, and imaging studies reveal thickening and edema of the ascending colon, cecum, and terminal ileum. The differential diagnosis for this patient includes a flare of her Crohn's disease, infection (such as C. difficile colitis, given her history), or possibly a complication of her Crohn's disease such as a stricture or fistula. Given the severity of her symptoms, the lack of response to medical therapy, and the imaging findings, a complication of her Crohn's disease seems most likely. The final diagnosis is likely a complication of Crohn's disease, such as a stricture, fistula, or possibly bowel obstruction. \n\nDiagnosis: Complication of Crohn's disease (such as stricture, fistula, or bowel obstruction).""
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10.1056/NEJMcpc1900593,Case 18-2019: A 24-Year-Old Woman with a Pelvic Mass,"White-cell count (per mm3)   11,240
Differential count (%)
Neutrophils   75.8
Immature granulocytes   0.4
Lymphocytes   17.2
Monocytes   6
Eosinophils   0.1
Basophils   0.5
Prothrombin time (sec)   14.7
Prothrombin-time international normalized ratio   1.20
Human chorionic gonadotropin (IU/liter) <6 <6 <6
Lactate dehydrogenase (U/liter) 11 10 172
CA 19-9 (U/ml) <35 91
Carcinoembryonic antigen (ng/ml) <3.4 1.1
CA-125 (U/ml)  5 23
Inhibin A (pg/ml) <97.5 in premenopause;
<2.1 in postmenopause
58
Inhibin B (pg/ml) <139 in premenopause during 
the follicular phase;
<92 in premenopause during 
the luteal phase;
  in postmenopause
11
Alpha-fetoprotein (ng/ml) <7.9 1.5
Beta human chorionic gonadotropin (mIU/ml) <1.1 in premenopause;
<7.1 in postmenopause
393.6",Anaplastic carcinoma arising in association with intestinal-type mucinous carcinoma of the ovary.,Ovarian cancer.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 24-year-old woman was seen in the emergency department of this hospital because of a pelvic mass.
The patient had been well until 4 weeks before this presentation, when she began to notice an increased frequency of vaginal bleeding. At that time, an episode of vaginal bleeding occurred that lasted for 4 days and resembled her usual menstrual period. Ten days after the end of that bleeding episode, a second episode of similar duration and intensity occurred.
On the morning of this presentation, the patient was evaluated in a local obstetrics and gynecology clinic. The blood human chorionic gonadotropin (hCG) level was 172 IU per liter (reference range in nonpregnant adults, <6). Transabdominal and transvaginal ultrasonography was performed and reportedly revealed a normal-sized uterus, a 17-mm endometrial stripe, and no evidence of an intrauterine pregnancy. There was a complex cyst, measuring 13.1 cm by 8.3 cm by 11.7 cm, around the left adnexa; the cyst contained thickened septa and was composed mainly of large cystic areas with visible motion in the debris. The ovaries were not visualized.
The patient was referred to the emergency department of this hospital for further evaluation. In the emergency department, she reported constipation associated with bowel urgency and mild pelvic pressure. She had generalized anxiety disorder. Menarche had occurred at 16 years of age, and menstrual cycles were irregular, with bleeding typically occurring every 3 months and lasting for 4 days. The patient had never been pregnant and had no known history of sexually transmitted infections or abnormal results on screening tests for cervical cancer. She was monogamous with a long-term partner and used barrier contraception consistently. She took lorazepam as needed and had no known allergies to medications. The patient lived with her parents and sister in an urban area of New England and worked in an office. She drank alcohol twice weekly and did not smoke tobacco or use illicit drugs. Her paternal grandmother had received a diagnosis of uterine cancer as a young adult, her paternal grandfather had had gastric and prostate cancer, a paternal aunt had had breast cancer, a paternal uncle had had prostate cancer, and her maternal grandmother had died of liver cancer associated with hepatitis C virus. Her parents and sister were healthy.
On examination, the patient appeared well. The temperature was 35.4[degrees]C, the pulse 92 beats per minute, the blood pressure 109/63 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The weight was 52.2 kg, the height 155.6 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.6. The abdomen was soft, without distention or tenderness. Pelvic examination revealed normal female external genitalia and a normal vagina and cervix with scant white discharge; there was a large, mobile pelvic mass extending to the level of the umbilicus. The remainder of the examination was normal. The hemoglobin level, hematocrit, red-cell indexes, platelet count, anion gap, and results of renal-function tests were normal, as were blood levels of electrolytes and glucose; other test results are shown in Table 1. Urinalysis showed clear, yellow urine, with a specific gravity of 1.006, a pH of 7.0, and 1+ ketones on dipstick examination.	
Table 1 
Dr. Weier Li: A transabdominal ultrasound image of the pelvis (Figure 1A) showed a complex left adnexal mass, measuring 13.4 cm by 9.3 cm by 12.9 cm. The mass had cystic components with posterior acoustic enhancement, as well as thickened hypervascular internal septa. The left ovary could not be visualized. There was a small amount of pelvic free fluid. Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, confirmed that the large pelvic mass was probably arising in the left ovary (Figure 1B). The right ovary was normal. An enlarged lymph node, measuring 1.0 cm in diameter, was noted in the left paraaortic area (Figure 1C).	
Figure 1 
Dr. Melamed: Blood tests for lactate dehydrogenase, CA 19-9, carcinoembryonic antigen, CA-125, inhibin A, inhibin B, and alpha-fetoprotein were performed. A follow-up appointment with a gynecologic oncologist was arranged, and the patient was discharged home.
Seven days later, the patient was seen in the gynecologic oncology clinic at this hospital. She reported increased abdominal girth and mild pelvic discomfort that was relieved by ibuprofen. On examination, the patient appeared well, and the vital signs were normal. The abdomen was soft, moderately distended, and mildly tender. There was a large, palpable pelvic mass with limited mobility. The remainder of the examination was unchanged. Laboratory test results that had become available after the patient had been discharged from the emergency department were reviewed (Table 1). A urine test for hCG was positive; other laboratory test results are shown in Table 1.
Management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 24-year-old woman was seen in the emergency department of this hospital because of a pelvic mass.
The patient had been well until 4 weeks before this presentation, when she began to notice an increased frequency of vaginal bleeding. At that time, an episode of vaginal bleeding occurred that lasted for 4 days and resembled her usual menstrual period. Ten days after the end of that bleeding episode, a second episode of similar duration and intensity occurred.
On the morning of this presentation, the patient was evaluated in a local obstetrics and gynecology clinic. The blood human chorionic gonadotropin (hCG) level was 172 IU per liter (reference range in nonpregnant adults, <6). Transabdominal and transvaginal ultrasonography was performed and reportedly revealed a normal-sized uterus, a 17-mm endometrial stripe, and no evidence of an intrauterine pregnancy. There was a complex cyst, measuring 13.1 cm by 8.3 cm by 11.7 cm, around the left adnexa; the cyst contained thickened septa and was composed mainly of large cystic areas with visible motion in the debris. The ovaries were not visualized.
The patient was referred to the emergency department of this hospital for further evaluation. In the emergency department, she reported constipation associated with bowel urgency and mild pelvic pressure. She had generalized anxiety disorder. Menarche had occurred at 16 years of age, and menstrual cycles were irregular, with bleeding typically occurring every 3 months and lasting for 4 days. The patient had never been pregnant and had no known history of sexually transmitted infections or abnormal results on screening tests for cervical cancer. She was monogamous with a long-term partner and used barrier contraception consistently. She took lorazepam as needed and had no known allergies to medications. The patient lived with her parents and sister in an urban area of New England and worked in an office. She drank alcohol twice weekly and did not smoke tobacco or use illicit drugs. Her paternal grandmother had received a diagnosis of uterine cancer as a young adult, her paternal grandfather had had gastric and prostate cancer, a paternal aunt had had breast cancer, a paternal uncle had had prostate cancer, and her maternal grandmother had died of liver cancer associated with hepatitis C virus. Her parents and sister were healthy.
On examination, the patient appeared well. The temperature was 35.4[degrees]C, the pulse 92 beats per minute, the blood pressure 109/63 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The weight was 52.2 kg, the height 155.6 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.6. The abdomen was soft, without distention or tenderness. Pelvic examination revealed normal female external genitalia and a normal vagina and cervix with scant white discharge; there was a large, mobile pelvic mass extending to the level of the umbilicus. The remainder of the examination was normal. The hemoglobin level, hematocrit, red-cell indexes, platelet count, anion gap, and results of renal-function tests were normal, as were blood levels of electrolytes and glucose; other test results are shown in Table 1. Urinalysis showed clear, yellow urine, with a specific gravity of 1.006, a pH of 7.0, and 1+ ketones on dipstick examination.	
Table 1 
Dr. Weier Li: A transabdominal ultrasound image of the pelvis (Figure 1A) showed a complex left adnexal mass, measuring 13.4 cm by 9.3 cm by 12.9 cm. The mass had cystic components with posterior acoustic enhancement, as well as thickened hypervascular internal septa. The left ovary could not be visualized. There was a small amount of pelvic free fluid. Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, confirmed that the large pelvic mass was probably arising in the left ovary (Figure 1B). The right ovary was normal. An enlarged lymph node, measuring 1.0 cm in diameter, was noted in the left paraaortic area (Figure 1C).	
Figure 1 
Dr. Melamed: Blood tests for lactate dehydrogenase, CA 19-9, carcinoembryonic antigen, CA-125, inhibin A, inhibin B, and alpha-fetoprotein were performed. A follow-up appointment with a gynecologic oncologist was arranged, and the patient was discharged home.
Seven days later, the patient was seen in the gynecologic oncology clinic at this hospital. She reported increased abdominal girth and mild pelvic discomfort that was relieved by ibuprofen. On examination, the patient appeared well, and the vital signs were normal. The abdomen was soft, moderately distended, and mildly tender. There was a large, palpable pelvic mass with limited mobility. The remainder of the examination was unchanged. Laboratory test results that had become available after the patient had been discharged from the emergency department were reviewed (Table 1). A urine test for hCG was positive; other laboratory test results are shown in Table 1.
Management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Mature cystic teratoma with malignant transformation to squamous-cell carcinoma. The patient's symptoms of increased vaginal bleeding and the presence of a large, complex cyst in the left adnexa are indicative of an ovarian mass. The ultrasound and CT scan confirmed the presence of a large pelvic mass likely arising from the left ovary. The presence of an enlarged lymph node in the left paraaortic area suggests possible metastasis. The positive urine test for hCG and the elevated levels of CA-125, a marker often elevated in ovarian cancer, further support the diagnosis of a malignant ovarian tumor. The patient's family history of various cancers also increases her risk for developing cancer. The final diagnosis of a mature cystic teratoma with malignant transformation to squamous-cell carcinoma is made based on the histological examination of the removed mass.""
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        ""content"": ""The patient is a 24-year-old woman with a large pelvic mass, irregular menstrual cycles, and a positive hCG test. The ultrasound and CT scan confirmed a complex left adnexal mass, likely arising from the left ovary. The patient also has a family history of various cancers. The positive hCG test, the presence of a large ovarian mass, and the patient's symptoms suggest a germ cell tumor of the ovary, specifically a choriocarcinoma, which is a rare type of cancer that occurs in a woman's reproductive system and produces hCG. \n\nChoriocarcinoma of the ovary.""
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        ""content"": ""The patient is a 24-year-old woman presenting with a pelvic mass, increased frequency of vaginal bleeding, and a positive hCG test. The differential diagnosis includes ectopic pregnancy, ovarian cyst, ovarian torsion, and ovarian cancer. Ectopic pregnancy is less likely given the absence of an intrauterine pregnancy on ultrasound and the size of the mass. Ovarian cyst and torsion are possibilities, but the size of the mass and the presence of thickened septa and visible motion in the debris on ultrasound are more suggestive of a neoplastic process. The patient's family history of various cancers, including uterine cancer in her paternal grandmother, further supports the possibility of a neoplastic process. The positive hCG test could be due to a germ cell tumor, which can produce hCG. The patient's age and the size and characteristics of the mass on imaging are also consistent with a germ cell tumor. \n\nDiagnosis: Ovarian Germ Cell Tumor""
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10.1056/NEJMcpc1900419,"Case 17-2019: A 44-Year-Old Man with Joint Pain, Weight Loss, and Chest Pain","Hemoglobin (g/dl)   6.1
Hematocrit (%)   20.3
Mean corpuscular volume (fl)   72.2
Mean corpuscular hemoglobin (pg) 26. 4.0 21.7
Mean corpuscular hemoglobin level (g/dl) 31. 7.0 30.0
White-cell count (per mm3)   2800
Differential count (%)
Neutrophils   80.7
Lymphocytes   13.3
Monocytes   3.9
Eosinophils   0.7
Basophils   0.0
Platelet count (per mm3)   313,000
Sodium (mmol/liter)   136
Potassium (mmol/liter)   4.0
Chloride (mmol/liter)   101
Carbon dioxide (mmol/liter)   23
Urea nitrogen (mg/dl)   23
Creatinine (mg/dl)   0.95
Glucose (mg/dl)   73
Calcium (mg/dl)   7.9
Total protein (g/dl) 6. .3 5.7
Albumin (g/dl)   2.5
Alanine aminotransferase (U/liter)   58
Aspartate aminotransferase (U/liter)   70
Alkaline phosphatase (U/liter)   252
Troponin T (ng/ml) <0.03  
Erythrocyte sedimentation rate (mm/hr)   105
C-reactive protein (mg/liter)  .0 86.0
Lactate dehydrogenase (U/liter) 11 10 273
Iron (μg/dl)  9
Iron-binding capacity (μg/dl) 23 4 103
Ferritin (μg/liter) 1 00 1921",Systemic lupus erythematosus.,Systemic lupus erythematosus.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 44-year-old man was admitted to this hospital because of joint pain, unintentional weight loss, and chest pain.
Ten months before admission, arthralgias developed in the shoulders. After 2 months of discomfort, the patient was evaluated by a rheumatologist at another hospital. Magnetic resonance imaging (MRI) of the shoulders was reportedly normal. Piroxicam was prescribed, and glucocorticoid injections to the shoulders were administered. During the next 4 months, arthralgias developed in the fingers and knees. A diagnosis of fibromyalgia was made by the rheumatologist. Naproxen was prescribed at a dose of 250 to 500 mg two or three times daily, as needed, and additional glucocorticoid injections to the shoulders were administered.
Six weeks before admission, anorexia, odynophagia, and epigastric pain developed. Two weeks later, the patient began to have episodic anterior pleuritic pain, which was characterized as sharp and was worse when he was in the supine position; he also had intermittent dyspnea and nonproductive cough. He had fatigue that was sometimes severe enough to prevent him from getting out of bed. One week before admission, subjective fevers and increased dyspnea occurred.
One day before admission, the patient's sister thought that the patient appeared weak and ill and took him to the emergency department of a second hospital. Laboratory test results were notable for a white-cell count of 2000 per cubic millimeter (normal range, 4500 to 11,000) and a hematocrit of 21% (normal range, 41 to 53). Imaging studies were obtained.
Dr. Andrew S. Fox: A posteroanterior chest radiograph showed an enlarged cardiac silhouette, changes consistent with small bilateral pleural effusions, and mild interstitial pulmonary edema (Figure 1A). Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed small-volume ascites with peritoneal enhancement (Figure 1B), a moderate-to-large circumferential pericardial effusion, and small bilateral pleural effusions (Figure 1C).	
Figure 1 
Dr. Schoenfeld: The patient was transferred to the emergency department of this hospital for further evaluation and treatment. A review of systems was notable for fatigue, mild bilateral joint pain, pleuritic pain, intermittent dyspnea, nonproductive cough, anorexia, odynophagia, an unintentional weight loss of 18 kg during the past year, polyuria, and a pruritic rash on the arms that had some sloughing and spared the hands. He had no night sweats, chills, melena, hematochezia, diarrhea, photosensitivity, dry eyes or mouth, Raynaud's phenomenon, urinary symptoms, penile lesion or discharge, orthopnea, or edema.
The patient's medical history was notable for malaria and depression. Medications included bupropion and naproxen as needed. Diphenhydramine had caused oral and facial swelling and pruritus. The patient was born and raised in sub-Saharan Africa and had immigrated to New England 18 years earlier; he had not traveled outside the United States in 15 years. He was currently unemployed. He was divorced and had been sexually active with women, most recently 7 months before the current presentation. He lived with his sister and his two young children; one son had had symptoms of an upper respiratory infection 2 weeks earlier. The patient reported that he had had a 7-year period of heavy beer drinking but had been abstinent for almost 20 years; he had smoked 1 pack of cigarettes daily for 12 years but had quit 15 years earlier. There was no history of illicit drug use. There was no family history of heart disease, human immunodeficiency virus (HIV) infection, tuberculosis, autoimmune disease, or cancer.
On examination, the temperature was 37.7[degrees]C, the heart rate 100 beats per minute, the blood pressure 93/57 mm Hg (pulsus paradoxus, 12 mm Hg), the respiratory rate 18 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The height was 173 cm, the weight 54.3 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 18.1. The patient had signs of chronic illness, including cachexia and bitemporal wasting. The jugular venous pressure was 14 cm of water. He had a yellow coating on the tongue but no lesions in the mouth. He had scaling and dry skin on the arms and chest but no overt rash. Diffuse subcentimeter lymph nodes in the cervical chain were palpable, as were larger bilateral axillary lymph nodes. The heart rhythm was tachycardic and distant, and the lungs were clear. There was mild epigastric tenderness, without rebound or guarding. Shoulder abduction was limited to 90 degrees bilaterally, and there was pain on external rotation. The knees were warm, with moderate effusions, and there was pain on knee flexion. The patient had synovitis and tenderness of the wrists and proximal interphalangeal joints. The rest of the examination was normal.
Results of blood tests for phosphorus, magnesium, bilirubin, amylase, lipase, and thyrotropin were normal; additional laboratory test results are shown in Table 1. Urinalysis was notable for yellow, slightly cloudy urine, with 1+ urobilinogen (normal value, negative), 2+ protein (normal value, negative), 0 to 2 erythrocytes per high-power field (normal range, 0 to 2), and 3 to 5 leukocytes per high-power field (normal range,  ). An electrocardiogram showed sinus rhythm at a rate of 96 beats per minute, subtle PR-segment depression, and borderline low limb-lead voltage. A chest radiograph showed an enlarged cardiac silhouette and small bilateral pleural effusions. Echocardiography was performed.	
Table 1 
Dr. Varsha K. Tanguturi: Echocardiography revealed normal left ventricular size and function. There was a moderate-sized pericardial effusion with diffuse fibrin deposition. There was brief right ventricular diastolic inversion without substantial respirophasic variation (i.e., variation from expiration to inspiration) in the intracardiac Doppler-flow velocities. The inferior vena cava was not dilated.
Dr. Schoenfeld: Intravenous normal saline and esomeprazole were administered, and the patient was admitted to the cardiology unit of this hospital.
On the second day, the patient's temperature reached 39.1[degrees]C. Blood specimens were obtained for culture, and an induced-sputum specimen was obtained for microbiologic studies, including mycobacterial smear and culture. Testing of a nasopharyngeal sample was negative for influenza A and B. Screening tests for HIV types 1 and 2 and HIV p24 antigen, antibodies to Lyme disease, and heterophile antibodies were negative. Serologic testing for IgG antibodies to cytomegalovirus was positive. A purified protein derivative was planted to assess for a response to Mycobacterium tuberculosis antigens. The systolic blood pressure remained within a range of 90 to 100 mm Hg, with the heart rate ranging from 100 to 110 beats per minute; runs of nonsustained ventricular tachycardia occurred, the longest of which was 28 beats. Intravenous magnesium and amiodarone were administered.
On the third day, the patient's temperature reached 39.7[degrees]C. The systolic blood pressure remained within a range of 90 to 100 mm Hg, and runs of nonsustained ventricular tachycardia persisted. The prothrombin time was 14.5 seconds (normal range, 11.0 to 14.0), the partial-thromboplastin time 36.4 seconds (normal range, 22.0 to 35.0), and the prothrombin-time international normalized ratio 1.1 (normal range, 0.9 to 1.1). Additional imaging studies were obtained.
Dr. Fox: CT of the chest, performed after the administration of intravenous contrast material, revealed enlargement of the bilateral pleural effusions to a moderate size, with loculation of pleural effusions on the right side, as well as enlargement of the pericardial effusion (Figure 1D). There were enlarged bilateral axillary lymph nodes (Figure 1E).
Dr. Schoenfeld: On the fourth day, the patient's temperature was 38.8[degrees]C. The heart rate increased to 120 beats per minute, and the systolic blood pressure was 80 to 90 mm Hg.
Dr. Tanguturi: Repeat echocardiography revealed preserved left ventricular function. There was a large circumferential pericardial effusion (measuring 3 cm); the pericardial effusion was larger than it had been on the echocardiogram obtained 3 days earlier and was causing diastolic inversion of the right ventricular free wall and right atrium (Figure 2). The presence of right ventricular diastolic inversion suggests increased intrapericardial pressure and a 20% decrease in cardiac output, and the presence of right atrial compression during more than one third of the cardiac cycle is nearly 100% sensitive and specific for tamponade.1 There was diffuse fibrin deposition along the visceral pericardium, a finding suggestive of chronicity. There was respirophasic variation of 40% in the Doppler-flow velocities across the mitral valve. Respirophasic variation of at least 30% in the Doppler-flow velocities across the mitral valve is considered to be suggestive of cardiac tamponade caused by increased filling of the right ventricle during inspiration, with compression of the right ventricular free wall and subsequent decreased filling of the left ventricle.1 There was new dilatation of the inferior vena cava without compression during inspiration, a finding suggestive of elevated pressures on the right side of the heart.	
Figure 2 
Catheterization of the right side of the heart revealed elevation and equalization of diastolic pressures, with a right atrial pressure of 20 mm Hg, a right ventricular end-diastolic pressure of 24 mm Hg, and a pulmonary capillary wedge pressure of 20 mm Hg; these findings are consistent with cardiac tamponade. Pericardiocentesis was notable for retrieval of 570 ml of bloody fluid, which reduced the intrapericardial pressure from 18 mm Hg to 3 mm Hg.
Dr. Schoenfeld: Gram's staining of the pericardial fluid revealed abundant neutrophils and very few mononuclear cells but no organisms. The glucose level was 77 mg per deciliter (4.3 mmol per liter), the lactate dehydrogenase level 1487 U per liter, and the total protein level 4.0 g per deciliter. The red-cell count was 18,000 per cubic millimeter, and the nucleated-cell count 9439 per cubic millimeter, 93% of which were neutrophils. Microbiologic culture of the pericardial fluid was also performed. Cytologic examination of the pericardial fluid for malignant cells was negative, as were additional blood tests, including an interferon-[gamma] release assay for tuberculosis and tests for rheumatoid factor, antitreponemal antibodies, antibodies to hepatitis B virus, and IgM antibodies to parvovirus.
Diagnostic test results were received, and additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 44-year-old man was admitted to this hospital because of joint pain, unintentional weight loss, and chest pain.
Ten months before admission, arthralgias developed in the shoulders. After 2 months of discomfort, the patient was evaluated by a rheumatologist at another hospital. Magnetic resonance imaging (MRI) of the shoulders was reportedly normal. Piroxicam was prescribed, and glucocorticoid injections to the shoulders were administered. During the next 4 months, arthralgias developed in the fingers and knees. A diagnosis of fibromyalgia was made by the rheumatologist. Naproxen was prescribed at a dose of 250 to 500 mg two or three times daily, as needed, and additional glucocorticoid injections to the shoulders were administered.
Six weeks before admission, anorexia, odynophagia, and epigastric pain developed. Two weeks later, the patient began to have episodic anterior pleuritic pain, which was characterized as sharp and was worse when he was in the supine position; he also had intermittent dyspnea and nonproductive cough. He had fatigue that was sometimes severe enough to prevent him from getting out of bed. One week before admission, subjective fevers and increased dyspnea occurred.
One day before admission, the patient's sister thought that the patient appeared weak and ill and took him to the emergency department of a second hospital. Laboratory test results were notable for a white-cell count of 2000 per cubic millimeter (normal range, 4500 to 11,000) and a hematocrit of 21% (normal range, 41 to 53). Imaging studies were obtained.
Dr. Andrew S. Fox: A posteroanterior chest radiograph showed an enlarged cardiac silhouette, changes consistent with small bilateral pleural effusions, and mild interstitial pulmonary edema (Figure 1A). Computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed small-volume ascites with peritoneal enhancement (Figure 1B), a moderate-to-large circumferential pericardial effusion, and small bilateral pleural effusions (Figure 1C).	
Figure 1 
Dr. Schoenfeld: The patient was transferred to the emergency department of this hospital for further evaluation and treatment. A review of systems was notable for fatigue, mild bilateral joint pain, pleuritic pain, intermittent dyspnea, nonproductive cough, anorexia, odynophagia, an unintentional weight loss of 18 kg during the past year, polyuria, and a pruritic rash on the arms that had some sloughing and spared the hands. He had no night sweats, chills, melena, hematochezia, diarrhea, photosensitivity, dry eyes or mouth, Raynaud's phenomenon, urinary symptoms, penile lesion or discharge, orthopnea, or edema.
The patient's medical history was notable for malaria and depression. Medications included bupropion and naproxen as needed. Diphenhydramine had caused oral and facial swelling and pruritus. The patient was born and raised in sub-Saharan Africa and had immigrated to New England 18 years earlier; he had not traveled outside the United States in 15 years. He was currently unemployed. He was divorced and had been sexually active with women, most recently 7 months before the current presentation. He lived with his sister and his two young children; one son had had symptoms of an upper respiratory infection 2 weeks earlier. The patient reported that he had had a 7-year period of heavy beer drinking but had been abstinent for almost 20 years; he had smoked 1 pack of cigarettes daily for 12 years but had quit 15 years earlier. There was no history of illicit drug use. There was no family history of heart disease, human immunodeficiency virus (HIV) infection, tuberculosis, autoimmune disease, or cancer.
On examination, the temperature was 37.7[degrees]C, the heart rate 100 beats per minute, the blood pressure 93/57 mm Hg (pulsus paradoxus, 12 mm Hg), the respiratory rate 18 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The height was 173 cm, the weight 54.3 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 18.1. The patient had signs of chronic illness, including cachexia and bitemporal wasting. The jugular venous pressure was 14 cm of water. He had a yellow coating on the tongue but no lesions in the mouth. He had scaling and dry skin on the arms and chest but no overt rash. Diffuse subcentimeter lymph nodes in the cervical chain were palpable, as were larger bilateral axillary lymph nodes. The heart rhythm was tachycardic and distant, and the lungs were clear. There was mild epigastric tenderness, without rebound or guarding. Shoulder abduction was limited to 90 degrees bilaterally, and there was pain on external rotation. The knees were warm, with moderate effusions, and there was pain on knee flexion. The patient had synovitis and tenderness of the wrists and proximal interphalangeal joints. The rest of the examination was normal.
Results of blood tests for phosphorus, magnesium, bilirubin, amylase, lipase, and thyrotropin were normal; additional laboratory test results are shown in Table 1. Urinalysis was notable for yellow, slightly cloudy urine, with 1+ urobilinogen (normal value, negative), 2+ protein (normal value, negative), 0 to 2 erythrocytes per high-power field (normal range, 0 to 2), and 3 to 5 leukocytes per high-power field (normal range,  ). An electrocardiogram showed sinus rhythm at a rate of 96 beats per minute, subtle PR-segment depression, and borderline low limb-lead voltage. A chest radiograph showed an enlarged cardiac silhouette and small bilateral pleural effusions. Echocardiography was performed.	
Table 1 
Dr. Varsha K. Tanguturi: Echocardiography revealed normal left ventricular size and function. There was a moderate-sized pericardial effusion with diffuse fibrin deposition. There was brief right ventricular diastolic inversion without substantial respirophasic variation (i.e., variation from expiration to inspiration) in the intracardiac Doppler-flow velocities. The inferior vena cava was not dilated.
Dr. Schoenfeld: Intravenous normal saline and esomeprazole were administered, and the patient was admitted to the cardiology unit of this hospital.
On the second day, the patient's temperature reached 39.1[degrees]C. Blood specimens were obtained for culture, and an induced-sputum specimen was obtained for microbiologic studies, including mycobacterial smear and culture. Testing of a nasopharyngeal sample was negative for influenza A and B. Screening tests for HIV types 1 and 2 and HIV p24 antigen, antibodies to Lyme disease, and heterophile antibodies were negative. Serologic testing for IgG antibodies to cytomegalovirus was positive. A purified protein derivative was planted to assess for a response to Mycobacterium tuberculosis antigens. The systolic blood pressure remained within a range of 90 to 100 mm Hg, with the heart rate ranging from 100 to 110 beats per minute; runs of nonsustained ventricular tachycardia occurred, the longest of which was 28 beats. Intravenous magnesium and amiodarone were administered.
On the third day, the patient's temperature reached 39.7[degrees]C. The systolic blood pressure remained within a range of 90 to 100 mm Hg, and runs of nonsustained ventricular tachycardia persisted. The prothrombin time was 14.5 seconds (normal range, 11.0 to 14.0), the partial-thromboplastin time 36.4 seconds (normal range, 22.0 to 35.0), and the prothrombin-time international normalized ratio 1.1 (normal range, 0.9 to 1.1). Additional imaging studies were obtained.
Dr. Fox: CT of the chest, performed after the administration of intravenous contrast material, revealed enlargement of the bilateral pleural effusions to a moderate size, with loculation of pleural effusions on the right side, as well as enlargement of the pericardial effusion (Figure 1D). There were enlarged bilateral axillary lymph nodes (Figure 1E).
Dr. Schoenfeld: On the fourth day, the patient's temperature was 38.8[degrees]C. The heart rate increased to 120 beats per minute, and the systolic blood pressure was 80 to 90 mm Hg.
Dr. Tanguturi: Repeat echocardiography revealed preserved left ventricular function. There was a large circumferential pericardial effusion (measuring 3 cm); the pericardial effusion was larger than it had been on the echocardiogram obtained 3 days earlier and was causing diastolic inversion of the right ventricular free wall and right atrium (Figure 2). The presence of right ventricular diastolic inversion suggests increased intrapericardial pressure and a 20% decrease in cardiac output, and the presence of right atrial compression during more than one third of the cardiac cycle is nearly 100% sensitive and specific for tamponade.1 There was diffuse fibrin deposition along the visceral pericardium, a finding suggestive of chronicity. There was respirophasic variation of 40% in the Doppler-flow velocities across the mitral valve. Respirophasic variation of at least 30% in the Doppler-flow velocities across the mitral valve is considered to be suggestive of cardiac tamponade caused by increased filling of the right ventricle during inspiration, with compression of the right ventricular free wall and subsequent decreased filling of the left ventricle.1 There was new dilatation of the inferior vena cava without compression during inspiration, a finding suggestive of elevated pressures on the right side of the heart.	
Figure 2 
Catheterization of the right side of the heart revealed elevation and equalization of diastolic pressures, with a right atrial pressure of 20 mm Hg, a right ventricular end-diastolic pressure of 24 mm Hg, and a pulmonary capillary wedge pressure of 20 mm Hg; these findings are consistent with cardiac tamponade. Pericardiocentesis was notable for retrieval of 570 ml of bloody fluid, which reduced the intrapericardial pressure from 18 mm Hg to 3 mm Hg.
Dr. Schoenfeld: Gram's staining of the pericardial fluid revealed abundant neutrophils and very few mononuclear cells but no organisms. The glucose level was 77 mg per deciliter (4.3 mmol per liter), the lactate dehydrogenase level 1487 U per liter, and the total protein level 4.0 g per deciliter. The red-cell count was 18,000 per cubic millimeter, and the nucleated-cell count 9439 per cubic millimeter, 93% of which were neutrophils. Microbiologic culture of the pericardial fluid was also performed. Cytologic examination of the pericardial fluid for malignant cells was negative, as were additional blood tests, including an interferon-[gamma] release assay for tuberculosis and tests for rheumatoid factor, antitreponemal antibodies, antibodies to hepatitis B virus, and IgM antibodies to parvovirus.
Diagnostic test results were received, and additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of joint pain, unintentional weight loss, chest pain, and fever, along with the findings of pericardial effusion and cardiac tamponade, suggest an inflammatory or infectious process. The patient's history of malaria and residence in sub-Saharan Africa raise the possibility of a tropical infectious disease. However, the patient has not traveled outside the United States in 15 years, making this less likely. The patient's symptoms did not improve with anti-inflammatory medications, suggesting that the cause is not a simple inflammatory condition like fibromyalgia. The presence of neutrophils in the pericardial fluid suggests an acute inflammatory response, but no organisms were found on Gram stain and cultures were negative, making an infectious cause less likely. The patient's history of heavy drinking could suggest alcoholic cardiomyopathy, but this would not explain the joint pain or weight loss. The presence of bilateral pleural effusions and lymphadenopathy on imaging could suggest a malignancy, but cytologic examination of the pericardial fluid was negative for malignant cells. The patient's symptoms and findings are consistent with an autoimmune or connective tissue disease, such as lupus or rheumatoid arthritis, but tests for rheumatoid factor were negative. The patient's symptoms, along with the findings of pericardial effusion and cardiac tamponade, are consistent with a diagnosis of systemic lupus erythematosus (SLE), even in the absence of a positive test for antinuclear antibodies, which is not always present in SLE.\n\nDiagnosis: Systemic Lupus Erythematosus (SLE)""
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        ""content"": ""The patient's symptoms of joint pain, unintentional weight loss, chest pain, and fever, along with the findings of pericardial effusion and cardiac tamponade, suggest a systemic inflammatory process. The patient's history of malaria and residence in sub-Saharan Africa raise the possibility of a chronic infectious disease. However, the negative results of tests for HIV, Lyme disease, and tuberculosis, as well as the lack of response to antibiotics, make an infectious cause less likely. The patient's symptoms and the presence of pericardial effusion also suggest a possible autoimmune disease, but tests for rheumatoid factor were negative. The patient's history of heavy drinking could suggest alcoholic cardiomyopathy, but this would not explain the joint pain or weight loss. The presence of neutrophils in the pericardial fluid suggests an inflammatory process. Given the patient's symptoms and test results, the most likely diagnosis is an autoimmune or inflammatory disease, possibly lupus, although this is not confirmed by the information given.\n\nDiagnosis: Systemic lupus erythematosus (SLE) or another autoimmune disease.""
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        ""content"": ""The patient is a 44-year-old man presenting with joint pain, unintentional weight loss, and chest pain. He has a history of malaria and depression. His symptoms include fatigue, mild bilateral joint pain, pleuritic pain, intermittent dyspnea, nonproductive cough, anorexia, odynophagia, an unintentional weight loss of 18 kg during the past year, polyuria, and a pruritic rash on the arms that had some sloughing and spared the hands. He also has a history of heavy beer drinking and smoking. The differential diagnosis for this patient includes rheumatoid arthritis, lupus, tuberculosis, HIV, and malignancy. The patient's joint pain and rash could be indicative of rheumatoid arthritis or lupus, but his lack of other symptoms such as photosensitivity, dry eyes or mouth, and Raynaud's phenomenon make these diagnoses less likely. His history of malaria and immigration from sub-Saharan Africa could suggest tuberculosis, but his negative purified protein derivative test and lack of night sweats or chills make this less likely. His history of heavy beer drinking and smoking could suggest a malignancy, but his negative cytologic examination of the pericardial fluid for malignant cells makes this less likely. His unintentional weight loss, fatigue, and anorexia could suggest HIV, but his negative screening tests for HIV types 1 and 2 and HIV p24 antigen make this less likely. The patient's symptoms, history, and test results are most consistent with a diagnosis of Still's disease, a rare type of arthritis that can cause fever, rash, and joint pain. \n\nDiagnosis: Still's disease.""
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10.1056/NEJMcpc1900595,Case 16-2019: A 53-Year-Old Man with Cough and Eosinophilia,"Hemoglobin (g/dl)   15.3 14.8
Hematocrit (%)   42.8 40.2
White-cell count (per mm3)   11,900 13,800
Differential count (%)
Polymorphonuclear cells   36 37
Lymphocytes   25 25
Monocytes   6 4
Eosinophils   32 33
Basophils   1 1
Platelet count (per mm3
)   319,000 314,000
IgE (IU/ml) 0–100 1900
Antinuclear antibody Negative at 1:40 
and 1:160
Positive at 1:40 and 1:160, 
speckled pattern",Tropical pulmonary eosinophilia,Tropical pulmonary eosinophilia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 53-year-old man was evaluated in an urgent care clinic of this hospital for 3 months of cough.
Five years before the current evaluation, the patient began to have exertional dyspnea and received a diagnosis of hypertrophic obstructive cardiomyopathy, with a resting left ventricular outflow gradient of 110 mm Hg on echocardiography. Although he received medical therapy, symptoms persisted, and percutaneous alcohol septal ablation was performed 1 year before the current evaluation, with resolution of the exertional dyspnea.
Nine months later, the patient began to have cough that was intermittently productive of yellow sputum. The cough developed shortly after he had returned from travel to Southeast Asia and the Middle East. Antitussive medications did not provide symptom relief. Three years before this cough developed, three discrete episodes of upper respiratory tract infection and sinusitis had occurred, for which courses of amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, and azithromycin had been prescribed. During the current episode, the cough waxed and waned in intensity, with no clear relation to other symptoms or the time of day.
Ten days before the current evaluation, the patient traveled to the Middle East; the weather was colder than he had expected and he felt chills. During the trip, the cough worsened - with more frequent and copious production of yellow-green sputum and associated coryza, pharyngitis, frontal sinus ""heaviness,"" malaise, and fatigue - such that he had to miss work after he returned home. He called his cardiologist and was advised to present to an urgent care clinic of this hospital for evaluation.
A review of systems was negative for fever, anorexia, unintentional weight loss, night sweats, dyspnea, hemoptysis, chest pressure or discomfort, pleuritic pain, wheezing, light-headedness, palpitations, syncope, nausea, vomiting, diarrhea, myalgia, arthralgia, lymphadenopathy, and pruritus. The patient had had multiple contacts with nonspecific illnesses while he had been traveling both 3 months and 10 days before the current evaluation. The most recent tuberculin skin test had been performed 10 years earlier and had been negative. He had not undergone seasonal influenza vaccination.
The patient's medical history was also notable for placement of an implantable cardioverter-defibrillator (ICD) for ventricular tachycardia that had been induced during an electrophysiological study. He had allergic rhinitis, obstructive sleep apnea, gonococcal urethritis, and dyslipidemia. Medications included metoprolol succinate and atorvastatin. He had had no known adverse reactions to medications, except prolongation of the corrected QT interval with disopyramide.
The patient was born in South Asia, raised in the Middle East, and educated in the United States, where he had lived for the past 25 years. He was an executive and traveled frequently for work, generally to urban areas and only rarely to rural areas, although he had walked barefoot near beaches in various locations in Southeast Asia. He was divorced and had a child. He smoked cigars occasionally and drank 1 to 2 glasses of wine nightly but did not use illicit substances. He had been sexually active while traveling but had used condoms. Several first-degree relatives had hypertrophic cardiomyopathy. His mother had died 3 years earlier from pulmonary tuberculosis, but he had not been in contact with her during her illness.
On examination, the patient appeared to be comfortable. The temperature was 37.2[degrees]C, the pulse 66 beats per minute, the blood pressure 122/89 mm Hg, the respiratory rate 14 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. During the evaluation, the patient coughed twice, and the second cough produced light-green sputum with a bloody streak. The oropharynx had no erythema or exudates, but there was a slight yellow discoloration on the tongue. There was no tenderness on percussion of the sinuses or conjunctival hyperemia. There was no cervical, submandibular, supraclavicular, or axillary lymphadenopathy. Auscultation revealed a clear chest, without rales, wheezing, or egophony. The jugular venous pulse was 6 cm of water. There was a crescendo-decrescendo systolic murmur (grade 3/6) along the left sternal border that increased during a Valsalva maneuver. There was no edema or calf tenderness. The remainder of the examination was normal.
Dr. Jo-Anne O. Shepard: A posteroanterior chest radiograph (Figure 1) showed clear lungs and a slightly enlarged heart, findings that had not changed from a study obtained 1 year earlier. There was a dual-lead ICD that terminated in the right atrium and right ventricle.	
Figure 1 
Dr. Dudzinski: An electrocardiogram (Figure 2) was notable for sinus rhythm, left ventricular hypertrophy, and T-wave inversions in leads I, aVL, V4, V5, and V6, findings that had not changed from previous tracings. A 5-day course of azithromycin was prescribed, along with acetaminophen, oxymetazoline nasal spray, and a phenol-based topical throat spray. A tuberculin skin test was negative for induration. Results of liver-function tests were normal; other laboratory test results are shown in Table 1. A transthoracic echocardiogram was notable for a left ventricular ejection fraction of 60%, a maximum left ventricular wall thickness of 16 mm, systolic anterior motion of the mitral-valve chordae with trace mitral regurgitation, and a resting left ventricular outflow gradient of 16 mm Hg; these findings had not changed from a study obtained 9 months earlier.	
Figure 2 
Azithromycin therapy resulted in decreased fatigue and malaise and reduced the frequency of the cough but did not eliminate it. A few episodes of hemoptysis with scant blood occurred, and bloody streaks were present in nasal mucus. After the patient completed the course of azithromycin, additional laboratory tests were performed (Table 1). Cultures of the stool and sputum were negative, as was examination of the stool and sputum for ova and parasites. A hypersensitivity pneumonitis panel (including a test for antibodies to aspergillus) was also negative, as were tests for galactomannan, 1,3-[beta]-d-glucan, and antibodies to human immunodeficiency virus types 1 and 2. Testing for antibodies to paragonimus was negative, but testing for antibodies to strongyloides was positive.
Additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 53-year-old man was evaluated in an urgent care clinic of this hospital for 3 months of cough.
Five years before the current evaluation, the patient began to have exertional dyspnea and received a diagnosis of hypertrophic obstructive cardiomyopathy, with a resting left ventricular outflow gradient of 110 mm Hg on echocardiography. Although he received medical therapy, symptoms persisted, and percutaneous alcohol septal ablation was performed 1 year before the current evaluation, with resolution of the exertional dyspnea.
Nine months later, the patient began to have cough that was intermittently productive of yellow sputum. The cough developed shortly after he had returned from travel to Southeast Asia and the Middle East. Antitussive medications did not provide symptom relief. Three years before this cough developed, three discrete episodes of upper respiratory tract infection and sinusitis had occurred, for which courses of amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, and azithromycin had been prescribed. During the current episode, the cough waxed and waned in intensity, with no clear relation to other symptoms or the time of day.
Ten days before the current evaluation, the patient traveled to the Middle East; the weather was colder than he had expected and he felt chills. During the trip, the cough worsened - with more frequent and copious production of yellow-green sputum and associated coryza, pharyngitis, frontal sinus ""heaviness,"" malaise, and fatigue - such that he had to miss work after he returned home. He called his cardiologist and was advised to present to an urgent care clinic of this hospital for evaluation.
A review of systems was negative for fever, anorexia, unintentional weight loss, night sweats, dyspnea, hemoptysis, chest pressure or discomfort, pleuritic pain, wheezing, light-headedness, palpitations, syncope, nausea, vomiting, diarrhea, myalgia, arthralgia, lymphadenopathy, and pruritus. The patient had had multiple contacts with nonspecific illnesses while he had been traveling both 3 months and 10 days before the current evaluation. The most recent tuberculin skin test had been performed 10 years earlier and had been negative. He had not undergone seasonal influenza vaccination.
The patient's medical history was also notable for placement of an implantable cardioverter-defibrillator (ICD) for ventricular tachycardia that had been induced during an electrophysiological study. He had allergic rhinitis, obstructive sleep apnea, gonococcal urethritis, and dyslipidemia. Medications included metoprolol succinate and atorvastatin. He had had no known adverse reactions to medications, except prolongation of the corrected QT interval with disopyramide.
The patient was born in South Asia, raised in the Middle East, and educated in the United States, where he had lived for the past 25 years. He was an executive and traveled frequently for work, generally to urban areas and only rarely to rural areas, although he had walked barefoot near beaches in various locations in Southeast Asia. He was divorced and had a child. He smoked cigars occasionally and drank 1 to 2 glasses of wine nightly but did not use illicit substances. He had been sexually active while traveling but had used condoms. Several first-degree relatives had hypertrophic cardiomyopathy. His mother had died 3 years earlier from pulmonary tuberculosis, but he had not been in contact with her during her illness.
On examination, the patient appeared to be comfortable. The temperature was 37.2[degrees]C, the pulse 66 beats per minute, the blood pressure 122/89 mm Hg, the respiratory rate 14 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. During the evaluation, the patient coughed twice, and the second cough produced light-green sputum with a bloody streak. The oropharynx had no erythema or exudates, but there was a slight yellow discoloration on the tongue. There was no tenderness on percussion of the sinuses or conjunctival hyperemia. There was no cervical, submandibular, supraclavicular, or axillary lymphadenopathy. Auscultation revealed a clear chest, without rales, wheezing, or egophony. The jugular venous pulse was 6 cm of water. There was a crescendo-decrescendo systolic murmur (grade 3/6) along the left sternal border that increased during a Valsalva maneuver. There was no edema or calf tenderness. The remainder of the examination was normal.
Dr. Jo-Anne O. Shepard: A posteroanterior chest radiograph (Figure 1) showed clear lungs and a slightly enlarged heart, findings that had not changed from a study obtained 1 year earlier. There was a dual-lead ICD that terminated in the right atrium and right ventricle.	
Figure 1 
Dr. Dudzinski: An electrocardiogram (Figure 2) was notable for sinus rhythm, left ventricular hypertrophy, and T-wave inversions in leads I, aVL, V4, V5, and V6, findings that had not changed from previous tracings. A 5-day course of azithromycin was prescribed, along with acetaminophen, oxymetazoline nasal spray, and a phenol-based topical throat spray. A tuberculin skin test was negative for induration. Results of liver-function tests were normal; other laboratory test results are shown in Table 1. A transthoracic echocardiogram was notable for a left ventricular ejection fraction of 60%, a maximum left ventricular wall thickness of 16 mm, systolic anterior motion of the mitral-valve chordae with trace mitral regurgitation, and a resting left ventricular outflow gradient of 16 mm Hg; these findings had not changed from a study obtained 9 months earlier.	
Figure 2 
Azithromycin therapy resulted in decreased fatigue and malaise and reduced the frequency of the cough but did not eliminate it. A few episodes of hemoptysis with scant blood occurred, and bloody streaks were present in nasal mucus. After the patient completed the course of azithromycin, additional laboratory tests were performed (Table 1). Cultures of the stool and sputum were negative, as was examination of the stool and sputum for ova and parasites. A hypersensitivity pneumonitis panel (including a test for antibodies to aspergillus) was also negative, as were tests for galactomannan, 1,3-[beta]-d-glucan, and antibodies to human immunodeficiency virus types 1 and 2. Testing for antibodies to paragonimus was negative, but testing for antibodies to strongyloides was positive.
Additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of cough, intermittent production of yellow sputum, and recent travel to Southeast Asia and the Middle East suggest a possible infectious cause. The patient's symptoms did not completely resolve with azithromycin, suggesting that the cause of the cough may not be a typical bacterial infection. The patient tested positive for antibodies to strongyloides, which is a parasitic infection that can cause respiratory symptoms including cough. This, combined with the patient's history of travel to areas where strongyloides is endemic, suggests that the patient's symptoms may be due to a strongyloides infection.\n\nStrongyloides stercoralis infection.""
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        ""content"": ""The patient is a 53-year-old man with a history of hypertrophic obstructive cardiomyopathy, presenting with a 3-month history of cough that is intermittently productive of yellow sputum. The cough began after he returned from travel to Southeast Asia and the Middle East. The patient's medical history is also notable for placement of an implantable cardioverter-defibrillator (ICD) for ventricular tachycardia, allergic rhinitis, obstructive sleep apnea, gonococcal urethritis, and dyslipidemia. He has had multiple contacts with nonspecific illnesses while traveling. He was born in South Asia, raised in the Middle East, and has lived in the United States for the past 25 years. He travels frequently for work, generally to urban areas and only rarely to rural areas, although he has walked barefoot near beaches in various locations in Southeast Asia. His mother had died 3 years earlier from pulmonary tuberculosis, but he had not been in contact with her during her illness. \n\nThe differential diagnosis for this patient includes tuberculosis, pneumonia, bronchitis, and parasitic infection. Given the patient's travel history and the fact that his mother died from pulmonary tuberculosis, tuberculosis should be considered. However, the patient's tuberculin skin test was negative, making this less likely. Pneumonia and bronchitis could also cause the patient's symptoms, but these would typically present with fever, which the patient does not have. The patient's positive test for antibodies to strongyloides suggests a parasitic infection. Strongyloides stercoralis is a parasitic roundworm that can cause a variety of symptoms, including cough, and is endemic in many parts of the world, including Southeast Asia. \n\nDiagnosis: Strongyloides stercoralis infection.""
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10.1056/NEJMcpc1900592,Case 15-2019: A 55-Year-Old Man with Jaundice,"Prothrombin time (sec)   20.0
Prothrombin-time international normalized ratio   1.7
Alanine aminotransferase (U/liter)   1299 2698
Aspartate aminotransferase (U/liter)   779 2869
Bilirubin (mg/dl)†
Total 1.7 21.6
Direct  18.6
Alkaline phosphatase (U/liter)   213 150
Protein (g/dl)
Total 6. .3 6.7 5.4
Albumin   4.0 3.4
Globulin   2.7 2.0
C-reactive protein (mg/liter)  .0 31.5
Hepatitis C virus antibody Negative Positive Positive
Hepatitis C virus RNA (IU/ml) <15 68,172 <15
Human immunodeficiency virus p24 antigen 
and type 1 and type 2 antibodies
Negative Negative",Acute hepatitis B virus and hepatitis delta virus coinfection in the presence of chronic hepatitis C virus infection,Acute hepatitis B virus infection in the presence of chronic hepatitis C virus infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 55-year-old man with a history of opioid use disorder and hepatitis C virus (HCV) infection presented to this hospital with jaundice.
Four months before the current presentation, the patient was released from prison after a 2-year incarceration. After he left prison, he resumed injecting heroin and had three episodes of overdose. He was evaluated at another hospital for symptoms of depression and was admitted for psychiatric treatment. During that admission, sublingual buprenorphine-naloxone therapy was initiated, and the patient was discharged.
One day after discharge and 5 weeks before the current presentation, headache, body aches, sweats, diarrhea, and nausea developed. The patient presented to a clinic for substance use disorder that is affiliated with the other hospital and reported that he had been unable to obtain sublingual buprenorphine-naloxone from a pharmacy after discharge. The temperature was 36.6[degrees]C, the pulse 70 beats per minute, and the blood pressure 100/68 mm Hg. The weight was 72 kg. He appeared to be restless, but the remainder of the physical examination was normal. Urine toxicologic screening was positive for buprenorphine, norbuprenorphine, and norfentanyl; buprenorphine-naloxone therapy was resumed.
Three weeks before the current presentation, dark urine and light-headedness developed and did not improve with increased fluid consumption. The patient also noticed slow thinking and arthralgias in the hands, wrists, and elbows. He was evaluated by a new primary care provider. The temperature was 36.7[degrees]C, the pulse 53 beats per minute, and the blood pressure 104/66 mm Hg. The joints of the hands, wrists, and elbows were normal. The neurologic examination was normal, as was the remainder of the physical examination. Blood levels of electrolytes and glucose were normal, as were the complete blood count, differential count, and results of renal-function tests. Urinalysis revealed clear, dark-yellow urine, with a specific gravity of 1.020 (reference range, 1.00 to 1.030), a pH of 7.5 (reference range, 5.0 to 9.0), trace ketones (reference value, negative), and 2+ urobilinogen (reference value, negative). Other laboratory test results are shown in Table 1.	
Table 1 
One week before the current presentation, the patient noticed yellowing of the eyes and skin. One week later, he was seen by his primary care provider and was immediately transported by ambulance to the emergency department of this hospital for evaluation.
On evaluation, the patient reported 2 weeks of anorexia, malaise, nausea with dark-brown emesis, profuse nonbloody watery diarrhea, intermittent abdominal cramping, poor sleep, blurry vision, and episodes of forgetfulness and loss of concentration. He had no fevers, chills, bleeding, or pulmonary or genitourinary symptoms and had no sick contacts. There was a history of osteoarthritis, depression, and anxiety. HCV infection had been diagnosed but not treated while the patient was incarcerated. He reported that when he used intravenous heroin, he did not reuse, share, or lick needles. Allergies included penicillin, aspirin, and sulfonamide-containing antibiotic agents. The only medication was sublingual buprenorphine-naloxone.
The patient was divorced and had no children. He had not been sexually active in 2 years. He was born in the northeastern United States and had not traveled outside the country. Since his release from prison, he was unemployed, homeless, and sleeping in a shelter. He had no known exposure to rodents or rodent excreta. He smoked cigarettes daily and had done so for 20 years. He had previously consumed 2 liters of vodka daily but had quit 6 years earlier. His parents were deceased; he was estranged from his siblings, and their medical history was unknown.
On physical examination, the temperature was 36.3[degrees]C, the pulse 57 beats per minute, the blood pressure 113/72 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 68 kg. The patient appeared jaundiced and had marked scleral icterus. The mucous membranes were moist, and there was no cervical lymphadenopathy. The abdomen was soft and nondistended, with no evidence of ascites. There was mild tenderness on palpation of the upper right quadrant of the abdomen, with no hepatosplenomegaly. The patient had no gynecomastia, caput medusae, or spider angiomas. He was alert and fully oriented and had no asterixis. There was no rash or leg edema. The remainder of the physical examination was normal.
Blood levels of electrolytes, glucose, and lipase were normal, as were the complete blood count, differential count, and results of renal-function tests. Serum toxicologic screening did not detect acetaminophen, salicylates, tricyclics, or ethanol. Other laboratory test results are shown in Table 1.
Dr. Mark A. Anderson: Limited ultrasonography of the right upper quadrant (Figure 1) revealed no bile-duct dilatation, a patent main portal vein with hepatopetal flow, and normal hepatic parenchymal echotexture. Diffuse, hypoechoic gallbladder-wall thickening was present, without gallbladder distention, cholelithiasis, or pericholecystic fluid. Murphy's sign was negative. There was trace perihepatic ascites.	
Figure 1
Dr. Planer: Additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 55-year-old man with a history of opioid use disorder and hepatitis C virus (HCV) infection presented to this hospital with jaundice.
Four months before the current presentation, the patient was released from prison after a 2-year incarceration. After he left prison, he resumed injecting heroin and had three episodes of overdose. He was evaluated at another hospital for symptoms of depression and was admitted for psychiatric treatment. During that admission, sublingual buprenorphine-naloxone therapy was initiated, and the patient was discharged.
One day after discharge and 5 weeks before the current presentation, headache, body aches, sweats, diarrhea, and nausea developed. The patient presented to a clinic for substance use disorder that is affiliated with the other hospital and reported that he had been unable to obtain sublingual buprenorphine-naloxone from a pharmacy after discharge. The temperature was 36.6[degrees]C, the pulse 70 beats per minute, and the blood pressure 100/68 mm Hg. The weight was 72 kg. He appeared to be restless, but the remainder of the physical examination was normal. Urine toxicologic screening was positive for buprenorphine, norbuprenorphine, and norfentanyl; buprenorphine-naloxone therapy was resumed.
Three weeks before the current presentation, dark urine and light-headedness developed and did not improve with increased fluid consumption. The patient also noticed slow thinking and arthralgias in the hands, wrists, and elbows. He was evaluated by a new primary care provider. The temperature was 36.7[degrees]C, the pulse 53 beats per minute, and the blood pressure 104/66 mm Hg. The joints of the hands, wrists, and elbows were normal. The neurologic examination was normal, as was the remainder of the physical examination. Blood levels of electrolytes and glucose were normal, as were the complete blood count, differential count, and results of renal-function tests. Urinalysis revealed clear, dark-yellow urine, with a specific gravity of 1.020 (reference range, 1.00 to 1.030), a pH of 7.5 (reference range, 5.0 to 9.0), trace ketones (reference value, negative), and 2+ urobilinogen (reference value, negative). Other laboratory test results are shown in Table 1.	
Table 1 
One week before the current presentation, the patient noticed yellowing of the eyes and skin. One week later, he was seen by his primary care provider and was immediately transported by ambulance to the emergency department of this hospital for evaluation.
On evaluation, the patient reported 2 weeks of anorexia, malaise, nausea with dark-brown emesis, profuse nonbloody watery diarrhea, intermittent abdominal cramping, poor sleep, blurry vision, and episodes of forgetfulness and loss of concentration. He had no fevers, chills, bleeding, or pulmonary or genitourinary symptoms and had no sick contacts. There was a history of osteoarthritis, depression, and anxiety. HCV infection had been diagnosed but not treated while the patient was incarcerated. He reported that when he used intravenous heroin, he did not reuse, share, or lick needles. Allergies included penicillin, aspirin, and sulfonamide-containing antibiotic agents. The only medication was sublingual buprenorphine-naloxone.
The patient was divorced and had no children. He had not been sexually active in 2 years. He was born in the northeastern United States and had not traveled outside the country. Since his release from prison, he was unemployed, homeless, and sleeping in a shelter. He had no known exposure to rodents or rodent excreta. He smoked cigarettes daily and had done so for 20 years. He had previously consumed 2 liters of vodka daily but had quit 6 years earlier. His parents were deceased; he was estranged from his siblings, and their medical history was unknown.
On physical examination, the temperature was 36.3[degrees]C, the pulse 57 beats per minute, the blood pressure 113/72 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 68 kg. The patient appeared jaundiced and had marked scleral icterus. The mucous membranes were moist, and there was no cervical lymphadenopathy. The abdomen was soft and nondistended, with no evidence of ascites. There was mild tenderness on palpation of the upper right quadrant of the abdomen, with no hepatosplenomegaly. The patient had no gynecomastia, caput medusae, or spider angiomas. He was alert and fully oriented and had no asterixis. There was no rash or leg edema. The remainder of the physical examination was normal.
Blood levels of electrolytes, glucose, and lipase were normal, as were the complete blood count, differential count, and results of renal-function tests. Serum toxicologic screening did not detect acetaminophen, salicylates, tricyclics, or ethanol. Other laboratory test results are shown in Table 1.
Dr. Mark A. Anderson: Limited ultrasonography of the right upper quadrant (Figure 1) revealed no bile-duct dilatation, a patent main portal vein with hepatopetal flow, and normal hepatic parenchymal echotexture. Diffuse, hypoechoic gallbladder-wall thickening was present, without gallbladder distention, cholelithiasis, or pericholecystic fluid. Murphy's sign was negative. There was trace perihepatic ascites.	
Figure 1
Dr. Planer: Additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of opioid use disorder and hepatitis C virus (HCV) infection. He presents with jaundice, dark urine, yellowing of the eyes and skin, anorexia, malaise, nausea with dark-brown emesis, profuse nonbloody watery diarrhea, intermittent abdominal cramping, poor sleep, blurry vision, and episodes of forgetfulness and loss of concentration. These symptoms are consistent with acute hepatitis. Given his history of HCV infection, it is likely that his symptoms are due to a flare-up of his chronic HCV infection, possibly due to his resumed heroin use after his release from prison.\n\nAcute Hepatitis C infection.""
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        ""content"": ""The patient has a history of opioid use disorder and hepatitis C virus (HCV) infection. He presents with jaundice, dark urine, light-headedness, slow thinking, and arthralgias. His urinalysis revealed clear, dark-yellow urine, with a specific gravity of 1.020, a pH of 7.5, trace ketones, and 2+ urobilinogen. He also reported 2 weeks of anorexia, malaise, nausea with dark-brown emesis, profuse nonbloody watery diarrhea, intermittent abdominal cramping, poor sleep, blurry vision, and episodes of forgetfulness and loss of concentration. His physical examination revealed jaundice and marked scleral icterus. Ultrasonography of the right upper quadrant revealed no bile-duct dilatation, a patent main portal vein with hepatopetal flow, and normal hepatic parenchymal echotexture. Diffuse, hypoechoic gallbladder-wall thickening was present, without gallbladder distention, cholelithiasis, or pericholecystic fluid. There was trace perihepatic ascites. These symptoms and findings suggest acute hepatitis, likely due to his known HCV infection.\n\nDiagnosis: Acute Hepatitis C.""
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10.1056/NEJMcpc1900421,Case 14-2019: A 44-Year-Old Man with Neck Pain and Swelling,,Metastatic postpubertal immature teratoma.,,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 44-year-old right-handed man was admitted to the cardiology unit of this hospital because of pain and swelling on the left side of the neck.
Twelve weeks earlier, at this hospital, the patient had undergone uncomplicated placement of an implantable cardioverter-defibrillator (ICD) through the left cephalic vein (Figure 1). Immediately after implantation, he began to have a transient sensation of ""pins and needles"" in the left hand; he previously had had similar, work-related tingling and decreased sensation in the ulnar-nerve distribution of the left arm. Neurologic examination was normal. A chest radiograph showed that the ICD leads were in the appropriate positions (Figure 2A). Three weeks after implantation, routine interrogation of the ICD was normal.	
Figure 1 
Five weeks after implantation, the patient awoke with a headache and neck pain on the left side. He initially attributed the pain to his sleeping position, but it continued throughout the day. When numbness and tingling developed in the left fingertips, along with shooting pains in the left arm and toes, he presented to another hospital and was admitted for further evaluation.
Dr. Dexter P. Mendoza: At the other hospital, imaging studies were obtained. A computed tomographic (CT) scan of the head, obtained without the administration of intravenous contrast material, was normal. CT angiography of the chest and abdomen ruled out pulmonary embolism and aortic dissection but revealed a partially visible mass in the left supraclavicular region (Figure 2B). Ultrasonography of the neck revealed a complex mass, measuring 4.3 cm in diameter, without internal Doppler flow (Figure 2C). These findings were thought to be most consistent with a hematoma.
Dr. Dudzinski: Numbness and tingling in the left arm increased in intensity, and the next morning, the patient was transferred to the cardiology unit of this hospital, where he was evaluated by the neurology and vascular surgery services. Examination was notable for tenderness and firmness in the left supraclavicular fossa, without erythema or drainage, and mildly diminished pinprick sensation along the lateral dorsum of the left hand and the ophthalmic and maxillary branches of the left trigeminal nerve.
Dr. Mendoza: Repeat ultrasonography of the neck and supraclavicular fossa on the left side revealed a heterogeneously hypoechoic lesion, measuring 4.5 cm in diameter, that was suggestive of an evolving hematoma.
Dr. Dudzinski: Ultrasonographically guided needle aspiration revealed 5 ml of thin, brown fluid that was suggestive of old blood, with 104,500 white cells per cubic millimeter, of which 79% were neutrophils. Gram's staining revealed few neutrophils and mononuclear cells and no organisms. An acid-fast stain for mycobacteria was negative, and microbiologic cultures were performed. Clopidogrel was stopped, and the dose of aspirin was increased. The patient was discharged after 2 days. He received a 7-day course of cephalexin, a tapering course of gabapentin, and oxycodone to be taken as needed. He was advised to avoid lifting his arm above his head.
Two weeks after discharge, at the electrophysiology clinic of this hospital, the patient reported that the neck swelling had greatly reduced but residual numbness was present in the tips of the left third, fourth, and fifth digits. Five days after the evaluation in the electrophysiology clinic, he returned to the emergency department of this hospital for recurrent swelling and pain in the neck and supraclavicular region on the left side; numbness and tingling in the face, shoulder, and arm on the left side; mild dysphagia; and a feeling that his face was hotter on the left side than on the right side. Residual numbness in the tips of the left third, fourth, and fifth digits persisted. Examination was notable for reduced sensation in the left trigeminal-nerve distribution and dysesthesia in the trigeminal-nerve distribution and left arm.
The patient was admitted to the cardiology unit. The hemoglobin level was 11.4 g per deciliter (normal range, 13.5 to 17.5), and the hematocrit 32.3% (normal range, 41 to 53). All other blood test results, including the troponin T level and results of liver-function tests, were normal, as was urinalysis. Specimens of blood were obtained for culture, and additional imaging studies were performed.
Dr. Mendoza: Ultrasonography again revealed a heterogeneously hypoechoic lesion, measuring 3.9 cm in diameter, in the left supraclavicular region; the left internal jugular, subclavian, axillary, brachial, and basilic veins were patent. Contrast-enhanced CT of the neck revealed a heterogeneous mass, measuring 4.0 cm in diameter, that was located in the soft tissue of the left side of the neck, deep to the sternocleidomastoid muscle and abutting the left common carotid artery and brachial plexus (Figure 2D). Small calcifications were noted in the mass. There was no evidence of arterial or venous obstruction.
Dr. Dudzinski: Needle aspiration of the mass was again performed and revealed 1.5 ml of thick red fluid that appeared to be consistent with blood. Gram's staining revealed abundant mononuclear cells and no neutrophils or organisms. Fluid aspirate was obtained for culture. Cephalexin and gabapentin were resumed, and the patient was discharged after 2 days.
Two weeks after discharge, in the electrophysiology clinic, the patient reported resolution of the pain in the neck and arm on the left side. He had numbness in only the left third, fourth, and fifth digits. Clopidogrel was resumed.
Two weeks later, neck swelling recurred. The patient had local, dull pain in the supraclavicular fossa that radiated toward the left ear and left trapezius muscle. He also began to have focal swelling on the left side of the face and throat fullness, without dyspnea, drooling, or dysphonia, and he sought evaluation at the emergency department of this hospital.
A review of systems was notable for sciatica and heartburn. The patient had no symptoms of heart failure or dysrhythmia, fever, chills, sweats, chest pain, weight loss, appetite change, rash, or pruritus. The medical history was notable for hypertension, dyslipidemia, and coronary artery disease with two anterior ST-segment elevation myocardial infarctions. The first, which had occurred 8 years before this admission, was treated with percutaneous coronary interventions and was complicated by acute in-stent thrombosis and later in-stent restenosis. The second, which had occurred 14 months before this admission in the presence of occlusion of the previously placed stents, was treated with intraaortic balloon counterpulsation and multivessel coronary-artery bypass grafting. The patient had resultant ischemic cardiomyopathy and progressive left ventricular systolic dysfunction, with a current left ventricular ejection fraction of 28%.
In addition, the patient had a history of asthma, for which he had had multiple intubations, tapering courses of glucocorticoids, and admissions to the intensive care unit. When he was 20 years of age, he had testicular cancer, for which he received treatment with orchiectomy and chemotherapy at another hospital. He also had a history of erosive esophagitis and depression. Medications included aspirin, clopidogrel, simvastatin, carvedilol, lisinopril, gabapentin, quetiapine, and omeprazole. Heparin had caused thrombocytopenia, and various statin drugs had caused myalgias.
There was no family history of coronary artery disease or cardiomyopathy. The patient's mother had hypertension and diabetes, and his father, brother, and two children were all healthy. He was disabled and had not worked since he had his first myocardial infarction. He smoked a half pack of cigarettes per day and had done so since he was 16 years of age, and he also smoked marijuana. He had a history of binge drinking, which had been complicated by pancreatitis, as well as a history of cocaine use, but he had been abstinent from both alcohol and cocaine for the previous 3 years.
On examination, the temperature was 36.7[degrees]C, the heart rate 81 beats per minute, the blood pressure 124/74 mm Hg in both arms, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The height was 170 cm, the weight 81.2 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 28.1. He was anxious and in mild discomfort. In the left supraclavicular fossa, there was a nontender, nonerythematous, nonmobile mass, measuring 6 cm by 4 cm, without overlying skin changes or a thrill or bruit. The deltopectoral incision was well healed. The jugular venous pulse on the right side was 5 cm of water with a normal contour, and both carotid pulses were 2+ without bruits. There was a systolic murmur (grade 1/6) at the left upper sternal border. Radial and ulnar pulses, strength, fine-motor coordination, and sensation to light touch and pinprick were symmetric in the left and right arms. The remainder of the examination was normal.
The hemoglobin level was 12.2 g per deciliter, the hematocrit 34.9%, and the plasma creatinine level 1.65 mg per deciliter (146 [mu]mol per liter; normal range, 0.6 to 1.5 mg per deciliter [53 to 133 [mu]mol per liter]). An electrocardiogram showed sinus rhythm, left atrial enlargement, and evidence of old anteroseptal and lateral myocardial infarctions, findings that were all unchanged from previous studies.
Dr. Mendoza: Ultrasonography of the left side of the neck revealed no substantial change in the complex mass in the left supraclavicular region. The carotid artery was patent, and there was no Doppler flow in the mass or evidence of pseudoaneurysm or arteriovenous fistula.
Dr. Dudzinski: The patient was admitted to the cardiology unit. Aspirin and clopidogrel were withheld, and normal saline was administered intravenously. On the second hospital day, transbrachial arteriography was performed to evaluate for a possible injury to subclavian vessels with delayed local bleeding. The subclavian arterial system was normal, without extravasation, but there was evidence of a blush in the area of the mass.
Additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 44-year-old right-handed man was admitted to the cardiology unit of this hospital because of pain and swelling on the left side of the neck.
Twelve weeks earlier, at this hospital, the patient had undergone uncomplicated placement of an implantable cardioverter-defibrillator (ICD) through the left cephalic vein (Figure 1). Immediately after implantation, he began to have a transient sensation of ""pins and needles"" in the left hand; he previously had had similar, work-related tingling and decreased sensation in the ulnar-nerve distribution of the left arm. Neurologic examination was normal. A chest radiograph showed that the ICD leads were in the appropriate positions (Figure 2A). Three weeks after implantation, routine interrogation of the ICD was normal.	
Figure 1 
Five weeks after implantation, the patient awoke with a headache and neck pain on the left side. He initially attributed the pain to his sleeping position, but it continued throughout the day. When numbness and tingling developed in the left fingertips, along with shooting pains in the left arm and toes, he presented to another hospital and was admitted for further evaluation.
Dr. Dexter P. Mendoza: At the other hospital, imaging studies were obtained. A computed tomographic (CT) scan of the head, obtained without the administration of intravenous contrast material, was normal. CT angiography of the chest and abdomen ruled out pulmonary embolism and aortic dissection but revealed a partially visible mass in the left supraclavicular region (Figure 2B). Ultrasonography of the neck revealed a complex mass, measuring 4.3 cm in diameter, without internal Doppler flow (Figure 2C). These findings were thought to be most consistent with a hematoma.
Dr. Dudzinski: Numbness and tingling in the left arm increased in intensity, and the next morning, the patient was transferred to the cardiology unit of this hospital, where he was evaluated by the neurology and vascular surgery services. Examination was notable for tenderness and firmness in the left supraclavicular fossa, without erythema or drainage, and mildly diminished pinprick sensation along the lateral dorsum of the left hand and the ophthalmic and maxillary branches of the left trigeminal nerve.
Dr. Mendoza: Repeat ultrasonography of the neck and supraclavicular fossa on the left side revealed a heterogeneously hypoechoic lesion, measuring 4.5 cm in diameter, that was suggestive of an evolving hematoma.
Dr. Dudzinski: Ultrasonographically guided needle aspiration revealed 5 ml of thin, brown fluid that was suggestive of old blood, with 104,500 white cells per cubic millimeter, of which 79% were neutrophils. Gram's staining revealed few neutrophils and mononuclear cells and no organisms. An acid-fast stain for mycobacteria was negative, and microbiologic cultures were performed. Clopidogrel was stopped, and the dose of aspirin was increased. The patient was discharged after 2 days. He received a 7-day course of cephalexin, a tapering course of gabapentin, and oxycodone to be taken as needed. He was advised to avoid lifting his arm above his head.
Two weeks after discharge, at the electrophysiology clinic of this hospital, the patient reported that the neck swelling had greatly reduced but residual numbness was present in the tips of the left third, fourth, and fifth digits. Five days after the evaluation in the electrophysiology clinic, he returned to the emergency department of this hospital for recurrent swelling and pain in the neck and supraclavicular region on the left side; numbness and tingling in the face, shoulder, and arm on the left side; mild dysphagia; and a feeling that his face was hotter on the left side than on the right side. Residual numbness in the tips of the left third, fourth, and fifth digits persisted. Examination was notable for reduced sensation in the left trigeminal-nerve distribution and dysesthesia in the trigeminal-nerve distribution and left arm.
The patient was admitted to the cardiology unit. The hemoglobin level was 11.4 g per deciliter (normal range, 13.5 to 17.5), and the hematocrit 32.3% (normal range, 41 to 53). All other blood test results, including the troponin T level and results of liver-function tests, were normal, as was urinalysis. Specimens of blood were obtained for culture, and additional imaging studies were performed.
Dr. Mendoza: Ultrasonography again revealed a heterogeneously hypoechoic lesion, measuring 3.9 cm in diameter, in the left supraclavicular region; the left internal jugular, subclavian, axillary, brachial, and basilic veins were patent. Contrast-enhanced CT of the neck revealed a heterogeneous mass, measuring 4.0 cm in diameter, that was located in the soft tissue of the left side of the neck, deep to the sternocleidomastoid muscle and abutting the left common carotid artery and brachial plexus (Figure 2D). Small calcifications were noted in the mass. There was no evidence of arterial or venous obstruction.
Dr. Dudzinski: Needle aspiration of the mass was again performed and revealed 1.5 ml of thick red fluid that appeared to be consistent with blood. Gram's staining revealed abundant mononuclear cells and no neutrophils or organisms. Fluid aspirate was obtained for culture. Cephalexin and gabapentin were resumed, and the patient was discharged after 2 days.
Two weeks after discharge, in the electrophysiology clinic, the patient reported resolution of the pain in the neck and arm on the left side. He had numbness in only the left third, fourth, and fifth digits. Clopidogrel was resumed.
Two weeks later, neck swelling recurred. The patient had local, dull pain in the supraclavicular fossa that radiated toward the left ear and left trapezius muscle. He also began to have focal swelling on the left side of the face and throat fullness, without dyspnea, drooling, or dysphonia, and he sought evaluation at the emergency department of this hospital.
A review of systems was notable for sciatica and heartburn. The patient had no symptoms of heart failure or dysrhythmia, fever, chills, sweats, chest pain, weight loss, appetite change, rash, or pruritus. The medical history was notable for hypertension, dyslipidemia, and coronary artery disease with two anterior ST-segment elevation myocardial infarctions. The first, which had occurred 8 years before this admission, was treated with percutaneous coronary interventions and was complicated by acute in-stent thrombosis and later in-stent restenosis. The second, which had occurred 14 months before this admission in the presence of occlusion of the previously placed stents, was treated with intraaortic balloon counterpulsation and multivessel coronary-artery bypass grafting. The patient had resultant ischemic cardiomyopathy and progressive left ventricular systolic dysfunction, with a current left ventricular ejection fraction of 28%.
In addition, the patient had a history of asthma, for which he had had multiple intubations, tapering courses of glucocorticoids, and admissions to the intensive care unit. When he was 20 years of age, he had testicular cancer, for which he received treatment with orchiectomy and chemotherapy at another hospital. He also had a history of erosive esophagitis and depression. Medications included aspirin, clopidogrel, simvastatin, carvedilol, lisinopril, gabapentin, quetiapine, and omeprazole. Heparin had caused thrombocytopenia, and various statin drugs had caused myalgias.
There was no family history of coronary artery disease or cardiomyopathy. The patient's mother had hypertension and diabetes, and his father, brother, and two children were all healthy. He was disabled and had not worked since he had his first myocardial infarction. He smoked a half pack of cigarettes per day and had done so since he was 16 years of age, and he also smoked marijuana. He had a history of binge drinking, which had been complicated by pancreatitis, as well as a history of cocaine use, but he had been abstinent from both alcohol and cocaine for the previous 3 years.
On examination, the temperature was 36.7[degrees]C, the heart rate 81 beats per minute, the blood pressure 124/74 mm Hg in both arms, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The height was 170 cm, the weight 81.2 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 28.1. He was anxious and in mild discomfort. In the left supraclavicular fossa, there was a nontender, nonerythematous, nonmobile mass, measuring 6 cm by 4 cm, without overlying skin changes or a thrill or bruit. The deltopectoral incision was well healed. The jugular venous pulse on the right side was 5 cm of water with a normal contour, and both carotid pulses were 2+ without bruits. There was a systolic murmur (grade 1/6) at the left upper sternal border. Radial and ulnar pulses, strength, fine-motor coordination, and sensation to light touch and pinprick were symmetric in the left and right arms. The remainder of the examination was normal.
The hemoglobin level was 12.2 g per deciliter, the hematocrit 34.9%, and the plasma creatinine level 1.65 mg per deciliter (146 [mu]mol per liter; normal range, 0.6 to 1.5 mg per deciliter [53 to 133 [mu]mol per liter]). An electrocardiogram showed sinus rhythm, left atrial enlargement, and evidence of old anteroseptal and lateral myocardial infarctions, findings that were all unchanged from previous studies.
Dr. Mendoza: Ultrasonography of the left side of the neck revealed no substantial change in the complex mass in the left supraclavicular region. The carotid artery was patent, and there was no Doppler flow in the mass or evidence of pseudoaneurysm or arteriovenous fistula.
Dr. Dudzinski: The patient was admitted to the cardiology unit. Aspirin and clopidogrel were withheld, and normal saline was administered intravenously. On the second hospital day, transbrachial arteriography was performed to evaluate for a possible injury to subclavian vessels with delayed local bleeding. The subclavian arterial system was normal, without extravasation, but there was evidence of a blush in the area of the mass.
Additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of pain and swelling in the neck, along with the imaging findings of a mass in the left supraclavicular region, suggest a hematoma or other type of mass. The fact that the patient had recently undergone placement of an implantable cardioverter-defibrillator (ICD) through the left cephalic vein suggests that the mass could be related to this procedure. The patient's symptoms of numbness and tingling in the left arm and hand, along with shooting pains in the left arm and toes, suggest a neurological issue, possibly related to the mass pressing on nerves in the neck. The fact that the mass was not responsive to antibiotics and did not show any signs of infection on Gram stain or culture suggests that it is not an abscess or other type of infectious mass. The fact that the mass was found to contain old blood suggests that it is a hematoma. The fact that the mass recurred after initial treatment suggests that it is not simply a post-operative hematoma, but may be related to a vascular issue such as a pseudoaneurysm or arteriovenous fistula. The fact that the mass was found to be abutting the left common carotid artery and brachial plexus on CT scan supports this idea. The fact that the patient's symptoms improved after stopping clopidogrel, a blood thinner, also supports the idea that the mass is related to a vascular issue. The fact that the patient's symptoms recurred after clopidogrel was resumed further supports this idea. The fact that arteriography showed a blush in the area of the mass suggests that there is abnormal blood flow in the area, possibly due to a pseudoaneurysm or arteriovenous fistula.\n\nDiagnosis: Pseudoaneurysm or arteriovenous fistula related to ICD placement.""
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        ""content"": ""The patient's symptoms began after the placement of an implantable cardioverter-defibrillator (ICD) through the left cephalic vein. He experienced pain, swelling, and numbness in the left side of his neck and arm. Imaging studies revealed a mass in the left supraclavicular region, which was initially thought to be a hematoma. However, the mass did not resolve and instead fluctuated in size, causing recurrent symptoms. The mass was aspirated multiple times, revealing fluid suggestive of old blood and no evidence of infection. The patient's symptoms and the characteristics of the mass suggest a pseudoaneurysm, which can occur as a complication of vascular procedures such as the placement of an ICD. A pseudoaneurysm occurs when blood leaks from a damaged blood vessel and collects in the surrounding tissue, forming a mass. This diagnosis is further supported by the evidence of a blush in the area of the mass seen on arteriography, which is consistent with a pseudoaneurysm.\n\nDiagnosis: Pseudoaneurysm.""
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        ""content"": ""The patient is a 44-year-old man with a history of coronary artery disease, hypertension, dyslipidemia, and testicular cancer. He presents with recurrent pain and swelling in the left side of the neck, which started after the placement of an implantable cardioverter-defibrillator (ICD) through the left cephalic vein. The differential diagnosis for this patient includes hematoma, infection, thrombosis, and malignancy. The patient's symptoms of numbness and tingling in the left arm and fingers, as well as shooting pains in the left arm and toes, could be due to nerve compression from the swelling. The CT scan and ultrasound of the neck revealed a mass in the left supraclavicular region, which was initially thought to be a hematoma. However, the persistence of the mass and the patient's symptoms despite treatment suggest that this may not be the case. The patient's history of testicular cancer raises the possibility of a malignancy, although the location of the mass and the absence of other systemic symptoms make this less likely. The patient's history of ICD placement and the location of the mass suggest the possibility of an infection or thrombosis related to the device. However, the fluid aspirated from the mass did not show any organisms, and the patient's symptoms did not improve with antibiotics, making an infection less likely. The presence of a \""blush\"" in the area of the mass on arteriography suggests the possibility of a vascular lesion, such as a pseudoaneurysm or arteriovenous fistula. However, the ultrasound did not show any Doppler flow in the mass, making this less likely. Given the patient's history and the results of the diagnostic tests, the most likely diagnosis is a hematoma related to the ICD placement that has not resolved.\n\nDiagnosis: Unresolved hematoma related to ICD placement.""
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10.1056/NEJMcpc1900591,Case 13-2019: A 54-Year-Old Man with Alcohol Withdrawal and Altered Mental Status,"Hemoglobin (g/dl)   15.9 13.3 15.6 15.6
Hematocrit (%)   47.4 39.1 45.4 44.7
White-cell count (per mm3)   8390 8720 11,070 15,430
Differential count (%)
Neutrophils   75.4 63.5 66.4 81.9
Lymphocytes   14.1 21.2 22.5 12.6
Monocytes   8.2 12.6 7.2 3.6
Eosinophils   0.5 1.4 1.1 0.1
Basophils   0.7 0.8 1.1 0.5
Immature granulocytes   1.1 0.5 1.7 1.3
Platelet count (per mm3
)   504,000 360,000 436,000 508,000
Mean corpuscular volume (fl)   80.2 79.8 78.1 76.1
Sodium (mmol/liter)   138 140 139 140
Potassium (mmol/liter)   3.7 3.6 3.5 3.5
Chloride (mmol/liter)   98 102 101 104
Carbon dioxide (mmol/liter)   19 22 18 22
Urea nitrogen (mg/dl)   17 13 14 12
Creatinine (mg/dl)   0.93 0.66 1.24 1.15
Glucose (mg/dl)   243 143 139 148
Calcium (mg/dl)   9.4 8.6 9.3 9.1
Lactate (mmol/liter)   5.1 1.3 1.7 2.4
Ethanol (mg/dl) Negative 136 Negative
Protein (g/dl)
Total 6. .3 8.4 7.6 7.8
Albumin   4.1 4.1 4.3
Alanine aminotransferase (U/liter)   30 47 38
Aspartate aminotransferase (U/liter)   33 33 20
Alkaline phosphatase (U/liter)   134 140 126
Bilirubin (mg/dl)
Total  0.3 0.2 0.2
Direct 0.  <0.2 <0.2 <0.2
Creatine kinase (U/liter)   67 31                                                                          Prolactin (ng/ml) 0.1–15.2 20.6 39.6 28.5
Lipase (U/liter) 13–60 76
Phosphorus (mg/dl)   1.7 2.8
Magnesium (mg/dl)   1.7 1.7
Beta-hydroxybutyrate (mmol/liter) <0.4 0.1
Acetaminophen (μg/dl) 0. 5.0 <5.0
Salicylates (mg/dl) 0. 0.0 <0.3
Tricyclic antidepressants Negative Negative
Arterial blood gas
Fraction of inspired oxygen ‡
pH   7.40
Partial pressure of carbon dioxide 
(mm Hg)
  32
Partial pressure of oxygen (mm Hg)   121
High-sensitivity troponin T (ng/liter)   <6
Ammonia (μmol/liter) 12–48 46
Venous blood gas
pH   7.45
Partial pressure of carbon dioxide 
(mm Hg)
  31
Partial pressure of oxygen (mm Hg)   148
Routine urine toxicology screening Negative for amphetamines, 
barbiturates, 
cannabinoids, 
cocaine, and 
opiates
Negative Positive for barbiturates; negative 
for amphetamines, cannabinoids, cocaine, 
and opiates
Specific urine toxicology screening 
for drugs of abuse
Negative for 6-monoacetylmorphine, 
buprenorphine, 
methadone, and 
oxycodone
Negative",Surreptitious ingestion of isopropyl alcohol.,Isopropanol ingestion with possible coingestion of benzoic acid (mouthwash).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 54-year-old man was evaluated for acute altered mental status after being hospitalized for alcohol withdrawal.
The patient was homeless but had recently been enrolled in an addiction treatment program in a residential clinical stabilization service. He reportedly left the program 4 days before admission to this hospital and then ""blacked out"" daily in tandem with drinking 0.5 to 1 gallon of vodka throughout the day. On the evening before admission, he decided to stop drinking alcohol. Approximately 10 hours later, he awoke on the ground without recollection of lying down; he had had vivid dreams and tremulousness and was worried that he may have had a seizure. He presented to the emergency department of this hospital.
The patient reported diffuse headache, nausea, nonbloody and nonbilious emesis, restlessness, auditory hallucinations, and a sensation of insects crawling on the skin. A review of systems was notable for heartburn and was negative for confusion, ataxia, dizziness, focal weakness and numbness, tongue laceration, incontinence, visual hallucinations, fever, chills, dyspnea, chest pain, abdominal pain, diarrhea, and dysuria. His medical history was notable for seizure disorder in childhood, hypertension, and glaucoma, and he had undergone umbilical hernia repair. He reported that he was taking gabapentin and hydroxyzine and had no adverse drug reactions. The patient had a lengthy history of alcohol use, with associated delirium tremens and withdrawal seizures, although he had abstained from alcohol use over a 7-year period, which coincided with incarceration and ended 8 years before admission. He smoked cigarettes and had smoked 0.5 to 1 pack daily since he was 18 years of age. He had previously used marijuana, hash oil, and lysergic acid diethylamide. His family history was notable for alcohol use disorder in his parents and two brothers.
On examination, the temperature was 36.7[degrees]C, the heart rate 108 beats per minute, the blood pressure 161/96 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 55.4 kg, the height 142 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 27.5. The patient was described as restless, anxious, and flushed. Tongue fasciculations and mild arm tremors were present. There was no tenderness on the head, face, or spine. Auscultation revealed a tachycardic rhythm and scattered wheezes. There were reducible ventral and umbilical hernias, with a well-healed umbilical scar. The remainder of the examination was normal.
Levels of globulin and thyrotropin were normal; other laboratory test results are shown in Table 1. Urinalysis revealed slightly cloudy urine with trace ketones but was otherwise normal. Samples of the blood and urine were obtained for culture. An electrocardiogram was notable for sinus tachycardia and borderline left atrial enlargement. A chest radiograph was normal, and a computed tomographic (CT) scan of the head, obtained without the administration of contrast material, showed no intracranial hemorrhage, mass, or stroke.	
Table 1 
Folate, multivitamins, intravenous normal saline, thiamine, and lorazepam were administered during the next 10 hours. Additional laboratory test results are shown in Table 1. Urinalysis was normal. The patient was admitted to the hospital.
Phenobarbital was administered at a gradually tapering dose for management of alcohol withdrawal. The patient was evaluated by the addiction consultation service; he reported ongoing alcohol cravings, for which topiramate was recommended. Tremors, hallucinosis, and tachycardia all abated with phenobarbital treatment, but cravings persisted. He awaited transfer to an alcohol detoxification facility.
On hospital day 5, the patient reported feeling anxious. That evening, a nurse found him to be acutely delirious, lethargic, and minimally responsive, even to sternal rub, just 1 hour after he had been awake and conversing; he had not left his room. A fingerstick glucose measurement was 151 mg per deciliter (8.4 mmol per liter). Examination revealed tachycardia with a heart rate of 107 beats per minute (as compared with 78 beats per minute 6 hours previously), tachypnea with a respiratory rate of 30 breaths per minute, an oxygen saturation of 95% while he was receiving oxygen through a nasal cannula at a rate of 2 liters per minute, and new abdominal distention without tenderness; he had no tremors, seizure, incontinence, or tongue trauma. Naloxone was administered but had no effect. An electrocardiogram showed sinus tachycardia. Results of repeat laboratory tests are shown in Table 1. Urinalysis was again normal. A chest radiograph was normal, as was a CT scan of the head that was obtained without the administration of contrast material.
The neurology service evaluated the patient. The next morning, the patient was more awake, alert to person and place, and responsive to commands. An electroencephalogram showed generalized theta slowing, without epileptiform abnormalities. Later in the day, he was lethargic. He reported heartburn and nausea and vomited dark-brown material. Examination revealed abdominal distention and guaiac-positive, black stool. Laboratory test results are shown in Table 1. Urinalysis revealed trace ketones but was otherwise normal. Additional imaging studies were obtained.
Dr. Amirkasra Mojtahed: A CT scan of the abdomen and pelvis (Figure 1), obtained after the administration of oral and intravenous contrast material, showed multiple dilated small-bowel loops, with an associated segment of small-bowel wall thickening, but no changes consistent with bowel obstruction.	
Figure 1
Dr. Kearney: The surgery service evaluated the patient. A nasogastric tube was placed, with immediate return of 400 ml of dark-brown and ""coffee grounds"" material. Intravenous normal saline, vancomycin, cefepime, and metronidazole were administered.
Additional diagnostic test results were received
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 54-year-old man was evaluated for acute altered mental status after being hospitalized for alcohol withdrawal.
The patient was homeless but had recently been enrolled in an addiction treatment program in a residential clinical stabilization service. He reportedly left the program 4 days before admission to this hospital and then ""blacked out"" daily in tandem with drinking 0.5 to 1 gallon of vodka throughout the day. On the evening before admission, he decided to stop drinking alcohol. Approximately 10 hours later, he awoke on the ground without recollection of lying down; he had had vivid dreams and tremulousness and was worried that he may have had a seizure. He presented to the emergency department of this hospital.
The patient reported diffuse headache, nausea, nonbloody and nonbilious emesis, restlessness, auditory hallucinations, and a sensation of insects crawling on the skin. A review of systems was notable for heartburn and was negative for confusion, ataxia, dizziness, focal weakness and numbness, tongue laceration, incontinence, visual hallucinations, fever, chills, dyspnea, chest pain, abdominal pain, diarrhea, and dysuria. His medical history was notable for seizure disorder in childhood, hypertension, and glaucoma, and he had undergone umbilical hernia repair. He reported that he was taking gabapentin and hydroxyzine and had no adverse drug reactions. The patient had a lengthy history of alcohol use, with associated delirium tremens and withdrawal seizures, although he had abstained from alcohol use over a 7-year period, which coincided with incarceration and ended 8 years before admission. He smoked cigarettes and had smoked 0.5 to 1 pack daily since he was 18 years of age. He had previously used marijuana, hash oil, and lysergic acid diethylamide. His family history was notable for alcohol use disorder in his parents and two brothers.
On examination, the temperature was 36.7[degrees]C, the heart rate 108 beats per minute, the blood pressure 161/96 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 55.4 kg, the height 142 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 27.5. The patient was described as restless, anxious, and flushed. Tongue fasciculations and mild arm tremors were present. There was no tenderness on the head, face, or spine. Auscultation revealed a tachycardic rhythm and scattered wheezes. There were reducible ventral and umbilical hernias, with a well-healed umbilical scar. The remainder of the examination was normal.
Levels of globulin and thyrotropin were normal; other laboratory test results are shown in Table 1. Urinalysis revealed slightly cloudy urine with trace ketones but was otherwise normal. Samples of the blood and urine were obtained for culture. An electrocardiogram was notable for sinus tachycardia and borderline left atrial enlargement. A chest radiograph was normal, and a computed tomographic (CT) scan of the head, obtained without the administration of contrast material, showed no intracranial hemorrhage, mass, or stroke.	
Table 1 
Folate, multivitamins, intravenous normal saline, thiamine, and lorazepam were administered during the next 10 hours. Additional laboratory test results are shown in Table 1. Urinalysis was normal. The patient was admitted to the hospital.
Phenobarbital was administered at a gradually tapering dose for management of alcohol withdrawal. The patient was evaluated by the addiction consultation service; he reported ongoing alcohol cravings, for which topiramate was recommended. Tremors, hallucinosis, and tachycardia all abated with phenobarbital treatment, but cravings persisted. He awaited transfer to an alcohol detoxification facility.
On hospital day 5, the patient reported feeling anxious. That evening, a nurse found him to be acutely delirious, lethargic, and minimally responsive, even to sternal rub, just 1 hour after he had been awake and conversing; he had not left his room. A fingerstick glucose measurement was 151 mg per deciliter (8.4 mmol per liter). Examination revealed tachycardia with a heart rate of 107 beats per minute (as compared with 78 beats per minute 6 hours previously), tachypnea with a respiratory rate of 30 breaths per minute, an oxygen saturation of 95% while he was receiving oxygen through a nasal cannula at a rate of 2 liters per minute, and new abdominal distention without tenderness; he had no tremors, seizure, incontinence, or tongue trauma. Naloxone was administered but had no effect. An electrocardiogram showed sinus tachycardia. Results of repeat laboratory tests are shown in Table 1. Urinalysis was again normal. A chest radiograph was normal, as was a CT scan of the head that was obtained without the administration of contrast material.
The neurology service evaluated the patient. The next morning, the patient was more awake, alert to person and place, and responsive to commands. An electroencephalogram showed generalized theta slowing, without epileptiform abnormalities. Later in the day, he was lethargic. He reported heartburn and nausea and vomited dark-brown material. Examination revealed abdominal distention and guaiac-positive, black stool. Laboratory test results are shown in Table 1. Urinalysis revealed trace ketones but was otherwise normal. Additional imaging studies were obtained.
Dr. Amirkasra Mojtahed: A CT scan of the abdomen and pelvis (Figure 1), obtained after the administration of oral and intravenous contrast material, showed multiple dilated small-bowel loops, with an associated segment of small-bowel wall thickening, but no changes consistent with bowel obstruction.	
Figure 1
Dr. Kearney: The surgery service evaluated the patient. A nasogastric tube was placed, with immediate return of 400 ml of dark-brown and ""coffee grounds"" material. Intravenous normal saline, vancomycin, cefepime, and metronidazole were administered.
Additional diagnostic test results were received
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Wernicke's Encephalopathy. The patient's history of chronic alcohol abuse, combined with his symptoms of altered mental status, hallucinations, and tremors, suggest a diagnosis of Wernicke's encephalopathy. This condition is caused by thiamine deficiency, which is common in individuals with chronic alcoholism. The patient's symptoms improved with thiamine administration, further supporting this diagnosis.""
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        ""content"": ""The patient is a 54-year-old man with a history of alcohol use disorder who was admitted for alcohol withdrawal. He developed acute altered mental status on hospital day 5. The differential diagnosis for his altered mental status includes alcohol withdrawal, Wernicke's encephalopathy, delirium tremens, sepsis, and metabolic abnormalities such as electrolyte disturbances or hypoglycemia. However, his symptoms improved with phenobarbital treatment, making alcohol withdrawal less likely. His thiamine levels were normal, making Wernicke's encephalopathy less likely. He did not have a fever or leukocytosis, making sepsis less likely. His electrolyte levels and glucose were within normal limits, making metabolic abnormalities less likely. On hospital day 5, he developed acute delirium, lethargy, tachycardia, tachypnea, and abdominal distention. His stool was guaiac-positive and black, suggesting gastrointestinal bleeding. A CT scan of the abdomen and pelvis showed multiple dilated small-bowel loops and small-bowel wall thickening. These findings suggest a diagnosis of acute gastrointestinal bleeding, likely due to peptic ulcer disease or esophageal varices, both of which are common in patients with chronic alcohol use.\n\nDiagnosis: Acute gastrointestinal bleeding due to peptic ulcer disease or esophageal varices.""
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10.1056/NEJMcpc1900141,Case 12-2019: A 60-Year-Old Man with Weakness and Difficulty Chewing,,"Motor neuron disease with TAR DNA-binding protein 43 proteinopathy.
Amyotrophic lateral sclerosis.
Acute bronchopneumonia",Amyotrophic lateral sclerosis,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 60-year-old man was evaluated in the neurology clinic of this hospital because of weakness and difficulty chewing.
Six months before this presentation, weakness developed in the muscles of the patient's shoulders and arms, and he found it difficult to carry objects. He also noticed cramps in the muscles of his chest and shoulders.
Four months before this presentation, the patient began to have difficulty chewing food. He described mild difficulty chewing at the beginning of a meal, with the severity increasing during the meal.
The weakness and difficulty chewing persisted, and 5 weeks before this presentation, the patient was evaluated in a neurology clinic at another hospital. He reported excess salivation, slurred speech, mild constipation, and a weight loss of 3.6 kg over a period of 3 months. He had no associated pain, numbness, shortness of breath, memory deficits, or changes in bladder function or mood. Chronic diplopia had developed approximately 30 years earlier, after the patient had undergone surgery for correction of a retinal detachment; the diplopia was unchanged and improved with covering either eye.
On examination, the patient's speech was fluent, without dysarthria. There was no ophthalmoplegia or ptosis initially or with prolonged gaze. Results of formal testing of facial muscle power and jaw strength were normal. Motor testing revealed full, symmetric strength in the arms and legs, except for the strength on shoulder abduction and elbow flexion bilaterally, which was 4+ out of 5. Atrophy and fasciculations of the deltoid muscles were noted. Deep-tendon reflexes were 3+ and symmetric in the arms. Blood levels of electrolytes, glucose, vitamin B12 (cobalamin), copper, zinc, mercury, and arsenic were normal, as were results of tests of kidney, liver, and thyroid function. The complete blood count, erythrocyte-sedimentation rate, and creatine kinase level were normal. Screening tests for Lyme and syphilis antibodies were negative, as were tests for acetylcholine receptor binding, modulating, and blocking antibodies and antibodies to muscle-specific tyrosine kinase.
Computed tomography (CT) of the chest, performed after the intravenous administration of contrast material, was negative. Magnetic resonance imaging (MRI) of the head was performed without the administration of contrast material; T2-weighted images showed nonspecific, minimal, bilateral white-matter disease, a finding consistent with chronic small-vessel ischemic disease. MRI of the cervical spine revealed a normal cervical spinal cord and mild cervical spondylosis. Therapy with pyridostigmine was initiated, and the patient was referred to this hospital for further evaluation.
On presentation to this hospital, the patient reported that pyridostigmine had had no effect on his weakness or chronic diplopia but that his difficulty chewing had improved. However, 5 weeks after the initiation of treatment, the difficulty chewing had worsened despite continued therapy with pyridostigmine. The patient reported new weakness in the legs, with difficulty rising from a seated position. He also reported increasing frequency of the fasciculations and one fall at home. He had a history of hypertension, treated Lyme disease, psoriasis, and a traumatic compression fracture of the thoracic spine. Surgeries included cataract extractions and correction of a retinal detachment. He had no known allergies. Medications included pyridostigmine, hydrochlorothiazide, irbesartan, zolpidem, a multivitamin, and topical calcipotriene. He drank two alcoholic beverages weekly and did not smoke tobacco or use illicit drugs. There was no family history of neurologic disease.
On examination at this hospital, the temperature was 36.4[degrees]C, the blood pressure 146/82 mm Hg, the pulse 66 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 22.7. The patient's mental status was normal. Cranial-nerve testing revealed exophoria with upgaze that was present in both eyes but was most prominent on the right side. There was slightly reduced and slowed elevation of the eyebrows and mild weakness on eye closure and cheek inflation. Tongue movements were quick but weak with attempted opposition in the cheek. Lingual dysarthria was observed.
There was reduced bulk of the temporalis, periscapular, pectoralis, quadriceps, and intrinsic hand muscles. Diffuse fasciculations were observed in the face, tongue, trunk, quadriceps, and arms. Some fasciculations were forceful enough to result in movement of the fingers. Mild weakness was noted in the intrinsic hand muscles and proximal muscles of the arms and legs. Deep-tendon reflexes were asymmetrically brisk in the arms and normal in the legs. The plantar responses were flexor. Sensation, coordination, and gait were normal. Gynecomastia was present. The remainder of the examination was normal. The creatine kinase level was 498 U per liter (reference range, 60 to 400), and results of serum protein electrophoresis were normal. Serum testing for human immunodeficiency virus types 1 and 2 antibodies and p24 antigen was negative.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 60-year-old man was evaluated in the neurology clinic of this hospital because of weakness and difficulty chewing.
Six months before this presentation, weakness developed in the muscles of the patient's shoulders and arms, and he found it difficult to carry objects. He also noticed cramps in the muscles of his chest and shoulders.
Four months before this presentation, the patient began to have difficulty chewing food. He described mild difficulty chewing at the beginning of a meal, with the severity increasing during the meal.
The weakness and difficulty chewing persisted, and 5 weeks before this presentation, the patient was evaluated in a neurology clinic at another hospital. He reported excess salivation, slurred speech, mild constipation, and a weight loss of 3.6 kg over a period of 3 months. He had no associated pain, numbness, shortness of breath, memory deficits, or changes in bladder function or mood. Chronic diplopia had developed approximately 30 years earlier, after the patient had undergone surgery for correction of a retinal detachment; the diplopia was unchanged and improved with covering either eye.
On examination, the patient's speech was fluent, without dysarthria. There was no ophthalmoplegia or ptosis initially or with prolonged gaze. Results of formal testing of facial muscle power and jaw strength were normal. Motor testing revealed full, symmetric strength in the arms and legs, except for the strength on shoulder abduction and elbow flexion bilaterally, which was 4+ out of 5. Atrophy and fasciculations of the deltoid muscles were noted. Deep-tendon reflexes were 3+ and symmetric in the arms. Blood levels of electrolytes, glucose, vitamin B12 (cobalamin), copper, zinc, mercury, and arsenic were normal, as were results of tests of kidney, liver, and thyroid function. The complete blood count, erythrocyte-sedimentation rate, and creatine kinase level were normal. Screening tests for Lyme and syphilis antibodies were negative, as were tests for acetylcholine receptor binding, modulating, and blocking antibodies and antibodies to muscle-specific tyrosine kinase.
Computed tomography (CT) of the chest, performed after the intravenous administration of contrast material, was negative. Magnetic resonance imaging (MRI) of the head was performed without the administration of contrast material; T2-weighted images showed nonspecific, minimal, bilateral white-matter disease, a finding consistent with chronic small-vessel ischemic disease. MRI of the cervical spine revealed a normal cervical spinal cord and mild cervical spondylosis. Therapy with pyridostigmine was initiated, and the patient was referred to this hospital for further evaluation.
On presentation to this hospital, the patient reported that pyridostigmine had had no effect on his weakness or chronic diplopia but that his difficulty chewing had improved. However, 5 weeks after the initiation of treatment, the difficulty chewing had worsened despite continued therapy with pyridostigmine. The patient reported new weakness in the legs, with difficulty rising from a seated position. He also reported increasing frequency of the fasciculations and one fall at home. He had a history of hypertension, treated Lyme disease, psoriasis, and a traumatic compression fracture of the thoracic spine. Surgeries included cataract extractions and correction of a retinal detachment. He had no known allergies. Medications included pyridostigmine, hydrochlorothiazide, irbesartan, zolpidem, a multivitamin, and topical calcipotriene. He drank two alcoholic beverages weekly and did not smoke tobacco or use illicit drugs. There was no family history of neurologic disease.
On examination at this hospital, the temperature was 36.4[degrees]C, the blood pressure 146/82 mm Hg, the pulse 66 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 22.7. The patient's mental status was normal. Cranial-nerve testing revealed exophoria with upgaze that was present in both eyes but was most prominent on the right side. There was slightly reduced and slowed elevation of the eyebrows and mild weakness on eye closure and cheek inflation. Tongue movements were quick but weak with attempted opposition in the cheek. Lingual dysarthria was observed.
There was reduced bulk of the temporalis, periscapular, pectoralis, quadriceps, and intrinsic hand muscles. Diffuse fasciculations were observed in the face, tongue, trunk, quadriceps, and arms. Some fasciculations were forceful enough to result in movement of the fingers. Mild weakness was noted in the intrinsic hand muscles and proximal muscles of the arms and legs. Deep-tendon reflexes were asymmetrically brisk in the arms and normal in the legs. The plantar responses were flexor. Sensation, coordination, and gait were normal. Gynecomastia was present. The remainder of the examination was normal. The creatine kinase level was 498 U per liter (reference range, 60 to 400), and results of serum protein electrophoresis were normal. Serum testing for human immunodeficiency virus types 1 and 2 antibodies and p24 antigen was negative.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Amyotrophic Lateral Sclerosis (ALS)\n\nThe patient's symptoms of progressive weakness, difficulty chewing, and muscle cramps, along with the physical findings of muscle atrophy, fasciculations, and brisk deep-tendon reflexes, are suggestive of a motor neuron disease. The absence of sensory symptoms and the normal results of sensory examination rule out diseases that affect sensory neurons. The negative tests for acetylcholine receptor antibodies and muscle-specific tyrosine kinase antibodies, along with the lack of improvement with pyridostigmine, make myasthenia gravis unlikely. The presence of both upper and lower motor neuron signs in multiple body regions, along with the progressive course of the disease, are consistent with a diagnosis of ALS.""
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        ""content"": ""The patient's symptoms of weakness in the muscles of the shoulders and arms, difficulty chewing, excess salivation, slurred speech, and weight loss, along with the physical examination findings of atrophy and fasciculations of the deltoid muscles, reduced bulk of the temporalis, periscapular, pectoralis, quadriceps, and intrinsic hand muscles, and diffuse fasciculations in the face, tongue, trunk, quadriceps, and arms, are all indicative of a motor neuron disease. The absence of sensory symptoms and the normal results of sensory examination further support this. The presence of both upper and lower motor neuron signs (atrophy, fasciculations, and weakness along with brisk deep tendon reflexes) is characteristic of amyotrophic lateral sclerosis (ALS). The lack of response to pyridostigmine, a medication used to treat myasthenia gravis, also supports the diagnosis of ALS, as myasthenia gravis is a disorder of the neuromuscular junction and would typically respond to this medication.\n\nDiagnosis: Amyotrophic lateral sclerosis (ALS)""
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        ""content"": ""The patient is a 60-year-old man presenting with progressive weakness, difficulty chewing, and fasciculations. The differential diagnosis includes myasthenia gravis, Lambert-Eaton syndrome, and amyotrophic lateral sclerosis (ALS). Myasthenia gravis and Lambert-Eaton syndrome are both autoimmune conditions that affect the neuromuscular junction, leading to muscle weakness. However, the patient's negative tests for acetylcholine receptor antibodies and muscle-specific tyrosine kinase antibodies make these diagnoses less likely. Additionally, the patient did not respond to pyridostigmine, a medication used to treat myasthenia gravis. ALS, also known as Lou Gehrig's disease, is a neurodegenerative disorder that affects motor neurons in the brain and spinal cord. The patient's symptoms of progressive muscle weakness, fasciculations, and dysarthria, along with the presence of brisk deep tendon reflexes in the arms, are consistent with ALS. The patient's normal sensory examination and lack of bladder or bowel symptoms also support this diagnosis, as ALS typically spares sensory and autonomic neurons.\n\nDiagnosis: Amyotrophic lateral sclerosis (ALS)""
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10.1056/NEJMcpc1900143,Case 10-2019: A 69-Year-Old Man with Progressive Dyspnea,,Idiopathic pulmonary fibrosis,Unclassifiable progressive fibrotic interstitial lung disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 69-year-old man was evaluated in the pulmonary clinic of this hospital because of progressive dyspnea.
Ten years before this evaluation, the patient noticed labored breathing with activity, initially while he was climbing stairs and then while he was walking on level ground. He was evaluated at another hospital with a treadmill stress test and transthoracic echocardiography; the results of both studies were reportedly normal. The dyspnea abated, and the patient was in his usual state of health until 30 months before this evaluation, when fatigue, malaise, sore throat, rhinorrhea, and arthralgias, including arm and chest pain, developed. He sought attention in the emergency department of the other hospital. The hemoglobin level was 13.6 mg per deciliter (reference range, 14.0 to 18.0). Levels of electrolytes and creatinine, results of liver-function tests, and the white-cell and platelet counts were normal. A chest radiograph (Figure 1) showed moderately inflated lungs, with subcentimeter, faint nodular opacities in the upper lung zones. Azithromycin was prescribed.	
Figure 1 
Dr. Jennifer F. Feneis: Computed tomography (CT) of the chest, performed without the administration of intravenous contrast material (Figure 1), revealed diffuse subpleural reticulation, without honeycombing or traction bronchiectasis or bronchiolectasis. The patient had a few bilateral, scattered, solid pulmonary nodules, measuring 3 to 6 mm in diameter. There was mild enlargement of a low right paratracheal lymph node (11 mm in short axis) and of a right hilar lymph node (14 mm), and aortic and coronary atherosclerosis was present.
Dr. Montesi: Seventeen months before this evaluation, the patient was seen by his primary care physician at the other hospital for a several-week history of rhinorrhea and a cough that was intermittently productive of green sputum. A radiograph of the sinuses showed opacification of the right frontal sinus but no evidence of sinusitis. Twelve months before this evaluation, the patient reported the insidious onset of exertional dyspnea, which he had first noticed while he was climbing several flights of stairs. The dyspnea had progressed and occurred with less exertion. He had traveled to Denver and felt increased dyspnea at the high altitude.
Six months before this evaluation, a nuclear stress test with myocardial perfusion imaging, performed because of several weeks of persistent exertional dyspnea, revealed a small area of distal anterior ischemia. Three months later, transthoracic echocardiography, performed because of ongoing dyspnea, revealed a left ventricular ejection fraction of 70%, mild concentric left ventricular hypertrophy, mild aortic dilatation, and no evidence of valvular disease; the right ventricular systolic pressure could not be estimated.
Four weeks before this evaluation, the patient was seen by his primary care physician for ongoing dyspnea, which occurred with any amount of exertion, and cough. Additional imaging studies were performed.
Dr. Feneis: Pulmonary CT angiography (Figure 1) revealed persistence of the diffuse subpleural reticular opacities that had been seen on the initial CT scan, which involved all the lobes without distinct apical or basal predominance. The patient had new bilateral traction bronchiolectasis, new dilatation of the main pulmonary artery (33 mm in diameter), and increased enlargement of mediastinal lymph nodes (including a low right paratracheal lymph node measuring 17 mm in short axis) and of a right hilar lymph node (17 mm). There were new ill-defined ground-glass opacities in both lungs, but these were most likely due to low lung volumes and the fact that the images were obtained during the expiratory phase. There were also a few lobular areas of hypoattenuating parenchyma in both lungs, a finding suggestive of mild air trapping. There was no evidence of pulmonary embolism.
These imaging features are consistent with fibrotic interstitial lung disease. On the basis of these features, the differential diagnosis includes hypersensitivity pneumonitis, usual interstitial pneumonia, and nonspecific interstitial pneumonia. The presence of bilateral, albeit mild, air trapping increases the likelihood of hypersensitivity pneumonitis 1; however, this amount of air trapping is not extensive enough to rule out a possible diagnosis of usual interstitial pneumonia.2
Dr. Montesi: Two weeks before this evaluation, the patient was evaluated by a pulmonologist at the other hospital. Pulmonary-function testing revealed a forced expiratory volume in 1 second (FEV1) of 2.50 liters (82% of the predicted value), a forced vital capacity (FVC) of 2.90 liters (73% of the predicted value), and a ratio of FEV1 to FVC of 0.86; there was no change with the administration of a bronchodilator. The total lung capacity was 3.92 liters (61% of the predicted value), and the carbon monoxide diffusion capacity (corrected for hemoglobin level) was 45% of the predicted value. These results were interpreted as indicative of a restrictive ventilatory deficit with diffusion impairment. The patient was referred to the pulmonary clinic of this hospital.
On evaluation, the patient reported ongoing dyspnea that was provoked by any amount of exertion and an occasional morning cough that was productive of scant greenish-brown mucus. He reported no fever, weight loss, hemoptysis, chest pain, wheezing, weakness, fatigue, dry eyes, dry mouth, heartburn, dysphagia, rash, Raynaud's phenomenon, edema, myalgias, or arthralgias. His medical history included hypertension, hyperlipidemia, coronary-artery calcifications, right bundle-branch block, osteoarthritis of the knees and shoulders, prostatic hypertrophy, and gastroesophageal reflux disease. In addition, he had undergone right carotid endarterectomy owing to carotid-artery stenosis, right total knee replacement owing to osteoarthritis, removal of a tubular adenoma of the colon, and Mohs surgery for removal of multiple basal-cell carcinomas. Medications included aspirin, rosuvastatin, and omeprazole. There had been no adverse reactions to medications, but exposure to cats and wool caused watery eyes.
The patient had smoked one pack of cigarettes daily for 10 years and had quit more than 40 years earlier; he had smoked five cigars per week for 15 years and had quit 5 years earlier. He drank one serving of liquor daily with dinner. He lived in coastal Massachusetts and had previously resided in the Midwest and in the southeastern United States. He worked in marketing and consulting and traveled extensively, but he had no known occupational or inhalational exposures. He had no pets or exposure to molds. His father had died of a myocardial infarction at 54 years of age, and his mother had had basal-cell carcinoma; there was no family history of lung or autoimmune disease, and his four children were healthy.
The temperature was 36.8[degrees]C, the heart rate 68 beats per minute, the blood pressure 134/78 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air at rest and 95% after he had climbed one flight of stairs. Auscultation of the lungs revealed bilateral crackles at end inspiration that were most prominent over the right lung base. The remainder of the examination was normal.
Hypersensitivity pneumonitis screening tests were negative, as were tests for antinuclear antibodies, antineutrophil cytoplasmic antibodies (ANCAs), rheumatoid factor, anti-cyclic citrullinated peptide, anti-Smith antibodies, antiribonucleoprotein, and antibodies to Ro (SSA), La (SSB), Scl-70, and Jo-1. The aldolase level was 5.0 U per liter (reference range, <7.7), the creatine kinase level 127 U per liter (reference range, 60 to 400), the erythrocyte-sedimentation rate 22 mm per hour (reference range, 0 to 13), and the D-dimer level 1239 ng per milliliter (reference range,  ).
A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 69-year-old man was evaluated in the pulmonary clinic of this hospital because of progressive dyspnea.
Ten years before this evaluation, the patient noticed labored breathing with activity, initially while he was climbing stairs and then while he was walking on level ground. He was evaluated at another hospital with a treadmill stress test and transthoracic echocardiography; the results of both studies were reportedly normal. The dyspnea abated, and the patient was in his usual state of health until 30 months before this evaluation, when fatigue, malaise, sore throat, rhinorrhea, and arthralgias, including arm and chest pain, developed. He sought attention in the emergency department of the other hospital. The hemoglobin level was 13.6 mg per deciliter (reference range, 14.0 to 18.0). Levels of electrolytes and creatinine, results of liver-function tests, and the white-cell and platelet counts were normal. A chest radiograph (Figure 1) showed moderately inflated lungs, with subcentimeter, faint nodular opacities in the upper lung zones. Azithromycin was prescribed.	
Figure 1 
Dr. Jennifer F. Feneis: Computed tomography (CT) of the chest, performed without the administration of intravenous contrast material (Figure 1), revealed diffuse subpleural reticulation, without honeycombing or traction bronchiectasis or bronchiolectasis. The patient had a few bilateral, scattered, solid pulmonary nodules, measuring 3 to 6 mm in diameter. There was mild enlargement of a low right paratracheal lymph node (11 mm in short axis) and of a right hilar lymph node (14 mm), and aortic and coronary atherosclerosis was present.
Dr. Montesi: Seventeen months before this evaluation, the patient was seen by his primary care physician at the other hospital for a several-week history of rhinorrhea and a cough that was intermittently productive of green sputum. A radiograph of the sinuses showed opacification of the right frontal sinus but no evidence of sinusitis. Twelve months before this evaluation, the patient reported the insidious onset of exertional dyspnea, which he had first noticed while he was climbing several flights of stairs. The dyspnea had progressed and occurred with less exertion. He had traveled to Denver and felt increased dyspnea at the high altitude.
Six months before this evaluation, a nuclear stress test with myocardial perfusion imaging, performed because of several weeks of persistent exertional dyspnea, revealed a small area of distal anterior ischemia. Three months later, transthoracic echocardiography, performed because of ongoing dyspnea, revealed a left ventricular ejection fraction of 70%, mild concentric left ventricular hypertrophy, mild aortic dilatation, and no evidence of valvular disease; the right ventricular systolic pressure could not be estimated.
Four weeks before this evaluation, the patient was seen by his primary care physician for ongoing dyspnea, which occurred with any amount of exertion, and cough. Additional imaging studies were performed.
Dr. Feneis: Pulmonary CT angiography (Figure 1) revealed persistence of the diffuse subpleural reticular opacities that had been seen on the initial CT scan, which involved all the lobes without distinct apical or basal predominance. The patient had new bilateral traction bronchiolectasis, new dilatation of the main pulmonary artery (33 mm in diameter), and increased enlargement of mediastinal lymph nodes (including a low right paratracheal lymph node measuring 17 mm in short axis) and of a right hilar lymph node (17 mm). There were new ill-defined ground-glass opacities in both lungs, but these were most likely due to low lung volumes and the fact that the images were obtained during the expiratory phase. There were also a few lobular areas of hypoattenuating parenchyma in both lungs, a finding suggestive of mild air trapping. There was no evidence of pulmonary embolism.
These imaging features are consistent with fibrotic interstitial lung disease. On the basis of these features, the differential diagnosis includes hypersensitivity pneumonitis, usual interstitial pneumonia, and nonspecific interstitial pneumonia. The presence of bilateral, albeit mild, air trapping increases the likelihood of hypersensitivity pneumonitis 1; however, this amount of air trapping is not extensive enough to rule out a possible diagnosis of usual interstitial pneumonia.2
Dr. Montesi: Two weeks before this evaluation, the patient was evaluated by a pulmonologist at the other hospital. Pulmonary-function testing revealed a forced expiratory volume in 1 second (FEV1) of 2.50 liters (82% of the predicted value), a forced vital capacity (FVC) of 2.90 liters (73% of the predicted value), and a ratio of FEV1 to FVC of 0.86; there was no change with the administration of a bronchodilator. The total lung capacity was 3.92 liters (61% of the predicted value), and the carbon monoxide diffusion capacity (corrected for hemoglobin level) was 45% of the predicted value. These results were interpreted as indicative of a restrictive ventilatory deficit with diffusion impairment. The patient was referred to the pulmonary clinic of this hospital.
On evaluation, the patient reported ongoing dyspnea that was provoked by any amount of exertion and an occasional morning cough that was productive of scant greenish-brown mucus. He reported no fever, weight loss, hemoptysis, chest pain, wheezing, weakness, fatigue, dry eyes, dry mouth, heartburn, dysphagia, rash, Raynaud's phenomenon, edema, myalgias, or arthralgias. His medical history included hypertension, hyperlipidemia, coronary-artery calcifications, right bundle-branch block, osteoarthritis of the knees and shoulders, prostatic hypertrophy, and gastroesophageal reflux disease. In addition, he had undergone right carotid endarterectomy owing to carotid-artery stenosis, right total knee replacement owing to osteoarthritis, removal of a tubular adenoma of the colon, and Mohs surgery for removal of multiple basal-cell carcinomas. Medications included aspirin, rosuvastatin, and omeprazole. There had been no adverse reactions to medications, but exposure to cats and wool caused watery eyes.
The patient had smoked one pack of cigarettes daily for 10 years and had quit more than 40 years earlier; he had smoked five cigars per week for 15 years and had quit 5 years earlier. He drank one serving of liquor daily with dinner. He lived in coastal Massachusetts and had previously resided in the Midwest and in the southeastern United States. He worked in marketing and consulting and traveled extensively, but he had no known occupational or inhalational exposures. He had no pets or exposure to molds. His father had died of a myocardial infarction at 54 years of age, and his mother had had basal-cell carcinoma; there was no family history of lung or autoimmune disease, and his four children were healthy.
The temperature was 36.8[degrees]C, the heart rate 68 beats per minute, the blood pressure 134/78 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air at rest and 95% after he had climbed one flight of stairs. Auscultation of the lungs revealed bilateral crackles at end inspiration that were most prominent over the right lung base. The remainder of the examination was normal.
Hypersensitivity pneumonitis screening tests were negative, as were tests for antinuclear antibodies, antineutrophil cytoplasmic antibodies (ANCAs), rheumatoid factor, anti-cyclic citrullinated peptide, anti-Smith antibodies, antiribonucleoprotein, and antibodies to Ro (SSA), La (SSB), Scl-70, and Jo-1. The aldolase level was 5.0 U per liter (reference range, <7.7), the creatine kinase level 127 U per liter (reference range, 60 to 400), the erythrocyte-sedimentation rate 22 mm per hour (reference range, 0 to 13), and the D-dimer level 1239 ng per milliliter (reference range,  ).
A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of progressive dyspnea, fatigue, malaise, sore throat, rhinorrhea, and arthralgias. Imaging studies revealed diffuse subpleural reticulation, without honeycombing or traction bronchiectasis or bronchiolectasis, and a few bilateral, scattered, solid pulmonary nodules. Pulmonary-function testing revealed a restrictive ventilatory deficit with diffusion impairment. The patient's symptoms, imaging findings, and pulmonary function test results are consistent with interstitial lung disease. The presence of bilateral, albeit mild, air trapping increases the likelihood of hypersensitivity pneumonitis; however, this amount of air trapping is not extensive enough to rule out a possible diagnosis of usual interstitial pneumonia. Given the patient's history, clinical presentation, and test results, the most likely diagnosis is interstitial lung disease. \n\nDiagnosis: Interstitial Lung Disease""
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        ""content"": ""The patient has a history of progressive dyspnea, fatigue, malaise, and arthralgias. Imaging studies revealed diffuse subpleural reticulation, without honeycombing or traction bronchiectasis or bronchiolectasis, and a few bilateral, scattered, solid pulmonary nodules. Pulmonary-function testing revealed a restrictive ventilatory deficit with diffusion impairment. The patient's symptoms, imaging findings, and pulmonary function test results are consistent with interstitial lung disease. The presence of bilateral, albeit mild, air trapping increases the likelihood of hypersensitivity pneumonitis; however, this amount of air trapping is not extensive enough to rule out a possible diagnosis of usual interstitial pneumonia. Given the patient's history, clinical presentation, and test results, the most likely diagnosis is interstitial lung disease.\n\nDiagnosis: Interstitial Lung Disease""
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        ""content"": ""The patient is a 69-year-old man with a history of smoking and a 10-year history of progressive dyspnea. His symptoms have worsened over the past 30 months, with the addition of fatigue, malaise, sore throat, rhinorrhea, and arthralgias. His chest radiograph shows subcentimeter, faint nodular opacities in the upper lung zones. His CT scan reveals diffuse subpleural reticulation, without honeycombing or traction bronchiectasis or bronchiolectasis. He has a few bilateral, scattered, solid pulmonary nodules, measuring 3 to 6 mm in diameter. There is mild enlargement of a low right paratracheal lymph node and of a right hilar lymph node, and aortic and coronary atherosclerosis is present. His pulmonary function tests reveal a restrictive ventilatory deficit with diffusion impairment. His symptoms, imaging findings, and pulmonary function tests are consistent with a diagnosis of interstitial lung disease. The differential diagnosis includes hypersensitivity pneumonitis, usual interstitial pneumonia, and nonspecific interstitial pneumonia. Given the patient's history of smoking, the presence of nodules on imaging, and the absence of a history of exposure to known causes of hypersensitivity pneumonitis, usual interstitial pneumonia (also known as idiopathic pulmonary fibrosis) is the most likely diagnosis.\n\nDiagnosis: Usual interstitial pneumonia (idiopathic pulmonary fibrosis)""
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10.1056/NEJMcpc1900140,"Case 9-2019: A 62-Year-Old Man with Atrial Fibrillation, Depression, and Worsening Anxiety",,Symptomatic atrial fibrillation with associated anxiety,Recurrent atrial fibrillation in the context of generalized anxiety disorder and major depressive disorder.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 62-year-old man was evaluated in the psychiatry clinic of this hospital because of depression and worsening anxiety.
The patient had received a diagnosis of major depressive disorder from a psychiatrist 15 years before this presentation, after his wife had received a diagnosis of cancer while she was pregnant with their daughter. The patient had severe depression and the onset of generalized anxiety symptoms in association with his wife's progressive illness and ultimate death. Trials of buspirone, sertraline, and escitalopram were ineffective, but depression and anxiety symptoms diminished with the use of citalopram and clonazepam. The patient continued to use these two medications to control his depression and anxiety, and he stopped seeing his psychiatrist after almost 7 years of treatment, remaining under the care of his primary care physician. Six years later, he discontinued citalopram.
One year later (20 months before this presentation), the patient contacted his primary care physician to report recurrent anxiety, depression, and lethargy. Citalopram was restarted. On evaluation in the primary care clinic 3 weeks later, he reported that his condition had improved with the use of medication but lethargy persisted. On examination, the blood pressure was 108/75 mm Hg, and the heart rate 130 beats per minute and irregular. An electrocardiogram (ECG) and rhythm strip (Fig. 1) showed new atrial fibrillation with a rapid ventricular response. Treatment with metoprolol succinate and dabigatran was initiated, and during the next 4 weeks, the metoprolol dose was adjusted to control the heart rate. Transthoracic echocardiography revealed left atrial and left ventricular dilatation, a low-normal left ventricular ejection fraction, mild left ventricular hypertrophy, and no clinically significant valvular disease.	
Figure 1 
Four weeks later (18 months before this presentation), the patient was evaluated in the cardiology clinic of this hospital; he reported daily episodes of palpitations. The blood pressure was 140/60 mm Hg, and the heart rate 60 beats per minute and regular. An ECG showed normal sinus rhythm with a slightly prolonged corrected QT (QTc) interval, measuring 466 msec. Holter monitoring for 24 hours was performed to assess for control of the heart rate; the average heart rate was 65 beats per minute, the maximum heart rate was 84 beats per minute, and no episodes of atrial fibrillation were detected.
Approximately 1 year later (5 months before this presentation), the patient reported several weeks of heightened anxiety and recurrent depressive symptoms, which were in part due to financial stressors and the fact that his girlfriend of several years had received a diagnosis of recurrent cancer. The patient was binge drinking intermittently. He reported weekly panic attacks that were characterized by a ""racing"" heart, light-headedness, restlessness, and shaking; the panic attacks lasted 30 minutes and had some correlation with episodes of increased alcohol intake. After 4 months of persistent symptoms, the patient sought psychiatry consultation.
One month later, on evaluation in the psychiatry clinic, the patient described his mood as depressed and anxious. He had persistent anxiety and panic symptoms, as well as worsened depressive symptoms, including difficulty concentrating, low energy, low self-worth, and sleeping for 2 to 3 hours more than usual each night. He reported having a stable appetite but had lost 6.4 kg during the preceding 18 months. He had had no hallucinations or thoughts of harming himself or others. He again reported weekly panic attacks that were characterized by a racing heart, light-headedness, restlessness, shaking, and generalized weakness. Some of these episodes had lasted several hours. There were no predictable triggers; the episodes had occurred at all times of day and had occasionally awakened him from sleep. He reported no chest pain or dyspnea.
The patient's medical history was notable for atrial fibrillation, hypertension, hyperlipidemia, asthma, gastroesophageal reflux, osteoarthritis, colonic polyps, and vitamin D deficiency. He had undergone appendectomy and knee arthroplasty. He had had no psychiatric hospitalizations. Medications were citalopram, clonazepam, dabigatran, metoprolol succinate, fluticasone, and albuterol. Montelukast had caused an adverse reaction, and sertraline had caused paresthesia.
The patient's parents had a history of heavy alcohol use. Several paternal relatives had a history of depression, and a maternal aunt had died of an intentional drug overdose. His mother had had emphysema and had died of breast cancer. His father had had hyperlipidemia and had died of asbestosis. The patient was born and raised in New England. He had completed an undergraduate degree and had worked at a university for 20 years; in the past year, because of financial stressors, he had begun to work two jobs in retail. The patient did not smoke cigarettes and reported no illicit drug use. He reported drinking 4 to 6 servings of whiskey weekly, with occasional binges.
On examination, the blood pressure was 112/67 mm Hg, and the heart rate 64 beats per minute and regular. The patient was well groomed, alert, oriented, and cooperative. He had fluent speech. His mood was sad and dysphoric, and his affect was flat. His thought process was goal-directed, and his attention was intact. He had good insight into his worsening depressive and anxiety symptoms. On review of laboratory data obtained during the previous 5 months, results of tests of thyroid function, kidney function, and liver function were normal, as were electrolyte levels and the complete blood count. Treatment with clonazepam and citalopram was continued, and aripiprazole was initiated.
Three weeks after this presentation, the patient had fatigue and several episodes of palpitations followed by near syncope. He had no chest pain or dyspnea. He presented to the emergency department of this hospital. The temperature was 36.6[degrees]C, the blood pressure 163/92 mm Hg, and the heart rate 120 beats per minute and irregular. He appeared to be well. Results of urinalysis, urine toxicologic testing, and kidney-function tests were normal, as were electrolyte and troponin T levels and the complete blood count. An ECG showed atrial fibrillation with a rapid ventricular response and nonspecific ST-segment changes. Intravenous and oral diltiazem were administered. While the patient was undergoing telemetry monitoring, he had two episodes of near syncope that correlated with sinus pauses of 6 seconds and 7 seconds. He was admitted to the cardiology unit, and a dual-chamber permanent pacemaker was placed. Metoprolol succinate was continued, and the patient was discharged home 2 days later.
Two weeks later, the patient was seen in the psychiatry clinic. He reported marked improvement in his mood and energy after the initiation of aripiprazole; he did not report any further episodes of anxiety or panic. He had stable hypersomnia, ongoing fatigue, and late-day mental ""fogginess."" On evaluation at the primary care clinic 3 days later, the blood pressure was 124/82 mm Hg, and the heart rate 69 beats per minute and regular. Metoprolol was discontinued because of fatigue.
Three weeks later, the patient reported to his psychiatrist that he had missed work because of increasing anxiousness, with the feeling of a racing and ""thumping"" heart and excessive worry. He reported that aripiprazole was not controlling his anxiety symptoms. He stated that his mood was ""good"" and his energy, sleep, and appetite were unchanged, but he had noticed weakness in his legs, restlessness, and some new difficulty breathing in association with his anxiety symptoms. The aripiprazole dose was increased.
Several days later, a diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 62-year-old man was evaluated in the psychiatry clinic of this hospital because of depression and worsening anxiety.
The patient had received a diagnosis of major depressive disorder from a psychiatrist 15 years before this presentation, after his wife had received a diagnosis of cancer while she was pregnant with their daughter. The patient had severe depression and the onset of generalized anxiety symptoms in association with his wife's progressive illness and ultimate death. Trials of buspirone, sertraline, and escitalopram were ineffective, but depression and anxiety symptoms diminished with the use of citalopram and clonazepam. The patient continued to use these two medications to control his depression and anxiety, and he stopped seeing his psychiatrist after almost 7 years of treatment, remaining under the care of his primary care physician. Six years later, he discontinued citalopram.
One year later (20 months before this presentation), the patient contacted his primary care physician to report recurrent anxiety, depression, and lethargy. Citalopram was restarted. On evaluation in the primary care clinic 3 weeks later, he reported that his condition had improved with the use of medication but lethargy persisted. On examination, the blood pressure was 108/75 mm Hg, and the heart rate 130 beats per minute and irregular. An electrocardiogram (ECG) and rhythm strip (Fig. 1) showed new atrial fibrillation with a rapid ventricular response. Treatment with metoprolol succinate and dabigatran was initiated, and during the next 4 weeks, the metoprolol dose was adjusted to control the heart rate. Transthoracic echocardiography revealed left atrial and left ventricular dilatation, a low-normal left ventricular ejection fraction, mild left ventricular hypertrophy, and no clinically significant valvular disease.	
Figure 1 
Four weeks later (18 months before this presentation), the patient was evaluated in the cardiology clinic of this hospital; he reported daily episodes of palpitations. The blood pressure was 140/60 mm Hg, and the heart rate 60 beats per minute and regular. An ECG showed normal sinus rhythm with a slightly prolonged corrected QT (QTc) interval, measuring 466 msec. Holter monitoring for 24 hours was performed to assess for control of the heart rate; the average heart rate was 65 beats per minute, the maximum heart rate was 84 beats per minute, and no episodes of atrial fibrillation were detected.
Approximately 1 year later (5 months before this presentation), the patient reported several weeks of heightened anxiety and recurrent depressive symptoms, which were in part due to financial stressors and the fact that his girlfriend of several years had received a diagnosis of recurrent cancer. The patient was binge drinking intermittently. He reported weekly panic attacks that were characterized by a ""racing"" heart, light-headedness, restlessness, and shaking; the panic attacks lasted 30 minutes and had some correlation with episodes of increased alcohol intake. After 4 months of persistent symptoms, the patient sought psychiatry consultation.
One month later, on evaluation in the psychiatry clinic, the patient described his mood as depressed and anxious. He had persistent anxiety and panic symptoms, as well as worsened depressive symptoms, including difficulty concentrating, low energy, low self-worth, and sleeping for 2 to 3 hours more than usual each night. He reported having a stable appetite but had lost 6.4 kg during the preceding 18 months. He had had no hallucinations or thoughts of harming himself or others. He again reported weekly panic attacks that were characterized by a racing heart, light-headedness, restlessness, shaking, and generalized weakness. Some of these episodes had lasted several hours. There were no predictable triggers; the episodes had occurred at all times of day and had occasionally awakened him from sleep. He reported no chest pain or dyspnea.
The patient's medical history was notable for atrial fibrillation, hypertension, hyperlipidemia, asthma, gastroesophageal reflux, osteoarthritis, colonic polyps, and vitamin D deficiency. He had undergone appendectomy and knee arthroplasty. He had had no psychiatric hospitalizations. Medications were citalopram, clonazepam, dabigatran, metoprolol succinate, fluticasone, and albuterol. Montelukast had caused an adverse reaction, and sertraline had caused paresthesia.
The patient's parents had a history of heavy alcohol use. Several paternal relatives had a history of depression, and a maternal aunt had died of an intentional drug overdose. His mother had had emphysema and had died of breast cancer. His father had had hyperlipidemia and had died of asbestosis. The patient was born and raised in New England. He had completed an undergraduate degree and had worked at a university for 20 years; in the past year, because of financial stressors, he had begun to work two jobs in retail. The patient did not smoke cigarettes and reported no illicit drug use. He reported drinking 4 to 6 servings of whiskey weekly, with occasional binges.
On examination, the blood pressure was 112/67 mm Hg, and the heart rate 64 beats per minute and regular. The patient was well groomed, alert, oriented, and cooperative. He had fluent speech. His mood was sad and dysphoric, and his affect was flat. His thought process was goal-directed, and his attention was intact. He had good insight into his worsening depressive and anxiety symptoms. On review of laboratory data obtained during the previous 5 months, results of tests of thyroid function, kidney function, and liver function were normal, as were electrolyte levels and the complete blood count. Treatment with clonazepam and citalopram was continued, and aripiprazole was initiated.
Three weeks after this presentation, the patient had fatigue and several episodes of palpitations followed by near syncope. He had no chest pain or dyspnea. He presented to the emergency department of this hospital. The temperature was 36.6[degrees]C, the blood pressure 163/92 mm Hg, and the heart rate 120 beats per minute and irregular. He appeared to be well. Results of urinalysis, urine toxicologic testing, and kidney-function tests were normal, as were electrolyte and troponin T levels and the complete blood count. An ECG showed atrial fibrillation with a rapid ventricular response and nonspecific ST-segment changes. Intravenous and oral diltiazem were administered. While the patient was undergoing telemetry monitoring, he had two episodes of near syncope that correlated with sinus pauses of 6 seconds and 7 seconds. He was admitted to the cardiology unit, and a dual-chamber permanent pacemaker was placed. Metoprolol succinate was continued, and the patient was discharged home 2 days later.
Two weeks later, the patient was seen in the psychiatry clinic. He reported marked improvement in his mood and energy after the initiation of aripiprazole; he did not report any further episodes of anxiety or panic. He had stable hypersomnia, ongoing fatigue, and late-day mental ""fogginess."" On evaluation at the primary care clinic 3 days later, the blood pressure was 124/82 mm Hg, and the heart rate 69 beats per minute and regular. Metoprolol was discontinued because of fatigue.
Three weeks later, the patient reported to his psychiatrist that he had missed work because of increasing anxiousness, with the feeling of a racing and ""thumping"" heart and excessive worry. He reported that aripiprazole was not controlling his anxiety symptoms. He stated that his mood was ""good"" and his energy, sleep, and appetite were unchanged, but he had noticed weakness in his legs, restlessness, and some new difficulty breathing in association with his anxiety symptoms. The aripiprazole dose was increased.
Several days later, a diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 62-year-old man with a history of major depressive disorder and anxiety, presenting with recurrent symptoms of depression and anxiety, as well as new symptoms of palpitations, near syncope, and fatigue. His medical history is notable for atrial fibrillation, hypertension, hyperlipidemia, asthma, gastroesophageal reflux, osteoarthritis, colonic polyps, and vitamin D deficiency. The differential diagnosis for this patient includes recurrent major depressive disorder, generalized anxiety disorder, panic disorder, cardiac arrhythmias, and side effects of medications. The patient's symptoms of palpitations and near syncope, as well as his history of atrial fibrillation, suggest a cardiac etiology. However, his psychiatric symptoms, including depression and anxiety, could also be contributing to his presentation. His medications, including citalopram and clonazepam, could potentially cause side effects such as fatigue and palpitations. However, the patient's symptoms improved with the initiation of aripiprazole, suggesting that his psychiatric symptoms were a major contributor to his presentation. His symptoms of a racing and \""thumping\"" heart, excessive worry, and difficulty breathing are characteristic of panic disorder. Therefore, the most likely diagnosis for this patient is panic disorder.\n\nDiagnosis: Panic Disorder.""
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10.1056/NEJMcpc1810395,"Case 8-2019: A 58-Year-Old Woman with Vision Loss, Headaches, and Oral Ulcers","Hematocrit (%)   43.2 44.7
Hemoglobin (g/dl)   14.0 15.7
White-cell count (per mm3)   10,410 15,490
Differential count (%)
Neutrophils   89.7 88.0
Lymphocytes   7.9 3.8
Monocytes   1.4 6.8
Eosinophils   0 0
Basophils   0.1 0.1
Platelet count (per mm3
)   276,000 248,000
Erythrocyte-sedimentation rate (mm/hr)  0 2 2
C-reactive protein (mg/liter)  .0 1.1 0.9 2.5
C3 (mg/dl)  127
C4 (mg/dl) 12–39 33
Urine
Color Yellow Yellow Yellow
Clarity Clear Clear Clear
Glucose Negative 2+ Negative
Bilirubin Negative Negative Negative
Ketones Negative Negative 1+
Specific gravity   1.016 1.024
Blood Negative Negative 1+
pH   7.0 5.0
Protein Negative Negative Negative
Urobilinogen Negative Negative Negative
Nitrite Negative Negative Negative
Leukocyte esterase Negative Negative Negative
Red cells (per high-power field)     5–10
White cells (per high-power field)      
Mucin None None Present",Ocular syphilis.,"Syphilis involving the eyes and central nervous system, possibly in the context of advanced human immunodeficiency virus type 1 infection.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 58-year-old woman was admitted to this hospital for vision loss in the right eye, acute progressive vision loss in the left eye, headaches, and rashes.
Four years before admission, a brown, nonpainful, nonpruritic, maculopapular rash developed on the trunk. Approximately 4 weeks later, the rash had spontaneously resolved; however, painful, peeling, erythematous papules had appeared on the hands and in the web spaces between the fingers, and oral and nasal aphthous ulcerations had occurred. During the following weeks, the hand lesions and nasal ulcers spontaneously resolved. The oral ulcers waxed and waned but continued to be present intermittently.
Dr. Lana M. Rifkin: Three and a half years before admission, bilateral temporal pingueculae were identified on routine ophthalmologic examination. Approximately 18 months later, pain and redness developed in both eyes; the patient received a diagnosis of bilateral conjunctival ulcerations, and prednisolone eyedrops were prescribed. Four weeks later, she returned to the ophthalmology clinic and reported headaches on the right side and 3 days of bilateral blurry vision, photophobia that led her to wear sunglasses indoors, and redness and pain in the right eye. She rated the eye pain as 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Bromfenac eyedrops were prescribed, and she was referred to an ophthalmologist who specialized in uveitis. Examination by the uveitis specialist revealed scleritis in the right eye and oral ulcers; prednisolone eyedrops were resumed, and oral piroxicam was prescribed.
Dr. Yokose: During the next 4 weeks, the blurry vision and photophobia decreased. Five weeks later (21 months before admission), the patient was evaluated in the rheumatology clinic of this hospital for worsened oral ulcers and recurrent blurry vision in the left eye that had developed as the glucocorticoid dose was tapered. Examination was notable for aphthous ulcers on the tongue and several nasal erosions. Blood levels of electrolytes, urea nitrogen, creatinine, calcium, total protein, albumin, and globulin and results of liver-function tests were normal. Tests for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, and anti-cyclic citrullinated peptide were negative; other laboratory test results are shown in Table 1.	
Table 1
Dr. Rifkin: One month later, the patient returned to the ophthalmology clinic for follow-up. She reported pain in the left eye (rated as 7 out of 10) and recurrent blurry vision and photophobia. Examination revealed new scleritis in the left eye.
Dr. Yokose: During the next 6 months, the patient could not be fully weaned off glucocorticoid therapy because of both chronic asthma and worsening oral ulcerations that occurred with medication tapers. Azathioprine, adalimumab, and intravitreal glucocorticoids were administered for scleritis and oral ulcers. Because testing for HLA-B51 was positive, a working diagnosis of atypical Behcet's disease was considered. During the next 2 months (13 to 12 months before admission), two doses of rituximab were administered for persistent eye pain, blurry vision, and photophobia.
During the next 10 months (12 to 2 months before admission), the patient had monthly follow-up visits for persistent pain in both eyes and waxing and waning redness of the eyes, blurry vision, and photophobia. The treatments that were administered included pulse therapy with high-dose glucocorticoids, two additional doses of rituximab with cyclophosphamide, and cyclosporine, which caused worsening leg rashes and ulcerations. While the patient was receiving rituximab, a blood specimen was obtained for flow cytometric studies. There were 46 CD4+CD3+ T cells per cubic millimeter (reference range, 419 to 1590) and 97 CD8+CD3+ T cells per cubic millimeter (reference range, 190 to 1140). The percentage of total lymphocytes was 3%, and no B cells were detected.
Dr. Rifkin: Two months before admission, ophthalmologic examination revealed new bilateral iridocyclitis; the findings were more prominent in the left eye than the right eye. Loteprednol eyedrops and tocilizumab were administered, and the iridocyclitis resolved.
Four weeks later, the patient noticed decreased vision in her right eye. Ophthalmologic examination of the right eye revealed new panuveitis, with a cell grade of 2+ in the anterior chamber, a cell grade of 0.5+ in the anterior vitreous, and vitreous haze, as well as retinitis. Results of fluorescein angiography were normal. Loteprednol eyedrops and tocilizumab were continued. Two weeks later, ophthalmologic examination of the right eye revealed a cell grade of 3+ in the anterior chamber, a cell grade of 1+ in the anterior vitreous, a haze grade of 1+ in the vitreous, and new chorioretinitis; high-dose prednisone was administered. One week later, although the iritis and scleritis were diminishing in both eyes, there was new retinitis in the inferior aspect of the right eye (Figure 1). An intravitreal dexamethasone implant was placed, and infliximab was administered. Laboratory test results are shown in Table 1.	
Figure 1
Dr. Yokose: Three days later (6 days before admission), the patient had decreased vision in the left eye and worsened headaches, which occurred in a bifrontal distribution. These symptoms were associated with tearing, nasal pain, and nausea. In addition, a painful desquamating rash began on her lower legs and spread proximally, and it was accompanied by worsened painful peeling of her hands. The headaches and pain in her hands and legs did not respond to ibuprofen and acetaminophen. Two days before admission, the patient had decreased vision in both eyes with associated photophobia and shooting eye pain. She was admitted to the medical service of this hospital.
The patient had a 20-year history of asthma that had led to multiple hospitalizations, as well as treatment with prolonged courses of oral glucocorticoids, which were complicated by osteoporosis and hyperglycemia. She had had spontaneous pneumothoraxes in her 20s, gastroesophageal reflux disease, breast fibroadenoma and fibrocystic changes, and hypertension. Her ocular history also included meibomian gland dysfunction and aqueous tear deficiency, and she had undergone bilateral laser-assisted in situ keratomileusis (LASIK) surgery 12 years earlier. A review of systems was notable for chronic headaches, pain in the knees and elbows, mild epistaxis, and Raynaud's phenomenon. She had no fever, chills, anorexia, weight loss, confusion, seizure, vertigo, tinnitus, hearing loss, hair loss, ocular flashes or floaters, jaw claudication, nasal discharge, sinus tenderness, morning stiffness, pathergy, history of genital ulcers, skin or hair changes, or gastrointestinal or genitourinary symptoms.
Medications were prednisone, atovaquone, pantoprazole, theophylline, and valganciclovir, as well as an albuterol inhaler and nebulizer, lidocaine-diphenhydramine suspension, ibuprofen, and tramadol as needed. Eyedrops included brimonidine-timolol, latanoprost, and prednisolone. Sulfa drugs had caused anaphylaxis, cyclosporine had caused skin ulcerations, azathioprine had caused hepatotoxicity, and latex had caused bronchospasm.
The patient taught at an academic institution in New England. She had smoked cigarettes only briefly, as a teenager; she drank wine once weekly and did not use illicit drugs. She was divorced and lived with her boyfriend, with whom she was monogamous. She had a dog and had recently traveled to Nevada, where she was caught in a dust storm; she had traveled to Shanghai in the past. The patient's family was of Italian descent; her father had Crohn's disease, her mother had glaucoma and breast cancer, one sister had Hashimoto's thyroiditis, and the other sister had endometrial cancer.
The patient appeared to be uncomfortable. On examination, the temperature was 36.4[degrees]C, the heart rate 98 beats per minute, the blood pressure 157/99 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while she was breathing ambient air. The weight was 54.5 kg, the height 160 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.3. The sclerae were erythematous, and the right pupil was nonreactive to light. Neurologic examination was notable for two beats of clonus on dorsiflexion of the ankles. There were multiple aphthous ulcers on the buccal mucosal and inner surfaces of the lips, as well as linear ulcers on the tongue edges. There was an erythematous rash on the palms (Figure 2A), with desquamation, areas of healing fissures in the web spaces between the fingers, and tender erythematous papules on both upper arms. There was an erythematous, maculopapular rash on the legs (Figure 2B), with several scaled and scabbed lesions and areas of epidermal atrophy. There was bilateral inguinal lymphadenopathy. No joint erythema, tenderness, or warmth was noted. The remainder of the examination was normal.	
Figure 2 
Blood levels of electrolytes, urea nitrogen, creatinine, calcium, total protein, albumin, and globulin and results of liver-function tests were normal; other laboratory test results are shown in Table 1. Imaging studies were obtained.
Dr. Karen A. Buch: Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed no evidence of intracranial hemorrhage, mass, or acute territorial infarct; there was possible patchy hypoattenuation in the mesencephalon. Magnetic resonance imaging (MRI) of the head, including venography and arteriography, revealed no acute intracranial or intraocular abnormality, no abnormal enhancement, no thrombosis of the dural venous sinuses or deep cerebral veins, and no hemodynamically significant stenosis, occlusion, or aneurysm. There was mild dilatation of the superior ophthalmic veins that was greater on the right side than on the left side. There was no definite evidence of abnormal enhancement of the vessel wall involving the proximal major intracranial arteries. MRI of the head also revealed no focal signal abnormality or abnormal enhancement in the orbits.
Dr. Yokose: Hydromorphone, gabapentin, and ketorolac were administered for pain. The patient was urgently transferred to the eye infirmary affiliated with this hospital for ophthalmologic evaluation, which revealed normal intraocular pressures, visual acuity of 20/25 in the left eye, only light perception in the right eye, and an afferent pupillary defect in the right eye. Slit-lamp examination of the right eye revealed bilateral scleral thinning and nuclear sclerosis, a cell grade of 2+ in the anterior chamber, and a cell grade of 3+ and a haze grade of 2+ in the vitreous. Funduscopic examination revealed round, circumferential, yellow retinal lesions that were consistent with infection. Intravitreal foscarnet and ganciclovir were administered, and oral valacyclovir therapy was started. Prednisolone, latanoprost, and brimonidine-timolol eyedrops were continued.
A dose of intravenous methylprednisone was administered, and then treatment was transitioned to oral prednisone (60 mg daily). On the second day, a lumbar puncture was performed; the opening pressure was 22 cm of water, and the cerebrospinal fluid (CSF) was colorless, with a glucose level of 60 mg per deciliter (3.3 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]) and a total protein level of 160 mg per deciliter (reference range, 5 to 55). There were 64 nucleated cells per cubic millimeter (reference range, 0 to 5), of which 63% were neutrophils, 16% lymphocytes, and 21% monocytes. A punch biopsy of the rash on the left leg was performed. Treatment with clobetasol cream and tacrolimus ointment was started.
On the second and third days, the patient's temperature reached 37.3[degrees]C. Blood tests were negative for toxoplasma antibodies and for cytomegalovirus (CMV) DNA and varicella-zoster virus (VZV) DNA. CSF tests were negative for cryptococcal antigen and for human herpesvirus 6 DNA, herpes simplex virus (HSV) types 1 and 2 DNA, CMV DNA, and VZV DNA. Vitreous fluid tests were negative for toxoplasma and for HSV DNA, CMV DNA, and VZV DNA.
On the fifth day, repeat vitreous aspiration was performed with intravitreal injection of foscarnet.
On the sixth day, diagnostic test results were received
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 58-year-old woman was admitted to this hospital for vision loss in the right eye, acute progressive vision loss in the left eye, headaches, and rashes.
Four years before admission, a brown, nonpainful, nonpruritic, maculopapular rash developed on the trunk. Approximately 4 weeks later, the rash had spontaneously resolved; however, painful, peeling, erythematous papules had appeared on the hands and in the web spaces between the fingers, and oral and nasal aphthous ulcerations had occurred. During the following weeks, the hand lesions and nasal ulcers spontaneously resolved. The oral ulcers waxed and waned but continued to be present intermittently.
Dr. Lana M. Rifkin: Three and a half years before admission, bilateral temporal pingueculae were identified on routine ophthalmologic examination. Approximately 18 months later, pain and redness developed in both eyes; the patient received a diagnosis of bilateral conjunctival ulcerations, and prednisolone eyedrops were prescribed. Four weeks later, she returned to the ophthalmology clinic and reported headaches on the right side and 3 days of bilateral blurry vision, photophobia that led her to wear sunglasses indoors, and redness and pain in the right eye. She rated the eye pain as 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Bromfenac eyedrops were prescribed, and she was referred to an ophthalmologist who specialized in uveitis. Examination by the uveitis specialist revealed scleritis in the right eye and oral ulcers; prednisolone eyedrops were resumed, and oral piroxicam was prescribed.
Dr. Yokose: During the next 4 weeks, the blurry vision and photophobia decreased. Five weeks later (21 months before admission), the patient was evaluated in the rheumatology clinic of this hospital for worsened oral ulcers and recurrent blurry vision in the left eye that had developed as the glucocorticoid dose was tapered. Examination was notable for aphthous ulcers on the tongue and several nasal erosions. Blood levels of electrolytes, urea nitrogen, creatinine, calcium, total protein, albumin, and globulin and results of liver-function tests were normal. Tests for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, and anti-cyclic citrullinated peptide were negative; other laboratory test results are shown in Table 1.	
Table 1
Dr. Rifkin: One month later, the patient returned to the ophthalmology clinic for follow-up. She reported pain in the left eye (rated as 7 out of 10) and recurrent blurry vision and photophobia. Examination revealed new scleritis in the left eye.
Dr. Yokose: During the next 6 months, the patient could not be fully weaned off glucocorticoid therapy because of both chronic asthma and worsening oral ulcerations that occurred with medication tapers. Azathioprine, adalimumab, and intravitreal glucocorticoids were administered for scleritis and oral ulcers. Because testing for HLA-B51 was positive, a working diagnosis of atypical Behcet's disease was considered. During the next 2 months (13 to 12 months before admission), two doses of rituximab were administered for persistent eye pain, blurry vision, and photophobia.
During the next 10 months (12 to 2 months before admission), the patient had monthly follow-up visits for persistent pain in both eyes and waxing and waning redness of the eyes, blurry vision, and photophobia. The treatments that were administered included pulse therapy with high-dose glucocorticoids, two additional doses of rituximab with cyclophosphamide, and cyclosporine, which caused worsening leg rashes and ulcerations. While the patient was receiving rituximab, a blood specimen was obtained for flow cytometric studies. There were 46 CD4+CD3+ T cells per cubic millimeter (reference range, 419 to 1590) and 97 CD8+CD3+ T cells per cubic millimeter (reference range, 190 to 1140). The percentage of total lymphocytes was 3%, and no B cells were detected.
Dr. Rifkin: Two months before admission, ophthalmologic examination revealed new bilateral iridocyclitis; the findings were more prominent in the left eye than the right eye. Loteprednol eyedrops and tocilizumab were administered, and the iridocyclitis resolved.
Four weeks later, the patient noticed decreased vision in her right eye. Ophthalmologic examination of the right eye revealed new panuveitis, with a cell grade of 2+ in the anterior chamber, a cell grade of 0.5+ in the anterior vitreous, and vitreous haze, as well as retinitis. Results of fluorescein angiography were normal. Loteprednol eyedrops and tocilizumab were continued. Two weeks later, ophthalmologic examination of the right eye revealed a cell grade of 3+ in the anterior chamber, a cell grade of 1+ in the anterior vitreous, a haze grade of 1+ in the vitreous, and new chorioretinitis; high-dose prednisone was administered. One week later, although the iritis and scleritis were diminishing in both eyes, there was new retinitis in the inferior aspect of the right eye (Figure 1). An intravitreal dexamethasone implant was placed, and infliximab was administered. Laboratory test results are shown in Table 1.	
Figure 1
Dr. Yokose: Three days later (6 days before admission), the patient had decreased vision in the left eye and worsened headaches, which occurred in a bifrontal distribution. These symptoms were associated with tearing, nasal pain, and nausea. In addition, a painful desquamating rash began on her lower legs and spread proximally, and it was accompanied by worsened painful peeling of her hands. The headaches and pain in her hands and legs did not respond to ibuprofen and acetaminophen. Two days before admission, the patient had decreased vision in both eyes with associated photophobia and shooting eye pain. She was admitted to the medical service of this hospital.
The patient had a 20-year history of asthma that had led to multiple hospitalizations, as well as treatment with prolonged courses of oral glucocorticoids, which were complicated by osteoporosis and hyperglycemia. She had had spontaneous pneumothoraxes in her 20s, gastroesophageal reflux disease, breast fibroadenoma and fibrocystic changes, and hypertension. Her ocular history also included meibomian gland dysfunction and aqueous tear deficiency, and she had undergone bilateral laser-assisted in situ keratomileusis (LASIK) surgery 12 years earlier. A review of systems was notable for chronic headaches, pain in the knees and elbows, mild epistaxis, and Raynaud's phenomenon. She had no fever, chills, anorexia, weight loss, confusion, seizure, vertigo, tinnitus, hearing loss, hair loss, ocular flashes or floaters, jaw claudication, nasal discharge, sinus tenderness, morning stiffness, pathergy, history of genital ulcers, skin or hair changes, or gastrointestinal or genitourinary symptoms.
Medications were prednisone, atovaquone, pantoprazole, theophylline, and valganciclovir, as well as an albuterol inhaler and nebulizer, lidocaine-diphenhydramine suspension, ibuprofen, and tramadol as needed. Eyedrops included brimonidine-timolol, latanoprost, and prednisolone. Sulfa drugs had caused anaphylaxis, cyclosporine had caused skin ulcerations, azathioprine had caused hepatotoxicity, and latex had caused bronchospasm.
The patient taught at an academic institution in New England. She had smoked cigarettes only briefly, as a teenager; she drank wine once weekly and did not use illicit drugs. She was divorced and lived with her boyfriend, with whom she was monogamous. She had a dog and had recently traveled to Nevada, where she was caught in a dust storm; she had traveled to Shanghai in the past. The patient's family was of Italian descent; her father had Crohn's disease, her mother had glaucoma and breast cancer, one sister had Hashimoto's thyroiditis, and the other sister had endometrial cancer.
The patient appeared to be uncomfortable. On examination, the temperature was 36.4[degrees]C, the heart rate 98 beats per minute, the blood pressure 157/99 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while she was breathing ambient air. The weight was 54.5 kg, the height 160 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.3. The sclerae were erythematous, and the right pupil was nonreactive to light. Neurologic examination was notable for two beats of clonus on dorsiflexion of the ankles. There were multiple aphthous ulcers on the buccal mucosal and inner surfaces of the lips, as well as linear ulcers on the tongue edges. There was an erythematous rash on the palms (Figure 2A), with desquamation, areas of healing fissures in the web spaces between the fingers, and tender erythematous papules on both upper arms. There was an erythematous, maculopapular rash on the legs (Figure 2B), with several scaled and scabbed lesions and areas of epidermal atrophy. There was bilateral inguinal lymphadenopathy. No joint erythema, tenderness, or warmth was noted. The remainder of the examination was normal.	
Figure 2 
Blood levels of electrolytes, urea nitrogen, creatinine, calcium, total protein, albumin, and globulin and results of liver-function tests were normal; other laboratory test results are shown in Table 1. Imaging studies were obtained.
Dr. Karen A. Buch: Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed no evidence of intracranial hemorrhage, mass, or acute territorial infarct; there was possible patchy hypoattenuation in the mesencephalon. Magnetic resonance imaging (MRI) of the head, including venography and arteriography, revealed no acute intracranial or intraocular abnormality, no abnormal enhancement, no thrombosis of the dural venous sinuses or deep cerebral veins, and no hemodynamically significant stenosis, occlusion, or aneurysm. There was mild dilatation of the superior ophthalmic veins that was greater on the right side than on the left side. There was no definite evidence of abnormal enhancement of the vessel wall involving the proximal major intracranial arteries. MRI of the head also revealed no focal signal abnormality or abnormal enhancement in the orbits.
Dr. Yokose: Hydromorphone, gabapentin, and ketorolac were administered for pain. The patient was urgently transferred to the eye infirmary affiliated with this hospital for ophthalmologic evaluation, which revealed normal intraocular pressures, visual acuity of 20/25 in the left eye, only light perception in the right eye, and an afferent pupillary defect in the right eye. Slit-lamp examination of the right eye revealed bilateral scleral thinning and nuclear sclerosis, a cell grade of 2+ in the anterior chamber, and a cell grade of 3+ and a haze grade of 2+ in the vitreous. Funduscopic examination revealed round, circumferential, yellow retinal lesions that were consistent with infection. Intravitreal foscarnet and ganciclovir were administered, and oral valacyclovir therapy was started. Prednisolone, latanoprost, and brimonidine-timolol eyedrops were continued.
A dose of intravenous methylprednisone was administered, and then treatment was transitioned to oral prednisone (60 mg daily). On the second day, a lumbar puncture was performed; the opening pressure was 22 cm of water, and the cerebrospinal fluid (CSF) was colorless, with a glucose level of 60 mg per deciliter (3.3 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]) and a total protein level of 160 mg per deciliter (reference range, 5 to 55). There were 64 nucleated cells per cubic millimeter (reference range, 0 to 5), of which 63% were neutrophils, 16% lymphocytes, and 21% monocytes. A punch biopsy of the rash on the left leg was performed. Treatment with clobetasol cream and tacrolimus ointment was started.
On the second and third days, the patient's temperature reached 37.3[degrees]C. Blood tests were negative for toxoplasma antibodies and for cytomegalovirus (CMV) DNA and varicella-zoster virus (VZV) DNA. CSF tests were negative for cryptococcal antigen and for human herpesvirus 6 DNA, herpes simplex virus (HSV) types 1 and 2 DNA, CMV DNA, and VZV DNA. Vitreous fluid tests were negative for toxoplasma and for HSV DNA, CMV DNA, and VZV DNA.
On the fifth day, repeat vitreous aspiration was performed with intravitreal injection of foscarnet.
On the sixth day, diagnostic test results were received
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Relapsing Polychondritis. The patient's symptoms of vision loss, headaches, and rashes, along with a history of asthma, are consistent with this condition. The presence of scleritis, oral ulcers, and aphthous ulcers also point towards this diagnosis. The patient's negative tests for various infectious diseases and autoimmune conditions, along with the waxing and waning nature of her symptoms, further support this diagnosis. The patient's response to glucocorticoid therapy is also consistent with relapsing polychondritis, which is typically treated with these medications.""
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        ""content"": ""The patient's symptoms include vision loss, headaches, and rashes. She also has a history of oral and nasal aphthous ulcerations, bilateral conjunctival ulcerations, and scleritis in both eyes. The patient has been treated with various medications including glucocorticoids, azathioprine, adalimumab, and rituximab, but her symptoms have persisted. She has tested positive for HLA-B51, which is associated with Behcet's disease. However, her symptoms have not fully aligned with typical Behcet's disease, leading to a working diagnosis of atypical Behcet's disease. Despite various treatments, the patient's symptoms have continued to worsen, including new bilateral iridocyclitis and panuveitis in the right eye. The patient's symptoms and the lack of response to treatment suggest a complex and severe autoimmune condition. \n\nDiagnosis: Atypical Behcet's Disease.""
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        ""content"": ""This is a 58-year-old woman with a history of asthma, osteoporosis, and hyperglycemia who presents with vision loss in both eyes, headaches, and rashes. She has a history of bilateral conjunctival ulcerations, scleritis, and iridocyclitis. She also has a history of oral and nasal aphthous ulcerations and a maculopapular rash on the trunk. The differential diagnosis for this patient includes Behcet's disease, lupus, and other autoimmune diseases, as well as infectious diseases such as syphilis or HIV. The patient's negative tests for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, and anti-cyclic citrullinated peptide make lupus and other autoimmune diseases less likely. The patient's negative tests for HSV, CMV, and VZV also make these infectious diseases less likely. The patient's positive test for HLA-B51, along with her history of oral and nasal aphthous ulcerations, eye inflammation, and skin lesions, make Behcet's disease a likely diagnosis. However, the patient's presentation is atypical for Behcet's disease, as she does not have genital ulcers or gastrointestinal symptoms. The patient's decreased CD4+ and CD8+ T cell counts could be due to her treatment with rituximab, which depletes B cells and can indirectly affect T cell counts. However, these decreased counts could also suggest an underlying immunodeficiency. The patient's history of spontaneous pneumothoraxes in her 20s could suggest a connective tissue disorder, but her negative tests for antinuclear antibodies and rheumatoid factor make this less likely. The patient's history of LASIK surgery could potentially contribute to her eye symptoms, but this would not explain her other symptoms.\n\nDiagnosis: Atypical Behcet's disease.""
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}",Atypical Behcet's Diseas,N
10.1056/NEJMcpc1816408,Case 7-2019: A 73-Year-Old Woman with Swelling of the Right Groin and Fever,"Hematocrit (%)   29.1
Hemoglobin (g/dl)   9.4
White-cell count (per mm3)   17,900
Differential count (%)
Neutrophils   26.1
Lymphocytes   68.7
Monocytes   2.6
Eosinophils   2.6
Basophils   0
Platelet count (per mm3
)   163,000
Red-cell count (per mm3) 4,000,000–5,200,000 3,000,000
Mean corpuscular volume (fl)   97
Mean corpuscular hemoglobin (pg) 26–34 31.3
Mean corpuscular hemoglobin concentration (g/dl) 31–37 32.3
Red-cell distribution width (%)   18.5
Bilirubin (mg/dl)†
Total  1.8
Direct 0.  0.4
Lactate dehydrogenase (U/liter) 11 10 259
Alkaline phosphatase (U/liter)   92
Alanine aminotransferase (U/liter)   24
Aspartate aminotransferase (U/liter)   34",Herpes simplex virus lymphadenitis. Chronic lymphocytic leukemia.,Richter’s transformation of chronic lymphocytic leukemia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 73-year-old woman with a history of chronic lymphocytic leukemia (CLL) was admitted to this hospital because of right inguinal lymphadenopathy, fever, and drenching night sweats.
The patient had been in her usual state of health and had been undergoing active medical surveillance for CLL until 2 weeks before this presentation, when swelling of the right groin developed. During the next 2 weeks, the swollen area increased in size. Drenching night sweats and daily fevers developed; temperatures taken at home were as high as 38.3[degrees]C. The patient called her hematologist's office and was asked to present to the emergency department of this hospital for evaluation.
The patient had received a diagnosis of CLL 27 years earlier. At that time, lymphocytosis developed and an evaluation revealed pelvic lymphadenopathy. The patient underwent resection of the left ovary and a nearby retroperitoneal mass. On pathological evaluation, the ovarian tissue was normal, but findings in the nodal tissue were consistent with CLL. During the next 12 years, the patient had slowly progressive lymphocytosis and stable splenomegaly, and she underwent active surveillance with periodic complete blood counts and physical examinations.
Fifteen years before this presentation, fatigue and anemia developed and a 3-month course of chlorambucil was administered, with improvement in lymphocytosis and anemia. During the next 3 years, the patient received three additional courses of chlorambucil for symptomatic anemia, each of which was followed by a period of remission. Nine years before this presentation, anemia, thrombocytopenia, and splenomegaly developed and fludarabine and rituximab were administered, with improvement in blood counts and splenomegaly. Three years before this presentation, during post-treatment surveillance, fatigue, worsening anemia, and splenomegaly developed and idelalisib and rituximab were administered, with improvement in symptoms. After 1 year, all treatment was stopped because of a diffuse rash that was attributed to idelalisib. Two months before this presentation, the patient had a white-cell count of 19,000 per cubic millimeter (reference range, 4500 to 11,000).
In addition, several years before this presentation, hypogammaglobulinemia developed in association with rituximab treatment and was complicated by recurrent sinopulmonary infections, and intravenous immune globulin (IVIG) treatment was initiated. In the past, the patient had undergone resection of squamous-cell carcinoma from the right leg and of multiple basal-cell carcinomas. Other history included recurrent herpes simplex virus (HSV) type 1 infection of the genitals (for which she received acyclovir as needed), diverticulosis, a burst fracture of the first lumbar vertebra after a fall, and shingles due to herpes zoster infection of the right L2 dermatome. Four years before this presentation, she was treated empirically for Borrelia burgdorferi infection.
The patient had no known drug allergies. Her medications included subcutaneous IVIG every other week, a multivitamin, calcium carbonate, vitamin C, lysine, and acyclovir as needed. She had smoked tobacco for 10 years but had quit 40 years before this presentation. She drank alcohol occasionally and did not use illicit drugs. Her husband had died 1 year before this presentation, and she was not sexually active. She was a retired librarian, lived in Massachusetts, and had not traveled outside the United States. She had no pets or exposures to cats. She enjoyed gardening and took daily walks outside. Her family history included heart disease in her mother and skin cancer in her father.
In the emergency department, the patient reported ongoing daily fevers and night sweats, as well as an unspecified amount of weight loss over the past month. She reported no headaches, sore throat, cough, abdominal pain, nausea, vomiting, diarrhea, dysuria, vaginal discharge, or rash. On physical examination, the temperature was 37.4[degrees]C, the pulse 84 beats per minute, the blood pressure 140/63 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 92% while she was breathing ambient air. The weight was 61 kg, the height 158 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.7. The patient did not appear ill. The abdomen was nondistended, with normal bowel sounds and no tenderness on palpation. The spleen was palpable. Multiple right inguinal lymph nodes were enlarged, measuring 2 to 5 cm in maximal diameter; the nodes were hard, nonmobile, and mildly tender, and there were no overlying skin changes. Multiple left inguinal lymph nodes measured 1 to 2 cm in maximal diameter. There was no lymphadenopathy in the occipital, posterior auricular, anterior cervical, posterior cervical, axillary, epitrochlear, or supraclavicular region. There were no rashes or skin lesions. The remainder of the physical examination was normal.
Blood levels of electrolytes, glucose, uric acid, lactic acid, and haptoglobin were normal, as were results of renal-function tests and the prothrombin time. Urinalysis revealed clear yellow urine, with a specific gravity of 1.024 (reference range, 1.001 to 1.035) and a pH of 5.0 (reference range, 5.0 to 9.0) and with no blood, ketones, glucose, protein, nitrates, or urobilinogen. Blood cultures had no growth. Other laboratory test results are shown in Table 1. Imaging studies were obtained, and the patient was admitted to the hospital.	
Table 1 
Dr. Shahein H. Tajmir: Chest radiography revealed no consolidation or evidence of pulmonary edema. Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed multiple enlarged mediastinal and hilar lymph nodes with dystrophic calcification, as well as a nodule measuring 1 cm in diameter in the peripheral lung, abutting the pleura. There was evidence of diverticulosis, an unchanged compression fracture of the first lumbar vertebra, and stable enlargement of the spleen (measuring 24 cm in length; reference range, <=12 cm), with internal heterogeneous attenuation and scattered areas of splenic parenchymal calcification. There were multiple enlarged right inguinal lymph nodes with internal heterogeneity; the largest (dominant) lymph node measured 5 cm in diameter and had surrounding fat stranding. Right external iliac and pelvic sidewall lymph nodes measured up to 4 cm in diameter, and left pelvic sidewall lymph nodes were also enlarged.
Assessment of the area from the neck to the proximal thigh with the use of 18F-fluorodeoxyglucose (FDG)-positron-emission tomography and CT (PET-CT) revealed intense FDG uptake in the right inguinal lymph nodes, approximately three times the uptake in the liver (Figure 1). The dominant node had central photopenia suggestive of necrosis. Right external iliac and pelvic sidewall lymph nodes had moderate FDG uptake, greater than the uptake in the liver. In the chest, a high right paratracheal lymph node had moderate FDG uptake, slightly greater than the uptake in the liver, and a subpleural nodule in the left upper lobe had mild FDG uptake. The level of FDG uptake in the spleen was lower than the level in the liver, with no focal uptake abnormality.	
Figure 1 
Dr. Maurer: On the second hospital day, fine-needle aspiration and core biopsy of the dominant right inguinal lymph node were performed.
Dr. Lucas R. Massoth: Examination of the core biopsy specimen revealed a dense monomorphic infiltrate of small mature lymphocytes with scant cytoplasm (Figure 2A). Some areas of the tumor were necrotic, but there was no evidence of large-cell transformation (Figure 2B). Flow cytometry and immunohistochemical staining revealed monoclonal B cells that had an immunophenotype characteristic of CLL (Figure 2C and 2D).	
Figure 2 
Dr. Maurer: Additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 73-year-old woman with a history of chronic lymphocytic leukemia (CLL) was admitted to this hospital because of right inguinal lymphadenopathy, fever, and drenching night sweats.
The patient had been in her usual state of health and had been undergoing active medical surveillance for CLL until 2 weeks before this presentation, when swelling of the right groin developed. During the next 2 weeks, the swollen area increased in size. Drenching night sweats and daily fevers developed; temperatures taken at home were as high as 38.3[degrees]C. The patient called her hematologist's office and was asked to present to the emergency department of this hospital for evaluation.
The patient had received a diagnosis of CLL 27 years earlier. At that time, lymphocytosis developed and an evaluation revealed pelvic lymphadenopathy. The patient underwent resection of the left ovary and a nearby retroperitoneal mass. On pathological evaluation, the ovarian tissue was normal, but findings in the nodal tissue were consistent with CLL. During the next 12 years, the patient had slowly progressive lymphocytosis and stable splenomegaly, and she underwent active surveillance with periodic complete blood counts and physical examinations.
Fifteen years before this presentation, fatigue and anemia developed and a 3-month course of chlorambucil was administered, with improvement in lymphocytosis and anemia. During the next 3 years, the patient received three additional courses of chlorambucil for symptomatic anemia, each of which was followed by a period of remission. Nine years before this presentation, anemia, thrombocytopenia, and splenomegaly developed and fludarabine and rituximab were administered, with improvement in blood counts and splenomegaly. Three years before this presentation, during post-treatment surveillance, fatigue, worsening anemia, and splenomegaly developed and idelalisib and rituximab were administered, with improvement in symptoms. After 1 year, all treatment was stopped because of a diffuse rash that was attributed to idelalisib. Two months before this presentation, the patient had a white-cell count of 19,000 per cubic millimeter (reference range, 4500 to 11,000).
In addition, several years before this presentation, hypogammaglobulinemia developed in association with rituximab treatment and was complicated by recurrent sinopulmonary infections, and intravenous immune globulin (IVIG) treatment was initiated. In the past, the patient had undergone resection of squamous-cell carcinoma from the right leg and of multiple basal-cell carcinomas. Other history included recurrent herpes simplex virus (HSV) type 1 infection of the genitals (for which she received acyclovir as needed), diverticulosis, a burst fracture of the first lumbar vertebra after a fall, and shingles due to herpes zoster infection of the right L2 dermatome. Four years before this presentation, she was treated empirically for Borrelia burgdorferi infection.
The patient had no known drug allergies. Her medications included subcutaneous IVIG every other week, a multivitamin, calcium carbonate, vitamin C, lysine, and acyclovir as needed. She had smoked tobacco for 10 years but had quit 40 years before this presentation. She drank alcohol occasionally and did not use illicit drugs. Her husband had died 1 year before this presentation, and she was not sexually active. She was a retired librarian, lived in Massachusetts, and had not traveled outside the United States. She had no pets or exposures to cats. She enjoyed gardening and took daily walks outside. Her family history included heart disease in her mother and skin cancer in her father.
In the emergency department, the patient reported ongoing daily fevers and night sweats, as well as an unspecified amount of weight loss over the past month. She reported no headaches, sore throat, cough, abdominal pain, nausea, vomiting, diarrhea, dysuria, vaginal discharge, or rash. On physical examination, the temperature was 37.4[degrees]C, the pulse 84 beats per minute, the blood pressure 140/63 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 92% while she was breathing ambient air. The weight was 61 kg, the height 158 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 24.7. The patient did not appear ill. The abdomen was nondistended, with normal bowel sounds and no tenderness on palpation. The spleen was palpable. Multiple right inguinal lymph nodes were enlarged, measuring 2 to 5 cm in maximal diameter; the nodes were hard, nonmobile, and mildly tender, and there were no overlying skin changes. Multiple left inguinal lymph nodes measured 1 to 2 cm in maximal diameter. There was no lymphadenopathy in the occipital, posterior auricular, anterior cervical, posterior cervical, axillary, epitrochlear, or supraclavicular region. There were no rashes or skin lesions. The remainder of the physical examination was normal.
Blood levels of electrolytes, glucose, uric acid, lactic acid, and haptoglobin were normal, as were results of renal-function tests and the prothrombin time. Urinalysis revealed clear yellow urine, with a specific gravity of 1.024 (reference range, 1.001 to 1.035) and a pH of 5.0 (reference range, 5.0 to 9.0) and with no blood, ketones, glucose, protein, nitrates, or urobilinogen. Blood cultures had no growth. Other laboratory test results are shown in Table 1. Imaging studies were obtained, and the patient was admitted to the hospital.	
Table 1 
Dr. Shahein H. Tajmir: Chest radiography revealed no consolidation or evidence of pulmonary edema. Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed multiple enlarged mediastinal and hilar lymph nodes with dystrophic calcification, as well as a nodule measuring 1 cm in diameter in the peripheral lung, abutting the pleura. There was evidence of diverticulosis, an unchanged compression fracture of the first lumbar vertebra, and stable enlargement of the spleen (measuring 24 cm in length; reference range, <=12 cm), with internal heterogeneous attenuation and scattered areas of splenic parenchymal calcification. There were multiple enlarged right inguinal lymph nodes with internal heterogeneity; the largest (dominant) lymph node measured 5 cm in diameter and had surrounding fat stranding. Right external iliac and pelvic sidewall lymph nodes measured up to 4 cm in diameter, and left pelvic sidewall lymph nodes were also enlarged.
Assessment of the area from the neck to the proximal thigh with the use of 18F-fluorodeoxyglucose (FDG)-positron-emission tomography and CT (PET-CT) revealed intense FDG uptake in the right inguinal lymph nodes, approximately three times the uptake in the liver (Figure 1). The dominant node had central photopenia suggestive of necrosis. Right external iliac and pelvic sidewall lymph nodes had moderate FDG uptake, greater than the uptake in the liver. In the chest, a high right paratracheal lymph node had moderate FDG uptake, slightly greater than the uptake in the liver, and a subpleural nodule in the left upper lobe had mild FDG uptake. The level of FDG uptake in the spleen was lower than the level in the liver, with no focal uptake abnormality.	
Figure 1 
Dr. Maurer: On the second hospital day, fine-needle aspiration and core biopsy of the dominant right inguinal lymph node were performed.
Dr. Lucas R. Massoth: Examination of the core biopsy specimen revealed a dense monomorphic infiltrate of small mature lymphocytes with scant cytoplasm (Figure 2A). Some areas of the tumor were necrotic, but there was no evidence of large-cell transformation (Figure 2B). Flow cytometry and immunohistochemical staining revealed monoclonal B cells that had an immunophenotype characteristic of CLL (Figure 2C and 2D).	
Figure 2 
Dr. Maurer: Additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Richter's transformation of chronic lymphocytic leukemia. The patient's history of CLL, along with the recent development of fever, night sweats, and rapidly enlarging lymph nodes, suggests a transformation to a more aggressive lymphoma. This is supported by the PET-CT findings of intense FDG uptake in the right inguinal lymph nodes and moderate uptake in the right external iliac and pelvic sidewall lymph nodes. The biopsy of the right inguinal lymph node confirmed the presence of a dense monomorphic infiltrate of small mature lymphocytes, characteristic of CLL, but the rapid progression of symptoms and the PET-CT findings suggest a transformation to a more aggressive form of lymphoma, known as Richter's transformation.""
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        ""content"": ""The patient has a history of chronic lymphocytic leukemia (CLL) and presents with right inguinal lymphadenopathy, fever, and night sweats. The lymphadenopathy is associated with fever and night sweats, which are symptoms of B symptoms, indicating a systemic manifestation of the disease. The patient's history of CLL and the presence of these symptoms suggest that the CLL has progressed. The biopsy of the lymph node confirms the presence of CLL. Therefore, the final diagnosis is progression of chronic lymphocytic leukemia.""
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        ""content"": ""The patient is a 73-year-old woman with a history of chronic lymphocytic leukemia (CLL) presenting with right inguinal lymphadenopathy, fever, and drenching night sweats. The differential diagnosis for this patient includes CLL progression, Richter's transformation, infection, and lymphoma. The patient's history of CLL and the recent increase in lymphadenopathy and systemic symptoms such as fever and night sweats suggest disease progression or transformation. Richter's transformation, which is a transformation of CLL into a more aggressive lymphoma, often presents with rapidly enlarging lymph nodes, B symptoms (fever, night sweats, weight loss), and elevated LDH, which fits this patient's presentation. However, the patient's history of hypogammaglobulinemia and recurrent infections also raises the possibility of an infectious process. Lymphoma could also present with lymphadenopathy and B symptoms, but the patient's long history of CLL makes this less likely. The biopsy of the lymph node showed a dense monomorphic infiltrate of small mature lymphocytes with scant cytoplasm, which is consistent with CLL, and there was no evidence of large-cell transformation, making Richter's transformation less likely. Therefore, the most likely diagnosis is progression of CLL.\n\nDiagnosis: Progression of chronic lymphocytic leukemia.""
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10.1056/NEJMcpc1816407,"Case 6-2019: A 29-Year-Old Woman with Nausea, Vomiting, and Diarrhea",,Oxycodone and cocaine use.,Severe opioid use disorder.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-year-old woman was evaluated at a primary care clinic affiliated with this hospital because of nausea, vomiting, and diarrhea.
The patient had been in her usual state of good health until the day before presentation, when nausea, vomiting, diarrhea, fever, muscle aches, and a mild nonproductive cough developed suddenly. She had no sinus congestion, sore throat, shortness of breath, or abdominal pain. Over the telephone on the morning before presentation, she reported that her symptoms were severe and had prevented her from attending work. However, when she was evaluated later in the day by a provider at her primary care clinic, she reported that she had had spontaneous improvement in the morning and felt well on arrival at the clinic.
The patient had a history of exercise-induced asthma, gastroesophageal reflux disease, vitiligo, and genital warts. Two years before presentation, she had had negative screening tests for hepatitis C virus and human immunodeficiency virus. Fifteen months before presentation, she had received a diagnosis of influenza. During the months that followed, she had reported persistent bouts of fatigue and excessive sleepiness that had resulted in two motor vehicle accidents.
During the first event, which had occurred 13 months before presentation, the patient fell asleep while driving and her car crossed into the other lane, over the curb, and into an open space beside the road. She did not collide with any other vehicles or structures and had no trauma. During the second event, which had occurred 7 months before presentation, the patient collided with a turning vehicle. She did not lose consciousness, and the airbags did not deploy. After the crash, she had intermittent painful episodes of muscle spasms in her neck and low back that limited her range of motion. She was too fatigued to seek medical attention until the day after the collision.
The patient subsequently underwent evaluation at her primary care clinic. Her score on the Epworth Sleepiness Scale was 20, with scores ranging from 0 (low-normal daytime sleepiness) to 24 (excessive daytime sleepiness). She was referred for a formal sleep study. In addition, she received prescriptions for naproxen and cyclobenzaprine and completed outpatient physical therapy, and her muscle spasms diminished.
The patient had not undergone any surgical procedures. Medications included omeprazole, varenicline, naproxen, and cyclobenzaprine. Hydrocodone-acetaminophen had caused nausea. The patient was adopted, and her family history was unknown. She lived in an urban neighborhood in New England with her daughter, brother, and sister. She worked two full-time jobs, as a school counselor and a bartender. She smoked one pack of cigarettes weekly and had done so for 17 years, and she reportedly drank two to three alcoholic beverages weekly.
On physical examination, the temperature was 36.8[degrees]C, the pulse 106 beats per minute, and the blood pressure 117/91 mm Hg. The weight was 63.5 kg, the height 170 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.9. The patient appeared to be well. She had no diaphoresis or rashes, needle marks, or scars. The pupils were equal and reactive, the mucous membranes were moist, and the abdomen was soft, with no tenderness on palpation. Results of liver-function tests were normal, and testing for urinary human chorionic gonadotropin was negative.
Just before the conclusion of the office visit, the patient reported a history of use of nonprescribed oxycodone-acetaminophen tablets and requested initiation of therapy with injectable intramuscular naltrexone. Urine toxicology screening was ordered, and oral naltrexone was prescribed. A follow-up visit was planned for 6 days later, but the patient did not complete the urine toxicology screening or return to the clinic for her scheduled follow-up. However, 2 months later, she requested a referral for psychotherapy because of increased symptoms of stress.
Four months after she requested the referral and 6 months after presentation, the patient was seen in the outpatient psychology clinic of this hospital, where additional history was obtained. She reported poor sleep, low energy, loss of interest in enjoyable activities, feelings of guilt, increased appetite, and a sensation that her legs were heavy and difficult to move. She also reported intermittent episodes of heightened energy, pressured speech, racing thoughts, and excessive spending. She had no history of hallucinations or thoughts of harming herself or others.
At the psychology clinic, the patient reported that she had begun to use illicit drugs - including marijuana, oral opioids, cocaine, and 3,4-methylenedioxymethamphetamine - when she was in middle school. She had continued to use multiple substances for 5 years but had abruptly discontinued when she became pregnant, at 19 years of age. She did not use illicit drugs for 8 years after the birth of her daughter but then resumed regular use of oral opioids 3 years before presentation, when she began to work at a bar where drugs were frequently available. Since then, she had used escalating amounts of oral oxycodone to satisfy increased cravings and prevent withdrawal symptoms.
The patient reported that she used 120 mg of oxycodone per day and spent approximately $3000 per month on oxycodone. She had missed work because of withdrawal symptoms, and she worried that she would lose custody of her daughter because of her drug use. She had never been hospitalized for opioid use or had an overdose. On several occasions, she had used nonprescribed buprenorphine, which had alleviated her withdrawal symptoms and cravings, but she had never tried buprenorphine treatment that had been prescribed by a health care provider. In addition, on several occasions, she had tried to initiate treatment with injectable intramuscular naltrexone but had been unable to abstain from opioid use long enough to receive the treatment. A plan was made for the patient to continue with outpatient cognitive behavioral therapy and mindfulness exercises, and a follow-up visit with her primary care physician was scheduled.
One month later, the patient was seen by her primary care physician. Oral-fluid toxicology screening was positive for oxycodone, buprenorphine, benzoylecgonine, and cocaine; testing of the saliva was negative for fentanyl. A diagnosis and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-year-old woman was evaluated at a primary care clinic affiliated with this hospital because of nausea, vomiting, and diarrhea.
The patient had been in her usual state of good health until the day before presentation, when nausea, vomiting, diarrhea, fever, muscle aches, and a mild nonproductive cough developed suddenly. She had no sinus congestion, sore throat, shortness of breath, or abdominal pain. Over the telephone on the morning before presentation, she reported that her symptoms were severe and had prevented her from attending work. However, when she was evaluated later in the day by a provider at her primary care clinic, she reported that she had had spontaneous improvement in the morning and felt well on arrival at the clinic.
The patient had a history of exercise-induced asthma, gastroesophageal reflux disease, vitiligo, and genital warts. Two years before presentation, she had had negative screening tests for hepatitis C virus and human immunodeficiency virus. Fifteen months before presentation, she had received a diagnosis of influenza. During the months that followed, she had reported persistent bouts of fatigue and excessive sleepiness that had resulted in two motor vehicle accidents.
During the first event, which had occurred 13 months before presentation, the patient fell asleep while driving and her car crossed into the other lane, over the curb, and into an open space beside the road. She did not collide with any other vehicles or structures and had no trauma. During the second event, which had occurred 7 months before presentation, the patient collided with a turning vehicle. She did not lose consciousness, and the airbags did not deploy. After the crash, she had intermittent painful episodes of muscle spasms in her neck and low back that limited her range of motion. She was too fatigued to seek medical attention until the day after the collision.
The patient subsequently underwent evaluation at her primary care clinic. Her score on the Epworth Sleepiness Scale was 20, with scores ranging from 0 (low-normal daytime sleepiness) to 24 (excessive daytime sleepiness). She was referred for a formal sleep study. In addition, she received prescriptions for naproxen and cyclobenzaprine and completed outpatient physical therapy, and her muscle spasms diminished.
The patient had not undergone any surgical procedures. Medications included omeprazole, varenicline, naproxen, and cyclobenzaprine. Hydrocodone-acetaminophen had caused nausea. The patient was adopted, and her family history was unknown. She lived in an urban neighborhood in New England with her daughter, brother, and sister. She worked two full-time jobs, as a school counselor and a bartender. She smoked one pack of cigarettes weekly and had done so for 17 years, and she reportedly drank two to three alcoholic beverages weekly.
On physical examination, the temperature was 36.8[degrees]C, the pulse 106 beats per minute, and the blood pressure 117/91 mm Hg. The weight was 63.5 kg, the height 170 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.9. The patient appeared to be well. She had no diaphoresis or rashes, needle marks, or scars. The pupils were equal and reactive, the mucous membranes were moist, and the abdomen was soft, with no tenderness on palpation. Results of liver-function tests were normal, and testing for urinary human chorionic gonadotropin was negative.
Just before the conclusion of the office visit, the patient reported a history of use of nonprescribed oxycodone-acetaminophen tablets and requested initiation of therapy with injectable intramuscular naltrexone. Urine toxicology screening was ordered, and oral naltrexone was prescribed. A follow-up visit was planned for 6 days later, but the patient did not complete the urine toxicology screening or return to the clinic for her scheduled follow-up. However, 2 months later, she requested a referral for psychotherapy because of increased symptoms of stress.
Four months after she requested the referral and 6 months after presentation, the patient was seen in the outpatient psychology clinic of this hospital, where additional history was obtained. She reported poor sleep, low energy, loss of interest in enjoyable activities, feelings of guilt, increased appetite, and a sensation that her legs were heavy and difficult to move. She also reported intermittent episodes of heightened energy, pressured speech, racing thoughts, and excessive spending. She had no history of hallucinations or thoughts of harming herself or others.
At the psychology clinic, the patient reported that she had begun to use illicit drugs - including marijuana, oral opioids, cocaine, and 3,4-methylenedioxymethamphetamine - when she was in middle school. She had continued to use multiple substances for 5 years but had abruptly discontinued when she became pregnant, at 19 years of age. She did not use illicit drugs for 8 years after the birth of her daughter but then resumed regular use of oral opioids 3 years before presentation, when she began to work at a bar where drugs were frequently available. Since then, she had used escalating amounts of oral oxycodone to satisfy increased cravings and prevent withdrawal symptoms.
The patient reported that she used 120 mg of oxycodone per day and spent approximately $3000 per month on oxycodone. She had missed work because of withdrawal symptoms, and she worried that she would lose custody of her daughter because of her drug use. She had never been hospitalized for opioid use or had an overdose. On several occasions, she had used nonprescribed buprenorphine, which had alleviated her withdrawal symptoms and cravings, but she had never tried buprenorphine treatment that had been prescribed by a health care provider. In addition, on several occasions, she had tried to initiate treatment with injectable intramuscular naltrexone but had been unable to abstain from opioid use long enough to receive the treatment. A plan was made for the patient to continue with outpatient cognitive behavioral therapy and mindfulness exercises, and a follow-up visit with her primary care physician was scheduled.
One month later, the patient was seen by her primary care physician. Oral-fluid toxicology screening was positive for oxycodone, buprenorphine, benzoylecgonine, and cocaine; testing of the saliva was negative for fentanyl. A diagnosis and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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10.1056/NEJMcpc1807495,Case 5-2019: A 48-Year-Old Woman with Delusional Thinking and Paresthesia of the Right Hand,"Sodium (mmol/liter)   140
Potassium (mmol/liter)   3.3
Chloride (mmol/liter)   104
Carbon dioxide (mmol/liter)   25
Glucose (mg/dl)   88
Urea nitrogen (mg/dl)   12
Creatinine (mg/dl)   0.63
Calcium (mg/dl)   8.9
Alkaline phosphatase (U/liter)   97
Bilirubin (mg/dl)
Total 0–1.0 0.2
Direct   <0.2
Alanine aminotransferase (U/liter)   97
Aspartate aminotransferase (U/liter)   24
Protein (g/dl)
Total 6. .3 6.7
Albumin   4.4
Globulin   2.3
Ammonia (μmol/liter) 12–48 50
Antitreponemal antibody Negative Negative
Creatine kinase (U/liter)   247
Erythrocyte sedimentation rate 
(mm/hr)
 0 12
Lactate (mmol/liter)   1.3
Lactate dehydrogenase (U/liter) 11 10 325
Phosphorus (mg/dl)   2.9
Prolactin (ng/ml) 0.1–23.3 41.2
Thyrotropin (μIU/ml) 0.4–5.0 1.28
Vitamin B1 (nmol/liter) 70–180 96
Hematocrit (%)   32.1
Hemoglobin (g/dl)   10.0
White-cell count (per mm3)   3130
Differential count (%)
Neutrophils   33.2
Lymphocytes   39.3
Monocytes   13.1
Eosinophils   14.1
Basophils   0.3
Platelet count (per mm3
)   326,000
Red-cell count (per mm3
) 4,000,000–
5,900,000
3,390,000
Mean corpuscular volume (fl)   82.3
Red-cell distribution width (%)   20.4",Pernicious anemia (vitamin B12 deficiency),"Vitamin B12 (cobalamin) deficiency.

Probable schizophrenia.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old woman presented to the emergency department of this hospital with tingling of the right hand.
One hour before presentation, the patient felt an acute ""prickling and tingling"" sensation diffusely on the right palm while she was reaching for a can of soda out of a vending machine. The sensation did not radiate to other areas of the hand or the arm, and it was not associated with decreased range of motion, tenderness, or joint pain. Although she presented to the emergency department 1 hour after the onset of symptoms, the tingling resolved before the examination, which took place approximately 80 minutes after presentation. The patient stated that she had recently traveled to Boston from New York City to visit museums, and she requested ""accommodations"" from medical personnel because she did not have a place to stay.
On examination, the temperature was 36.9[degrees]C, the blood pressure 141/89 mm Hg, the heart rate 88 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The weight was 70.9 kg, the height 160 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 27.7. The patient was described as having a labile affect, with rapid and tangential speech. The results of the remainder of the physical examination, including tests of neurologic function and examination of the muscles in the right hand and arm, were normal. The patient was discharged from the emergency department with a list of local shelters and hotels.
Five hours after discharge, the patient felt recurrent tingling on the right palm, primarily along the radial-nerve distribution, and she again presented to the emergency department of this hospital. She reported that she had been unable to find a shelter and that she feared hotel staff would perform ""unwanted sleep studies"" or ""gas"" her. The results of the physical examination had not changed from several hours earlier. The patient was described as disheveled, unkempt, malodorous, and oriented to person and time. Examination revealed inconsistent thought processes and delusions of persecution. Urine toxicology screening was negative for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, and phencyclidine, and serum toxicology screening was negative for salicylates, acetaminophen, ethanol, and tricyclic antidepressants. A urine test for human chorionic gonadotropin was negative. Laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
Dr. Brent P. Little: A radiograph of the right hand and wrist (Figure 1) showed no acute fracture, dislocation, or soft-tissue abnormality; the joint spaces were preserved, and there were no joint erosions. Computed tomography (CT) of the head (Figure 2), performed without the administration of intravenous contrast material, revealed no evidence of intracranial hemorrhage, mass, or acute territorial infarct.	
Figure 1 
Dr. Crall: On evaluation by a psychiatrist, the patient incorrectly named the city and state as ""Massatution"" and ""Boston,"" respectively. Mental-status examination was notable for attentiveness to the interviewer, recall of two of five objects after 5 minutes, and the inability to subtract serial sevens and to repeat phrases. The patient's score on the Montreal Cognitive Assessment was 21 (reference range, 26 to 30) on a scale of 0 to 30, with lower scores indicating greater cognitive impairment. She maintained eye contact and had no abnormal movements. Her speech was characterized by malapropisms and mispronunciations and was pressured. Her mood was described as happy, with a congruent affect. Her thought processes were described as tangential and disorganized. The results of the neurologic examination, including tests of cranial-nerve function, strength, and sensation to light touch, were normal.
The patient reported no history of medical problems. She said that she had previously been a ""volunteer client"" at a psychiatric hospital in New York City but had not undergone psychiatric treatments or hospitalizations. A review of systems was negative for physical trauma, anorexia, weight loss, loss of energy, weakness, bleeding (menstrual cycles had stopped during the past year), headache, ataxia, dizziness, seizure, syncope, pain, depression, anhedonia, expansive mood, distractibility, anxiety, memory difficulties, sleep disturbance, auditory and visual hallucinations, suicidal ideation, and homicidal ideation. She took no medications and had no known allergies to medications.
The patient reported the following information. She was born in the southeastern United States and grew up in an orphanage. She had skipped grades in elementary and high school because of high intelligence and then had obtained doctoral degrees in psychology from ""Northwestern International University in Denmark"" and ""Panworld University in China."" Six years earlier, she had moved to New York City, where she lived in a downtown hotel. She was employed as a scientist to perform online research and volunteered for New York City hospitals and the U.S. Navy. She was unmarried and had no children, and she had no family or friends who could provide collateral information. She did not use alcohol, tobacco, or illicit drugs. Her family psychiatric and medical history was unknown, since she was adopted. She had no history of legal problems.
Because of concern about the patient's inability to protect herself in a new environment, given her impaired judgment and disorganized thinking, an order that authorized temporary involuntary hospitalization was implemented.1 The patient was admitted to the inpatient psychiatry unit. Results of urinalysis and the venous blood pH were normal; laboratory test results are shown in Table 1. Additional imaging studies were obtained.
Dr. Little: A chest radiograph showed clear lungs. Magnetic resonance imaging (MRI) of the head (Figure 2), performed without the administration of intravenous contrast material, revealed mild mucosal thickening in the paranasal sinus without acute intracranial abnormality. There was no evidence of infarct, such as intracranial mass, cerebral edema, or restricted diffusion, and there was no evidence of white-matter disease or volume loss.
Dr. Crall: Laboratory test results that were obtained on the third hospital day are shown in Table 1. Results of additional diagnostic tests were received.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old woman presented to the emergency department of this hospital with tingling of the right hand.
One hour before presentation, the patient felt an acute ""prickling and tingling"" sensation diffusely on the right palm while she was reaching for a can of soda out of a vending machine. The sensation did not radiate to other areas of the hand or the arm, and it was not associated with decreased range of motion, tenderness, or joint pain. Although she presented to the emergency department 1 hour after the onset of symptoms, the tingling resolved before the examination, which took place approximately 80 minutes after presentation. The patient stated that she had recently traveled to Boston from New York City to visit museums, and she requested ""accommodations"" from medical personnel because she did not have a place to stay.
On examination, the temperature was 36.9[degrees]C, the blood pressure 141/89 mm Hg, the heart rate 88 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The weight was 70.9 kg, the height 160 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 27.7. The patient was described as having a labile affect, with rapid and tangential speech. The results of the remainder of the physical examination, including tests of neurologic function and examination of the muscles in the right hand and arm, were normal. The patient was discharged from the emergency department with a list of local shelters and hotels.
Five hours after discharge, the patient felt recurrent tingling on the right palm, primarily along the radial-nerve distribution, and she again presented to the emergency department of this hospital. She reported that she had been unable to find a shelter and that she feared hotel staff would perform ""unwanted sleep studies"" or ""gas"" her. The results of the physical examination had not changed from several hours earlier. The patient was described as disheveled, unkempt, malodorous, and oriented to person and time. Examination revealed inconsistent thought processes and delusions of persecution. Urine toxicology screening was negative for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, and phencyclidine, and serum toxicology screening was negative for salicylates, acetaminophen, ethanol, and tricyclic antidepressants. A urine test for human chorionic gonadotropin was negative. Laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
Dr. Brent P. Little: A radiograph of the right hand and wrist (Figure 1) showed no acute fracture, dislocation, or soft-tissue abnormality; the joint spaces were preserved, and there were no joint erosions. Computed tomography (CT) of the head (Figure 2), performed without the administration of intravenous contrast material, revealed no evidence of intracranial hemorrhage, mass, or acute territorial infarct.	
Figure 1 
Dr. Crall: On evaluation by a psychiatrist, the patient incorrectly named the city and state as ""Massatution"" and ""Boston,"" respectively. Mental-status examination was notable for attentiveness to the interviewer, recall of two of five objects after 5 minutes, and the inability to subtract serial sevens and to repeat phrases. The patient's score on the Montreal Cognitive Assessment was 21 (reference range, 26 to 30) on a scale of 0 to 30, with lower scores indicating greater cognitive impairment. She maintained eye contact and had no abnormal movements. Her speech was characterized by malapropisms and mispronunciations and was pressured. Her mood was described as happy, with a congruent affect. Her thought processes were described as tangential and disorganized. The results of the neurologic examination, including tests of cranial-nerve function, strength, and sensation to light touch, were normal.
The patient reported no history of medical problems. She said that she had previously been a ""volunteer client"" at a psychiatric hospital in New York City but had not undergone psychiatric treatments or hospitalizations. A review of systems was negative for physical trauma, anorexia, weight loss, loss of energy, weakness, bleeding (menstrual cycles had stopped during the past year), headache, ataxia, dizziness, seizure, syncope, pain, depression, anhedonia, expansive mood, distractibility, anxiety, memory difficulties, sleep disturbance, auditory and visual hallucinations, suicidal ideation, and homicidal ideation. She took no medications and had no known allergies to medications.
The patient reported the following information. She was born in the southeastern United States and grew up in an orphanage. She had skipped grades in elementary and high school because of high intelligence and then had obtained doctoral degrees in psychology from ""Northwestern International University in Denmark"" and ""Panworld University in China."" Six years earlier, she had moved to New York City, where she lived in a downtown hotel. She was employed as a scientist to perform online research and volunteered for New York City hospitals and the U.S. Navy. She was unmarried and had no children, and she had no family or friends who could provide collateral information. She did not use alcohol, tobacco, or illicit drugs. Her family psychiatric and medical history was unknown, since she was adopted. She had no history of legal problems.
Because of concern about the patient's inability to protect herself in a new environment, given her impaired judgment and disorganized thinking, an order that authorized temporary involuntary hospitalization was implemented.1 The patient was admitted to the inpatient psychiatry unit. Results of urinalysis and the venous blood pH were normal; laboratory test results are shown in Table 1. Additional imaging studies were obtained.
Dr. Little: A chest radiograph showed clear lungs. Magnetic resonance imaging (MRI) of the head (Figure 2), performed without the administration of intravenous contrast material, revealed mild mucosal thickening in the paranasal sinus without acute intracranial abnormality. There was no evidence of infarct, such as intracranial mass, cerebral edema, or restricted diffusion, and there was no evidence of white-matter disease or volume loss.
Dr. Crall: Laboratory test results that were obtained on the third hospital day are shown in Table 1. Results of additional diagnostic tests were received.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 48-year-old woman who presented with tingling in the right hand, which resolved before examination. She also exhibited signs of disorganized thinking, delusions of persecution, and cognitive impairment. The differential diagnosis for this patient includes neurological conditions such as transient ischemic attack or peripheral neuropathy, psychiatric conditions such as schizophrenia or bipolar disorder, and metabolic conditions such as hypoglycemia or electrolyte imbalance. However, the patient's neurological examination was normal, and her symptoms did not improve with time, making a transient ischemic attack unlikely. Peripheral neuropathy typically presents with a more chronic course and would not explain her psychiatric symptoms. Her laboratory results did not indicate a metabolic disorder. The patient's disorganized thinking, delusions of persecution, and cognitive impairment are suggestive of a psychiatric condition. Given her age, the sudden onset of her symptoms, and the absence of a previous psychiatric history, a diagnosis of late-onset schizophrenia is less likely. The patient's pressured speech, tangential thought processes, and happy mood could suggest a manic episode of bipolar disorder, but she did not report previous depressive or manic episodes. The patient's cognitive impairment, disorganized thinking, and delusions of persecution are most consistent with a delirium. Delirium can be caused by a variety of conditions, including infections, metabolic disorders, and drug intoxication or withdrawal. However, her laboratory results did not indicate an infection or metabolic disorder, and her urine toxicology screen was negative. The patient's cognitive impairment, disorganized thinking, and delusions of persecution, in the absence of a clear physical cause, suggest a diagnosis of a functional psychiatric disorder, such as a brief psychotic disorder.\n\nDiagnosis: Brief Psychotic Disorder.""
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10.1056/NEJMcpc1810391,Case 4-2019: An 18-Year-Old Man with Abdominal Pain and Hematochezia,"Hematocrit (%)  39.8 40.0–53.0 39.2   35.1 27.6 27.7
Hemoglobin (g/dl)   12.6  12.7   11.4 9.2 9.1
White-cell count (per mm3) 450 ,500 8900 400 ,000 9900 450 ,000 5420 2560 5950
Differential count (%)
Neutrophils  72.4 88 40–62 78.1 63.5
Immature granulocytes  0.1
Bands 0–10 9.6 6.9                                                                                                         Metamyelocytes 0 0.9
Lymphocytes  19.0 6 9.6 29.6
Monocytes 2. .0 6.1 5   1.8 0
Eosinophils 1. .0 2.2 0   0 0
Basophils  0.2 0   0 0
Platelet count (per mm3)   184,000 130,000–450,000 257,000   99,000 79,000 74,000
Red-cell count (per mm3) 5,490,000 5,570,000 4,500,000–
5,900,000
5,150,000 4,160,000 4,120,000
Mean corpuscular volume (fl)  72.5 78–100 70   68.2 66.3 63.8
Mean corpuscular hemoglobin (pg) 26. 2.0 23.0 27. 4.0 22.8 26. 4.0 22.1 22.1 21.7
Description of peripheral-blood smear Toxic granulation, 
vacuolated neutro‚Äë
phils, Döhle bod‑
ies, Burr cells, ellip‚Äë
tocytes, target cells, 
large platelets, 1+ 
polychromasia                                                                                                               Urea nitrogen (mg/dl) 7–21 15   14   17 13
Creatinine (mg/dl) 0.7–1.3 1.1 0.60–1.20 1.18   1.38 1.18
Glucose (mg/dl) 74–106 89 6 9 114   130 96
Alanine aminotransferase (U/liter) 12–78 36 10–41 15   44 36 49
Aspartate aminotransferase (U/liter) 15–37 57 10–50 19   65 48 69
Protein (g/dl)
Total 6.4–8.2 7.5 6. .0 8.1 6. .3 7.1 5.7 6.6                                                   Albumin   3.7   3.9   3.3 2.9 3.2
Globulin   3.8 2.8 3.4
Erythrocyte sedimentation rate 
(mm/hr)
  41   40
C-reactive protein (mg/liter) 2. .0 103.1  .0 281.6
Prothrombin time (sec)   15.8   16.1 15.1 15.1
Prothrombin-time international 
normalized ratio
  1.4   1.3 1.2 1.2
Activated partial-thromboplastin time 
(sec)
24. 6.5 33.9 22. 5.0 37.2 35.6 35.9
d-Dimer (ng/ml)   >10,000                                                                                  Fibrinogen (ng/ml) 15 0 535
Iron (μg/dl) 45–160 15
Iron-binding capacity (μg/dl) 23 4 181
Ferritin (μg/liter) 2 00 864
Transferrin saturation (%) 14–50 8
Reticulocyte count (%) 0.5–2.5 <0.5
Haptoglobin (mg/dl) 16–199 214
Lactic acid (mmol/liter)   3.7
Venous blood gas measurements
pH 7.31
Partial pressure of carbon dioxide 50
Partial pressure of oxygen 28
Urine
Color Yellow Yellow Yellow Dark yellow Yellow Yellow
Clarity Clear Clear Clear Clear Clear Clear
Specific gravity 1.033 1.030   1.016 1.032 1.016
pH 7.0 6.0   5.0 5.0 5.0
Protein 1+ Negative 2+ 1+ Negative
White cells per high-power field    
Red cells per high-power field    ",Perforation of the sigmoid colon by a foreign body (toothpick) that caused a fistula to the right common iliac artery.,"Perforation of the sigmoid colon by a foreign body, with an adjacent abscess and a possible arterioenteric fistula involving the right common iliac artery with resulting intestinal bleeding.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 18-year-old male professional athlete was admitted to this hospital because of fevers, abdominal pain, and hematochezia.
The patient had been well until 20 days before this admission, when fevers and pain in the right lower quadrant developed during a trip to the southeastern United States for athletic training. One day later, the patient had mild postprandial nausea and loose stools. He presented to a local emergency department for evaluation.
In the emergency department of the first hospital, the pulse was 59 beats per minute, the blood pressure 114/65 mm Hg, and the weight 72.1 kg. The results of the rest of the physical examination were not documented. The blood levels of electrolytes, calcium, alkaline phosphatase, total bilirubin, and lipase were normal; other laboratory test results are shown in Table 1. The results of computed tomography (CT) of the abdomen and pelvis, performed after the administration of oral and intravenous contrast material, were reportedly normal. After 5 hours of observation, the patient was discharged to his hotel without receiving a specific diagnosis.	
Table 1 
During the next 2 weeks, the abdominal pain diminished and the fevers and loose stools resolved; mild nausea persisted. The patient traveled with his team to the western United States and participated in reduced-intensity athletic training. Four days before this admission, pain in the right lower quadrant recurred and was associated with low-back pain on the right side. In addition, he produced well-formed stools that contained blood. The following day, the abdominal and back pain persisted. Because the patient had not had a bowel movement, his athletic trainer recommended that he take a rectal suppository. After he took the suppository, he had a bowel movement that consisted of loose stools admixed with blood and mucus. That evening, a temperature of 39.7[degrees]C developed, prompting the patient to present to the emergency department of a second hospital.
In the emergency department of the second hospital, the patient reported pain in the right flank and abdomen and loss of appetite. The temperature was 38.9[degrees]C, the pulse 110 beats per minute, the blood pressure 124/76 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. The lower quadrants of the abdomen and the right flank were tender; the remainder of the examination was normal. The anion gap and blood levels of electrolytes, calcium, alkaline phosphatase, total bilirubin, and lipase were normal; other laboratory test results are shown in Table 1. Magnetic resonance imaging (MRI) of the abdomen and pelvis, performed after the administration of intravenous contrast material, reportedly revealed mildly distended, fluid-filled loops of small bowel in the left half of the abdomen and the presence of air-fluid levels in the rectum. Acetaminophen and intravenous fluids were administered, and the fever and tachycardia resolved. The team's internist encouraged the patient to return to New England for further medical evaluation.
Two days later and 1 day before this admission, the patient was seen by the team's internist at an outpatient clinic of this hospital. He reported that the abdominal and back pain persisted. He also reported that, earlier that day, he had had a temperature of 38.9[degrees]C, which had decreased after the administration of acetaminophen, and produced well-formed stools that contained blood. The patient appeared to be uncomfortable. The temperature was 36.3[degrees]C, the pulse 84 beats per minute, and the blood pressure 110/74 mm Hg. The abdomen was soft, with normal bowel sounds; there was tenderness in the right lower quadrant and the suprapubic region, without guarding, rebound tenderness, or masses. The remainder of the examination was normal. Arrangements were made for an expedited colonoscopy to be performed by a gastroenterologist at this hospital the following afternoon.
The next morning, the patient called the team's internist and reported that, after he had taken the bowel-preparation regimen, he had had a bowel movement that contained a large volume of blood. He also reported shaking chills and fever, with temperatures as high as 39.4[degrees]C, as well as worsening pain in the right lower quadrant. He was advised to present to the emergency department of this hospital.
In the emergency department of this hospital, the patient reported light-headedness and malaise. His medications included ibuprofen and acetaminophen as needed, and he had no known allergies. A review of systems was negative for emesis, diarrhea, tenesmus, genitourinary symptoms, arthralgias, rash, and skin and oral ulcerations. The patient was a professional athlete who lived with his family in an urban area of New England and traveled frequently throughout the continental United States. He did not smoke tobacco, drink alcohol, or use illicit drugs. There was no family history of autoimmune diseases or inflammatory bowel disease.
The patient appeared to be tired. The temperature was 37.6[degrees]C, the pulse 122 beats per minute, the blood pressure 110/56 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. The weight was 72.3 kg, the height 185 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.1. The abdomen was soft, with normal bowel sounds; there was tenderness on palpation of the right lower quadrant and the suprapubic region, without guarding, rigidity, distention, or masses. Examination of the rectum revealed a few external hemorrhoids, and there was scant bright-red blood in the rectal vault; there were no skin tags or palpable fissures or masses. There was no testicular tenderness, warmth, or erythema, but there was an enlarged right inguinal lymph node. The remainder of the examination was normal.
Blood samples were obtained for culture. Stool samples, which were liquid and bloody, were obtained for culture, examination for ova and parasites, tests for antigens of Clostridium difficile and Shiga toxins 1 and 2, and measurement of the calprotectin level. The anion gap and blood levels of electrolytes, calcium, magnesium, alkaline phosphatase, total bilirubin, direct bilirubin, and lipase were normal; other laboratory test results are shown in Table 1. Tests for infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and Helicobacter pylori were negative. Intravenous fluids were administered, and CT of the abdomen and pelvis was performed. On the initial interpretation of the CT scan, no evidence of an acute process in the abdomen or pelvis was detected and the appendix was not visible.
The patient was admitted to the hospital. That evening, a temperature of 40.2[degrees]C developed, with associated rigors, and the patient appeared to be confused. The pulse was 145 beats per minute, the blood pressure 109/52 mm Hg, the respiratory rate 35 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. There was a new systolic ejection murmur (grade 2/6) that was best heard at the left upper sternal border; the remainder of the examination was unchanged. Another blood sample was obtained for culture. The lactate dehydrogenase level was normal; other laboratory test results are shown in Table 1. Cefepime, metronidazole, acetaminophen, and intravenous fluids were administered, and the vital signs and mental status normalized. Ninety minutes after the initiation of treatment, the microbiology laboratory reported that cultures of the blood that had been obtained in the emergency department 11.5 hours earlier had grown gram-negative rods.
During the next day, additional fevers occurred, with temperatures as high as 40.6[degrees]C and with associated rigors. Cultures of the blood that had been obtained in the emergency department grew Klebsiella pneumoniae and gram-positive cocci, and repeat blood cultures reportedly grew a second type of gram-negative rod.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 18-year-old male professional athlete was admitted to this hospital because of fevers, abdominal pain, and hematochezia.
The patient had been well until 20 days before this admission, when fevers and pain in the right lower quadrant developed during a trip to the southeastern United States for athletic training. One day later, the patient had mild postprandial nausea and loose stools. He presented to a local emergency department for evaluation.
In the emergency department of the first hospital, the pulse was 59 beats per minute, the blood pressure 114/65 mm Hg, and the weight 72.1 kg. The results of the rest of the physical examination were not documented. The blood levels of electrolytes, calcium, alkaline phosphatase, total bilirubin, and lipase were normal; other laboratory test results are shown in Table 1. The results of computed tomography (CT) of the abdomen and pelvis, performed after the administration of oral and intravenous contrast material, were reportedly normal. After 5 hours of observation, the patient was discharged to his hotel without receiving a specific diagnosis.	
Table 1 
During the next 2 weeks, the abdominal pain diminished and the fevers and loose stools resolved; mild nausea persisted. The patient traveled with his team to the western United States and participated in reduced-intensity athletic training. Four days before this admission, pain in the right lower quadrant recurred and was associated with low-back pain on the right side. In addition, he produced well-formed stools that contained blood. The following day, the abdominal and back pain persisted. Because the patient had not had a bowel movement, his athletic trainer recommended that he take a rectal suppository. After he took the suppository, he had a bowel movement that consisted of loose stools admixed with blood and mucus. That evening, a temperature of 39.7[degrees]C developed, prompting the patient to present to the emergency department of a second hospital.
In the emergency department of the second hospital, the patient reported pain in the right flank and abdomen and loss of appetite. The temperature was 38.9[degrees]C, the pulse 110 beats per minute, the blood pressure 124/76 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. The lower quadrants of the abdomen and the right flank were tender; the remainder of the examination was normal. The anion gap and blood levels of electrolytes, calcium, alkaline phosphatase, total bilirubin, and lipase were normal; other laboratory test results are shown in Table 1. Magnetic resonance imaging (MRI) of the abdomen and pelvis, performed after the administration of intravenous contrast material, reportedly revealed mildly distended, fluid-filled loops of small bowel in the left half of the abdomen and the presence of air-fluid levels in the rectum. Acetaminophen and intravenous fluids were administered, and the fever and tachycardia resolved. The team's internist encouraged the patient to return to New England for further medical evaluation.
Two days later and 1 day before this admission, the patient was seen by the team's internist at an outpatient clinic of this hospital. He reported that the abdominal and back pain persisted. He also reported that, earlier that day, he had had a temperature of 38.9[degrees]C, which had decreased after the administration of acetaminophen, and produced well-formed stools that contained blood. The patient appeared to be uncomfortable. The temperature was 36.3[degrees]C, the pulse 84 beats per minute, and the blood pressure 110/74 mm Hg. The abdomen was soft, with normal bowel sounds; there was tenderness in the right lower quadrant and the suprapubic region, without guarding, rebound tenderness, or masses. The remainder of the examination was normal. Arrangements were made for an expedited colonoscopy to be performed by a gastroenterologist at this hospital the following afternoon.
The next morning, the patient called the team's internist and reported that, after he had taken the bowel-preparation regimen, he had had a bowel movement that contained a large volume of blood. He also reported shaking chills and fever, with temperatures as high as 39.4[degrees]C, as well as worsening pain in the right lower quadrant. He was advised to present to the emergency department of this hospital.
In the emergency department of this hospital, the patient reported light-headedness and malaise. His medications included ibuprofen and acetaminophen as needed, and he had no known allergies. A review of systems was negative for emesis, diarrhea, tenesmus, genitourinary symptoms, arthralgias, rash, and skin and oral ulcerations. The patient was a professional athlete who lived with his family in an urban area of New England and traveled frequently throughout the continental United States. He did not smoke tobacco, drink alcohol, or use illicit drugs. There was no family history of autoimmune diseases or inflammatory bowel disease.
The patient appeared to be tired. The temperature was 37.6[degrees]C, the pulse 122 beats per minute, the blood pressure 110/56 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. The weight was 72.3 kg, the height 185 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.1. The abdomen was soft, with normal bowel sounds; there was tenderness on palpation of the right lower quadrant and the suprapubic region, without guarding, rigidity, distention, or masses. Examination of the rectum revealed a few external hemorrhoids, and there was scant bright-red blood in the rectal vault; there were no skin tags or palpable fissures or masses. There was no testicular tenderness, warmth, or erythema, but there was an enlarged right inguinal lymph node. The remainder of the examination was normal.
Blood samples were obtained for culture. Stool samples, which were liquid and bloody, were obtained for culture, examination for ova and parasites, tests for antigens of Clostridium difficile and Shiga toxins 1 and 2, and measurement of the calprotectin level. The anion gap and blood levels of electrolytes, calcium, magnesium, alkaline phosphatase, total bilirubin, direct bilirubin, and lipase were normal; other laboratory test results are shown in Table 1. Tests for infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and Helicobacter pylori were negative. Intravenous fluids were administered, and CT of the abdomen and pelvis was performed. On the initial interpretation of the CT scan, no evidence of an acute process in the abdomen or pelvis was detected and the appendix was not visible.
The patient was admitted to the hospital. That evening, a temperature of 40.2[degrees]C developed, with associated rigors, and the patient appeared to be confused. The pulse was 145 beats per minute, the blood pressure 109/52 mm Hg, the respiratory rate 35 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. There was a new systolic ejection murmur (grade 2/6) that was best heard at the left upper sternal border; the remainder of the examination was unchanged. Another blood sample was obtained for culture. The lactate dehydrogenase level was normal; other laboratory test results are shown in Table 1. Cefepime, metronidazole, acetaminophen, and intravenous fluids were administered, and the vital signs and mental status normalized. Ninety minutes after the initiation of treatment, the microbiology laboratory reported that cultures of the blood that had been obtained in the emergency department 11.5 hours earlier had grown gram-negative rods.
During the next day, additional fevers occurred, with temperatures as high as 40.6[degrees]C and with associated rigors. Cultures of the blood that had been obtained in the emergency department grew Klebsiella pneumoniae and gram-positive cocci, and repeat blood cultures reportedly grew a second type of gram-negative rod.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fever, abdominal pain, and hematochezia, along with the presence of Klebsiella pneumoniae and gram-positive cocci in his blood cultures, suggest a severe bacterial infection. The patient's history of travel to the southeastern United States, his professional athlete status, and his symptoms of right lower quadrant and low-back pain, nausea, and bloody stools are suggestive of an intestinal infection. The presence of an enlarged right inguinal lymph node also suggests a localized infection. The fact that the patient's symptoms initially improved but then worsened again, along with the presence of multiple types of bacteria in his blood, suggests a complicated infection that may have spread from the initial site. The presence of blood in the patient's stools suggests that the infection may have caused damage to the intestinal lining, leading to bleeding. The patient's high fever and confusion suggest that the infection may have spread to his bloodstream, causing sepsis. \n\nDiagnosis: Sepsis due to complicated intestinal infection.""
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        ""content"": ""The patient is an 18-year-old male with a history of recent travel to the southeastern United States who presents with fever, abdominal pain, and hematochezia. The differential diagnosis for this patient includes infectious causes such as bacterial gastroenteritis, viral gastroenteritis, or parasitic infection; inflammatory bowel disease such as Crohn's disease or ulcerative colitis; and ischemic colitis. The patient's recent travel history raises the possibility of a travel-related infection. However, the patient's symptoms have been ongoing for 20 days, which is a relatively long duration for a typical case of gastroenteritis. The patient's abdominal pain and hematochezia could be consistent with inflammatory bowel disease, but he does not have a family history of this condition. Ischemic colitis is unlikely given the patient's young age and lack of risk factors. The patient's blood cultures grew Klebsiella pneumoniae and gram-positive cocci, indicating a bacterial infection. The presence of two types of bacteria suggests a polymicrobial infection, which is more common in intra-abdominal infections. The patient's symptoms and the results of his blood cultures suggest an intra-abdominal infection such as appendicitis or diverticulitis. However, the patient's CT scan did not show evidence of an acute process in the abdomen or pelvis, and the appendix was not visible. This makes appendicitis or diverticulitis less likely. The patient's symptoms, the results of his blood cultures, and the lack of findings on his CT scan suggest a diagnosis of infectious colitis.\n\nDiagnosis: Infectious colitis.""
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10.1056/NEJMcpc1815528,"Case 3-2019: A 70-Year-Old Woman with Fever, Headache, and Progressive Encephalopathy","Hemoglobin (g/dl)  11.6 10.8   12.6
Hematocrit (%)  34.7 32.5   36.6
White-cell count (per mm3)  8600 8200   9300
Differential count (%)
Neutrophils 47–80 88
Immature granulocytes <1 1
Lymphocytes 14–46 7
Monocytes  5
Eosinophils  0
Basophils   0
Glucose (mg/dl) 70–99 114 115   116
Cerebrospinal fluid
Color Colorless Colorless
Turbidity Clear Slight
Xanthochromia None None
Red-cell count (per mm3) 579 0–5 17
Total nucleated-cell count (per mm3
) 9 0–5 73
Differential count (%)
Neutrophils 11 0 1
Lymphocytes 76  89
Monocytes 13  10
Protein (g/dl) 61  117
Glucose (mg/dl) 63 52
Gram’s stain 1+ Polymorphonu‑
clear leukocytes,
no organisms
A few mononuclear 
cells, no organisms",Powassan virus encephalitis.,Powassan virus meningoencephalitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old woman with a history of migraines was admitted to this hospital in the fall because of fever, headache, and progressive encephalopathy.
The patient had been in her usual state of health until 12 days before this admission, when fevers with temperatures as high as 39.7[degrees]C developed, along with chills, fatigue, weakness, and headache. The patient also had nausea and intermittent episodes of vomiting. She took acetaminophen and sumatriptan, but the symptoms persisted. On the sixth day of illness, she was seen by her primary care physician. A rapid influenza test was negative, and the results of urinalysis were reportedly normal; a blood sample was sent to the laboratory for testing for Borrelia burgdorferi antibodies.
The following day, the patient was seen in the emergency department at another hospital for further evaluation. On examination, she was febrile and appeared ill. The platelet count, prothrombin-time international normalized ratio, anion gap, and blood levels of electrolytes and lactate were normal, as were the results of renal-function tests and urinalysis; other laboratory test results are shown in Table 1. Blood and urine specimens were sent for culture. A chest radiograph was normal. A lumbar puncture was performed; the results of cerebrospinal fluid (CSF) analysis are shown in Table 1. Vancomycin and piperacillin-tazobactam were administered intravenously, and admission to the hospital was recommended. The patient declined admission and was discharged home with a prescription for oral doxycycline.	
Table 1 
During the next 2 days, fevers persisted, and the patient became progressively less interactive. She got out of bed infrequently; she had an unsteady gait and needed assistance to walk. Oral intake decreased, frequency of urination increased, and tremulousness of the arms and jaw developed. On the ninth day of illness (4 days before this admission), the patient's family again took her to the emergency department at the other hospital. On examination, the patient appeared uncomfortable and ill and was trembling. She was alert and oriented, followed commands, and responded to questions with single-word answers. The temperature was 39.4[degrees]C; the other vital signs were normal. The oral mucous membranes appeared dry. The platelet count, anion gap, venous blood gas measurements, and blood levels of electrolytes, lactate, and ammonia were normal, as were the results of renal-function tests, liver-function tests, and urinalysis; other laboratory test results are shown in Table 1. The test for B. burgdorferi antibodies (for which a sample had been sent 3 days earlier) was negative, as were the blood and urine cultures (for which samples had been sent 2 days earlier). Blood specimens were obtained, and imaging studies were performed.
Results of computed tomography (CT) of the head, performed after the intravenous administration of contrast material, were normal. CT of the abdomen and pelvis, performed after the intravenous administration of contrast material, revealed trace bilateral pleural effusions, four indeterminate lesions (8 to 20 mm in diameter) in the liver, a nonobstructive calculus (2 mm in diameter) in the lower pole of the left kidney, subcentimeter hypodensities in both kidneys, trace free fluid in the pelvis, diffuse atherosclerotic calcifications in the aorta and its visualized branches, colonic diverticula, and degenerative changes of the bony skeleton.
A bolus of normal saline was administered intravenously, and the patient was admitted to the other hospital. Acyclovir, ceftriaxone, vancomycin, ampicillin, acetaminophen, and intravenous fluids were administered. During the next 3 days, intermittent fevers with temperatures as high as 38.4[degrees]C continued, and the patient became disoriented and then mute. She was no longer able to follow commands. Urinary retention, lead-pipe muscular rigidity in the arms and legs, increased deep-tendon reflexes, and nuchal rigidity with passive flexion developed. Polymerase-chain-reaction (PCR) assays for herpes simplex virus DNA and enterovirus RNA, performed on the CSF sample obtained during the first emergency department visit, were negative. The erythrocyte sedimentation rate and blood levels of C3, C4, thyrotropin, folate, and vitamin B12 were normal, and blood tests for human immunodeficiency virus antibodies, Treponema pallidum antibodies, cryptococcal antigen, Anaplasma phagocytophilum DNA, babesia species DNA, antinuclear antibodies, and [beta]2-glycoprotein antibodies were negative. An electrocardiogram and transthoracic echocardiogram were normal. Magnetic resonance imaging (MRI) of the head, performed after the intravenous administration of contrast material, reportedly revealed diffuse abnormal meningeal enhancement that was most notable in the cerebellum. Acyclovir was discontinued.
On the fourth hospital day, the patient had a 2-minute episode during which the eyes rolled upward and the arms and legs stiffened. Lorazepam and levetiracetam were administered. Electroencephalography that was performed after the event revealed generalized slowing. The patient was transferred to this hospital for further treatment.
On admission, additional history was obtained from the patient's family. The patient had had mild cognitive decline during the past year, and her son had begun assisting with management of her finances. Approximately 3 weeks before the onset of illness, the patient had noticed a dime-sized erythematous lesion on the right shoulder and thought it might have resulted from an insect bite. During the week before the onset of illness, she had been seen by a dentist for an unspecified treatment and had taken clindamycin for 2 days. She had a history of migraines, fibromyalgia, depression, and anxiety, and in the remote past she had undergone cholecystectomy, hysterectomy, and treatment for Lyme disease. Her medications included citalopram and sumatriptan; she had no known allergies. She lived with her husband, two adult children, and pet dogs and cats near a horse farm in a wooded area of northern New England. She enjoyed spending time outdoors and frequently removed ticks from her pets. She did not smoke tobacco or use illicit drugs, and she drank alcohol rarely. There was a family history of Alzheimer's disease and stroke.
On examination, the vital signs were normal. The patient was somnolent, nonverbal, and unable to follow commands. She intermittently opened her eyes in response to a loud voice and tracked the examiner with conjugate gaze. There was no movement of the arms after application of pressure to the beds of the fingernails; triple flexion occurred after application of pressure to the beds of the toenails. Deep-tendon reflexes in the arms and legs were brisk. Nuchal rigidity was present. There was a systolic ejection murmur (grade 2/6) at the left sternal border. The remainder of the general physical examination was normal. The red-cell indexes, platelet count, prothrombin time, partial-thromboplastin time, anion gap, and blood levels of electrolytes were normal, as were the results of renal-function and liver-function tests; other laboratory test results are shown in Table 1. A lumbar puncture was performed, with an opening pressure of 18 cm of water; the results of CSF analysis are shown in Table 1.
Dr. R. Gilberto Gonzalez: MRI of the head (Figure 1) revealed findings consistent with progressive meningoencephalitis. The findings were most prominent in the cerebellar hemispheres and were more severe on the left side than on the right side. There was associated edema in the cerebellar hemispheres. As compared with the previous MRI study, this study showed an increase in effacement involving the fourth ventricle and an increase in the size of the lateral and third ventricles, findings suggestive of early obstructive hydrocephalus. Results of magnetic resonance angiography of the head and neck were normal.	
Figure 1 
Dr. Hogan: A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 70-year-old woman with a history of migraines was admitted to this hospital in the fall because of fever, headache, and progressive encephalopathy.
The patient had been in her usual state of health until 12 days before this admission, when fevers with temperatures as high as 39.7[degrees]C developed, along with chills, fatigue, weakness, and headache. The patient also had nausea and intermittent episodes of vomiting. She took acetaminophen and sumatriptan, but the symptoms persisted. On the sixth day of illness, she was seen by her primary care physician. A rapid influenza test was negative, and the results of urinalysis were reportedly normal; a blood sample was sent to the laboratory for testing for Borrelia burgdorferi antibodies.
The following day, the patient was seen in the emergency department at another hospital for further evaluation. On examination, she was febrile and appeared ill. The platelet count, prothrombin-time international normalized ratio, anion gap, and blood levels of electrolytes and lactate were normal, as were the results of renal-function tests and urinalysis; other laboratory test results are shown in Table 1. Blood and urine specimens were sent for culture. A chest radiograph was normal. A lumbar puncture was performed; the results of cerebrospinal fluid (CSF) analysis are shown in Table 1. Vancomycin and piperacillin-tazobactam were administered intravenously, and admission to the hospital was recommended. The patient declined admission and was discharged home with a prescription for oral doxycycline.	
Table 1 
During the next 2 days, fevers persisted, and the patient became progressively less interactive. She got out of bed infrequently; she had an unsteady gait and needed assistance to walk. Oral intake decreased, frequency of urination increased, and tremulousness of the arms and jaw developed. On the ninth day of illness (4 days before this admission), the patient's family again took her to the emergency department at the other hospital. On examination, the patient appeared uncomfortable and ill and was trembling. She was alert and oriented, followed commands, and responded to questions with single-word answers. The temperature was 39.4[degrees]C; the other vital signs were normal. The oral mucous membranes appeared dry. The platelet count, anion gap, venous blood gas measurements, and blood levels of electrolytes, lactate, and ammonia were normal, as were the results of renal-function tests, liver-function tests, and urinalysis; other laboratory test results are shown in Table 1. The test for B. burgdorferi antibodies (for which a sample had been sent 3 days earlier) was negative, as were the blood and urine cultures (for which samples had been sent 2 days earlier). Blood specimens were obtained, and imaging studies were performed.
Results of computed tomography (CT) of the head, performed after the intravenous administration of contrast material, were normal. CT of the abdomen and pelvis, performed after the intravenous administration of contrast material, revealed trace bilateral pleural effusions, four indeterminate lesions (8 to 20 mm in diameter) in the liver, a nonobstructive calculus (2 mm in diameter) in the lower pole of the left kidney, subcentimeter hypodensities in both kidneys, trace free fluid in the pelvis, diffuse atherosclerotic calcifications in the aorta and its visualized branches, colonic diverticula, and degenerative changes of the bony skeleton.
A bolus of normal saline was administered intravenously, and the patient was admitted to the other hospital. Acyclovir, ceftriaxone, vancomycin, ampicillin, acetaminophen, and intravenous fluids were administered. During the next 3 days, intermittent fevers with temperatures as high as 38.4[degrees]C continued, and the patient became disoriented and then mute. She was no longer able to follow commands. Urinary retention, lead-pipe muscular rigidity in the arms and legs, increased deep-tendon reflexes, and nuchal rigidity with passive flexion developed. Polymerase-chain-reaction (PCR) assays for herpes simplex virus DNA and enterovirus RNA, performed on the CSF sample obtained during the first emergency department visit, were negative. The erythrocyte sedimentation rate and blood levels of C3, C4, thyrotropin, folate, and vitamin B12 were normal, and blood tests for human immunodeficiency virus antibodies, Treponema pallidum antibodies, cryptococcal antigen, Anaplasma phagocytophilum DNA, babesia species DNA, antinuclear antibodies, and [beta]2-glycoprotein antibodies were negative. An electrocardiogram and transthoracic echocardiogram were normal. Magnetic resonance imaging (MRI) of the head, performed after the intravenous administration of contrast material, reportedly revealed diffuse abnormal meningeal enhancement that was most notable in the cerebellum. Acyclovir was discontinued.
On the fourth hospital day, the patient had a 2-minute episode during which the eyes rolled upward and the arms and legs stiffened. Lorazepam and levetiracetam were administered. Electroencephalography that was performed after the event revealed generalized slowing. The patient was transferred to this hospital for further treatment.
On admission, additional history was obtained from the patient's family. The patient had had mild cognitive decline during the past year, and her son had begun assisting with management of her finances. Approximately 3 weeks before the onset of illness, the patient had noticed a dime-sized erythematous lesion on the right shoulder and thought it might have resulted from an insect bite. During the week before the onset of illness, she had been seen by a dentist for an unspecified treatment and had taken clindamycin for 2 days. She had a history of migraines, fibromyalgia, depression, and anxiety, and in the remote past she had undergone cholecystectomy, hysterectomy, and treatment for Lyme disease. Her medications included citalopram and sumatriptan; she had no known allergies. She lived with her husband, two adult children, and pet dogs and cats near a horse farm in a wooded area of northern New England. She enjoyed spending time outdoors and frequently removed ticks from her pets. She did not smoke tobacco or use illicit drugs, and she drank alcohol rarely. There was a family history of Alzheimer's disease and stroke.
On examination, the vital signs were normal. The patient was somnolent, nonverbal, and unable to follow commands. She intermittently opened her eyes in response to a loud voice and tracked the examiner with conjugate gaze. There was no movement of the arms after application of pressure to the beds of the fingernails; triple flexion occurred after application of pressure to the beds of the toenails. Deep-tendon reflexes in the arms and legs were brisk. Nuchal rigidity was present. There was a systolic ejection murmur (grade 2/6) at the left sternal border. The remainder of the general physical examination was normal. The red-cell indexes, platelet count, prothrombin time, partial-thromboplastin time, anion gap, and blood levels of electrolytes were normal, as were the results of renal-function and liver-function tests; other laboratory test results are shown in Table 1. A lumbar puncture was performed, with an opening pressure of 18 cm of water; the results of CSF analysis are shown in Table 1.
Dr. R. Gilberto Gonzalez: MRI of the head (Figure 1) revealed findings consistent with progressive meningoencephalitis. The findings were most prominent in the cerebellar hemispheres and were more severe on the left side than on the right side. There was associated edema in the cerebellar hemispheres. As compared with the previous MRI study, this study showed an increase in effacement involving the fourth ventricle and an increase in the size of the lateral and third ventricles, findings suggestive of early obstructive hydrocephalus. Results of magnetic resonance angiography of the head and neck were normal.	
Figure 1 
Dr. Hogan: A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fever, headache, and progressive encephalopathy, along with her history of spending time outdoors and frequently removing ticks from her pets, suggest a tick-borne illness. The patient's location in northern New England and her history of a recent erythematous lesion on her shoulder further support this. The negative tests for Borrelia burgdorferi, Anaplasma phagocytophilum, and babesia species rule out Lyme disease, anaplasmosis, and babesiosis, respectively. The cerebrospinal fluid analysis showing lymphocytic pleocytosis and elevated protein is consistent with a central nervous system infection. The MRI findings of progressive meningoencephalitis, particularly in the cerebellar hemispheres, are consistent with Powassan virus, a tick-borne flavivirus that can cause severe neurologic disease. \n\nDiagnosis: Powassan virus encephalitis.""
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10.1056/NEJMcpc1810390,"Case 2-2019: A 36-Year-Old Man with Rash, Abdominal Pain, and Lymphadenopathy","Hematocrit (%)   39.9 30.2
Hemoglobin (g/dl)   13.0 9.3
White-cell count (per mm3)   7370 9460
Differential count (%)
Neutrophils   63.1 75.8
Lymphocytes   24.4 11.2
Monocytes   11.5 11.7
Eosinophils   0.8 0.5
Basophils   0.1 0.2
Platelet count (per mm3
)   167,000 301,000
Red-cell count (per mm3
)   6,760,000 5,510,000
Mean corpuscular volume (fl)   59.0 54.8
Mean corpuscular hemoglobin (pg) 26. 4.0 19.2 16.9
Mean corpuscular hemoglobin concentration (g/dl) 31. 7.0 32.6 30.8
Total protein (g/dl) 6. .3 8.2 8.6
Albumin (g/dl)   4.9 3.3
d-dimer (ng/ml)   734",Papulonecrotic tuberculid (cutaneous tuberculosis).,Papulonecrotic tuberculid (cutaneous tuberculosis).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 36-year-old man was admitted to this hospital because of abdominal pain, rash, and lymphadenopathy.
The patient had been well until 4 years before admission, when swelling developed in the right side of the neck. One year later, he was evaluated at this hospital and reported that the neck swelling had persisted but had not changed in size. He also reported that he had had no fevers, night sweats, or weight loss. On examination, there was an enlarged posterior cervical lymph node (2 cm in diameter) on the right side. The node was mildly tender and freely mobile, with a rubbery texture and slightly irregular shape. Results of liver-function tests were normal, as were blood levels of iron, ferritin, and total iron-binding capacity. A test for heterophile antibodies and a fourth-generation combination assay for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) antibodies and HIV-1 p24 antigen were negative; other laboratory test results are shown in Table 1. Chest radiography revealed a normal cardiac silhouette and clear lungs. Biopsy of the lymph node was recommended, but the patient elected not to undergo the procedure.	
Table 1 
Two years before admission, a diffuse, painless, erythematous, papular rash developed on the trunk and then spread to the arms, legs, scalp, and face. The papules appeared in separate crops, and over a period of 1 to 2 months, a small amount of purulent material drained from each papule, after which the lesions evolved into hyperpigmented nodules. The rash persisted, and 6 months later, the patient was evaluated at another hospital. A biopsy of the skin of the left arm was performed, and histopathological examination of the biopsy specimen revealed findings consistent with acute folliculitis. Treatment with doxycycline was initiated, but the rash persisted, with a waxing and waning pattern, during the next 8 months. Doxycycline was discontinued. Subsequent treatment with topical clobetasol resulted in only a mild decrease in the rash.
Six weeks before admission, a biopsy of the skin of the right thigh was performed. Histopathological examination of the biopsy specimen revealed acute neutrophilic folliculitis, with follicular rupture in the middle dermis and associated acute and chronic inflammation. Surface bacteria and yeast were present, but there were no bacterial or fungal organisms in the dermis. Treatment with oral clindamycin and rifampin was begun, and the patient was instructed to wash twice daily with chlorhexidine and apply mupirocin to open papules.
One day before admission, abdominal pain developed in the right upper quadrant. The pain was sharp, constant, worsened by movement and deep breathing, and unchanged with eating. There was no nausea, vomiting, or diarrhea. The pain progressively worsened during the next 24 hours, and the patient presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported ongoing abdominal pain, as well as weight loss of 4.5 kg during the past year, which he attributed to increased regular exercise at a gym. Four weeks before admission, he had stopped exercising because of increased fatigue with exertion. The patient reported that he had not had fevers but had occasionally changed his pajamas at night because of sweating. He had microcytic anemia that had been attributed to [beta]-thalassemia minor. The only medications were clindamycin and rifampin, and there were no known drug allergies.
The patient was born in Morocco and had moved to the United States 10 years before admission. He visited his family in a rural village in Morocco every few years, with the last visit occurring 5 months earlier. He had never smoked tobacco, and he did not drink alcohol or use illicit drugs. He did not consume unpasteurized dairy products. His father had died of complications of emphysema.
On examination, the temperature was 37.6[degrees]C, the pulse 66 beats per minute, the blood pressure 132/82 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 76.2 kg; the last recorded weight, which had been obtained 4 years earlier, was 81.8 kg. The patient did not appear to be ill but was in mild distress because of abdominal pain. Erythematous, follicular papules and hyperpigmented nodules, some with central erosion and ulceration, were distributed on the trunk, arms, legs, face, and scalp (Figure 1). Examination of the heart and lungs was normal. Bowel sounds were present, and the abdomen was soft, with tenderness on palpation of the right upper quadrant, but was not distended. There was right axillary lymphadenopathy but no submandibular, cervical, supraclavicular, or inguinal lymphadenopathy. Blood levels of electrolytes, glucose, and lactate dehydrogenase were normal, as were results of renal-function and liver-function tests; other laboratory test results are shown in Table 1. Tests for antibodies to hepatitis B virus (HBV) surface antigen and antibodies to HBV core antigen were positive. Tests for HBV surface antigen, hepatitis C virus antibodies, and Treponema pallidum antibodies were negative, as was a fourth-generation combination assay for HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen. Urinalysis revealed normal findings, and blood cultures were negative. Imaging studies were obtained.	
Figure 1
Dr. Alexis M. Cahalane: Abdominal ultrasonography revealed an ill-defined mass (9.0 cm by 5.6 cm) in the right lobe of the liver, with no evidence of dilatation of intrahepatic bile ducts. Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material (Figure 2A and 2B), revealed multiple prominent cardiophrenic lymph nodes (<=1 cm in maximal short-axis diameter) predominantly on the right side. There were also multiple enlarged axillary lymph nodes (<=3.4 cm in maximal short-axis diameter) on the right side, including some with central necrosis. CT of the abdomen and pelvis (Figure 2C) revealed multiple ill-defined hypodensities throughout the right lobe and in the fourth segment of the liver, with the largest measuring 2.7 cm by 2.0 cm. Trace perihepatic ascites and mild splenomegaly were present, with the spleen measuring 13.5 cm in craniocaudal dimension.	
Figure 2
Magnetic resonance imaging (MRI) of the liver, performed after the administration of intravenous contrast material (Figure 2D, 2E, and 2F), revealed multiple areas of abnormality in the right lobe that corresponded to the lesions seen on CT, with the largest measuring 3.1 cm by 6.3 cm by 3.5 cm. The lesions had mild peripheral hyperintensity on T2-weighted images and restricted diffusion on diffusion-weighted images. On images obtained during the portal venous phase, the lesions had peripheral enhancement with central hypoenhancement. On images obtained 4 minutes after the administration of contrast material, the lesions had a ""cluster of grapes"" appearance. Mild splenomegaly was also detected.
Dr. Schiavoni: The patient was admitted to the hospital, and fine-needle aspiration and core biopsy of a right axillary lymph node were performed.
Dr. Ruth K. Foreman: Examination of the aspirate and biopsy specimen (Figure 3) revealed benign-appearing lymph-node tissue with normal architecture and associated necroinflammatory debris. There was no histologic evidence of cancer. Acid-fast, Gomori methenamine-silver, periodic acid-Schiff, Brown-Hopps, and Steiner stains for microorganisms were negative, as was an immunohistochemical stain for spirochetes. Tissue from the biopsy was sent to the microbiology laboratory for culture.	
Figure 3 
Dr. Schiavoni: Additional diagnostic tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 36-year-old man was admitted to this hospital because of abdominal pain, rash, and lymphadenopathy.
The patient had been well until 4 years before admission, when swelling developed in the right side of the neck. One year later, he was evaluated at this hospital and reported that the neck swelling had persisted but had not changed in size. He also reported that he had had no fevers, night sweats, or weight loss. On examination, there was an enlarged posterior cervical lymph node (2 cm in diameter) on the right side. The node was mildly tender and freely mobile, with a rubbery texture and slightly irregular shape. Results of liver-function tests were normal, as were blood levels of iron, ferritin, and total iron-binding capacity. A test for heterophile antibodies and a fourth-generation combination assay for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) antibodies and HIV-1 p24 antigen were negative; other laboratory test results are shown in Table 1. Chest radiography revealed a normal cardiac silhouette and clear lungs. Biopsy of the lymph node was recommended, but the patient elected not to undergo the procedure.	
Table 1 
Two years before admission, a diffuse, painless, erythematous, papular rash developed on the trunk and then spread to the arms, legs, scalp, and face. The papules appeared in separate crops, and over a period of 1 to 2 months, a small amount of purulent material drained from each papule, after which the lesions evolved into hyperpigmented nodules. The rash persisted, and 6 months later, the patient was evaluated at another hospital. A biopsy of the skin of the left arm was performed, and histopathological examination of the biopsy specimen revealed findings consistent with acute folliculitis. Treatment with doxycycline was initiated, but the rash persisted, with a waxing and waning pattern, during the next 8 months. Doxycycline was discontinued. Subsequent treatment with topical clobetasol resulted in only a mild decrease in the rash.
Six weeks before admission, a biopsy of the skin of the right thigh was performed. Histopathological examination of the biopsy specimen revealed acute neutrophilic folliculitis, with follicular rupture in the middle dermis and associated acute and chronic inflammation. Surface bacteria and yeast were present, but there were no bacterial or fungal organisms in the dermis. Treatment with oral clindamycin and rifampin was begun, and the patient was instructed to wash twice daily with chlorhexidine and apply mupirocin to open papules.
One day before admission, abdominal pain developed in the right upper quadrant. The pain was sharp, constant, worsened by movement and deep breathing, and unchanged with eating. There was no nausea, vomiting, or diarrhea. The pain progressively worsened during the next 24 hours, and the patient presented to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported ongoing abdominal pain, as well as weight loss of 4.5 kg during the past year, which he attributed to increased regular exercise at a gym. Four weeks before admission, he had stopped exercising because of increased fatigue with exertion. The patient reported that he had not had fevers but had occasionally changed his pajamas at night because of sweating. He had microcytic anemia that had been attributed to [beta]-thalassemia minor. The only medications were clindamycin and rifampin, and there were no known drug allergies.
The patient was born in Morocco and had moved to the United States 10 years before admission. He visited his family in a rural village in Morocco every few years, with the last visit occurring 5 months earlier. He had never smoked tobacco, and he did not drink alcohol or use illicit drugs. He did not consume unpasteurized dairy products. His father had died of complications of emphysema.
On examination, the temperature was 37.6[degrees]C, the pulse 66 beats per minute, the blood pressure 132/82 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 76.2 kg; the last recorded weight, which had been obtained 4 years earlier, was 81.8 kg. The patient did not appear to be ill but was in mild distress because of abdominal pain. Erythematous, follicular papules and hyperpigmented nodules, some with central erosion and ulceration, were distributed on the trunk, arms, legs, face, and scalp (Figure 1). Examination of the heart and lungs was normal. Bowel sounds were present, and the abdomen was soft, with tenderness on palpation of the right upper quadrant, but was not distended. There was right axillary lymphadenopathy but no submandibular, cervical, supraclavicular, or inguinal lymphadenopathy. Blood levels of electrolytes, glucose, and lactate dehydrogenase were normal, as were results of renal-function and liver-function tests; other laboratory test results are shown in Table 1. Tests for antibodies to hepatitis B virus (HBV) surface antigen and antibodies to HBV core antigen were positive. Tests for HBV surface antigen, hepatitis C virus antibodies, and Treponema pallidum antibodies were negative, as was a fourth-generation combination assay for HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen. Urinalysis revealed normal findings, and blood cultures were negative. Imaging studies were obtained.	
Figure 1
Dr. Alexis M. Cahalane: Abdominal ultrasonography revealed an ill-defined mass (9.0 cm by 5.6 cm) in the right lobe of the liver, with no evidence of dilatation of intrahepatic bile ducts. Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material (Figure 2A and 2B), revealed multiple prominent cardiophrenic lymph nodes (<=1 cm in maximal short-axis diameter) predominantly on the right side. There were also multiple enlarged axillary lymph nodes (<=3.4 cm in maximal short-axis diameter) on the right side, including some with central necrosis. CT of the abdomen and pelvis (Figure 2C) revealed multiple ill-defined hypodensities throughout the right lobe and in the fourth segment of the liver, with the largest measuring 2.7 cm by 2.0 cm. Trace perihepatic ascites and mild splenomegaly were present, with the spleen measuring 13.5 cm in craniocaudal dimension.	
Figure 2
Magnetic resonance imaging (MRI) of the liver, performed after the administration of intravenous contrast material (Figure 2D, 2E, and 2F), revealed multiple areas of abnormality in the right lobe that corresponded to the lesions seen on CT, with the largest measuring 3.1 cm by 6.3 cm by 3.5 cm. The lesions had mild peripheral hyperintensity on T2-weighted images and restricted diffusion on diffusion-weighted images. On images obtained during the portal venous phase, the lesions had peripheral enhancement with central hypoenhancement. On images obtained 4 minutes after the administration of contrast material, the lesions had a ""cluster of grapes"" appearance. Mild splenomegaly was also detected.
Dr. Schiavoni: The patient was admitted to the hospital, and fine-needle aspiration and core biopsy of a right axillary lymph node were performed.
Dr. Ruth K. Foreman: Examination of the aspirate and biopsy specimen (Figure 3) revealed benign-appearing lymph-node tissue with normal architecture and associated necroinflammatory debris. There was no histologic evidence of cancer. Acid-fast, Gomori methenamine-silver, periodic acid-Schiff, Brown-Hopps, and Steiner stains for microorganisms were negative, as was an immunohistochemical stain for spirochetes. Tissue from the biopsy was sent to the microbiology laboratory for culture.	
Figure 3 
Dr. Schiavoni: Additional diagnostic tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Bartonella henselae infection (Cat Scratch Disease). The patient's symptoms of abdominal pain, rash, and lymphadenopathy, along with the history of living in Morocco and visiting a rural village, suggest a possible infectious disease. The presence of erythematous, follicular papules and hyperpigmented nodules on the skin, as well as the histopathological findings of acute neutrophilic folliculitis, suggest a bacterial infection. The patient's symptoms did not improve with antibiotics, suggesting a possible resistant or atypical bacteria. The presence of hepatosplenic lesions and lymphadenopathy are characteristic of Bartonella henselae infection, also known as Cat Scratch Disease. This is further supported by the patient's history of living in a rural area where he may have been exposed to cats.""
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        ""content"": ""The patient's symptoms include abdominal pain, rash, and lymphadenopathy. He has a history of a persistent rash that has not responded to antibiotics, suggesting it may not be a simple bacterial infection. The patient also has a history of weight loss and night sweats, which are symptoms often associated with chronic diseases such as cancer or infections like tuberculosis. However, the patient's biopsy results showed no evidence of cancer. The patient also tested negative for HIV and hepatitis C, but tested positive for antibodies to hepatitis B virus surface antigen and antibodies to HBV core antigen, indicating a past or current infection. The patient's abdominal pain and the imaging results showing multiple abnormalities in the liver suggest a liver-related issue. Given the patient's history and symptoms, the most likely diagnosis is a chronic hepatitis B infection that has led to liver disease. \n\nDiagnosis: Chronic Hepatitis B with Liver Disease.""
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        ""content"": ""This is a 36-year-old man who presents with abdominal pain, rash, and lymphadenopathy. He has a history of a persistent neck swelling, a diffuse, erythematous, papular rash that evolved into hyperpigmented nodules, and recent development of right upper quadrant abdominal pain. He also reports weight loss and increased fatigue. The differential diagnosis for this patient includes lymphoma, sarcoidosis, tuberculosis, fungal infection, and brucellosis. The patient's biopsy of the lymph node and skin did not show any evidence of malignancy, making lymphoma less likely. The patient's biopsy also did not show any granulomas, making sarcoidosis less likely. The patient's acid-fast stain was negative, making tuberculosis less likely. The patient's Gomori methenamine-silver stain was negative, making a fungal infection less likely. The patient has a history of travel to a rural village in Morocco, a known endemic area for brucellosis. Brucellosis can present with lymphadenopathy, hepatosplenomegaly, and a rash. The patient's presentation is consistent with brucellosis. \n\nDiagnosis: Brucellosis is the most likely diagnosis.""
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10.1056/NEJMcpc1802833,Case 1-2019: A 34-Year-Old Veteran with Multiple Somatic Symptoms,"Hemoglobin (g/dl)   16.7 16.6
Hematocrit (%)   49.3 48.7
White-cell count (per mm3
) 4060–9400 7200 10,500
Platelet count (per mm3
) 124,00 35,000 307,000 338,000
Sodium (mmol/liter)   138 138
Potassium (mmol/liter)   4.5 3.9
Chloride (mmol/liter) 10 0 103 102
Carbon dioxide (mmol/liter) 2 0 26 26
Urea nitrogen (mg/dl) 7–25 12 11
Creatinine (mg/dl) 0.5–1.5 1.1 0.9
Glucose (mg/dl)   97 91
Aspartate aminotransferase (U/liter) 5–34 27 17
Alanine aminotransferase (U/liter) 7–52 62 21
Alkaline phosphatase (U/liter)   57 58
Thyrotropin (μIU/ml) 0.35–5.00 1.84 0.91
Cholesterol (mg/dl)
Total <199 236
High-density lipoprotein >40 36
Low-density lipoprotein 0–129 123
Triglycerides (mg/dl) <149 386
25-Hydroxyvitamin D (ng/ml) 20–50 24.3
Cortisol, morning (μg/dl) 6–28 6.9
Calcium (mg/dl)   10.4
Total protein (g/dl) 6. .5 8.0
Albumin (g/dl)   4.9
γ-Glutamyltransferase (U/liter) 10–65 24
Total bilirubin (mg/dl) 0.2–1.2 1.2
Lipase (IU/liter) 8–70 27
Glycated hemoglobin (%) 4.0–5.7 5.4",Post-traumatic stress disorder.,"Post-traumatic stress disorder.

Traumatic brain injury with secondary neurocognitive disorder.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 34-year-old man was evaluated at this hospital because of headaches, cognitive changes, mood symptoms, flashbacks, chest pain, arm tingling, and gastrointestinal symptoms. The patient had served as a special operations combat medic in the U.S. Army Rangers for 8 years. He served in Operation Iraqi Freedom, completing three tours of duty.
The patient had had multiple traumatic injuries and experiences during training and deployment. Nine years before the current evaluation, during a parachute-jump training, he had a syncopal episode. Afterward, he could recall only that he had awoken on the ground while a colleague was packing his parachute. He had 3 weeks of headaches, stiffness of the cervical and thoracic spine, and difficulty sleeping.
Eight years before the current evaluation, the patient was hit by an explosive blast wave. Afterward, he reported ""cloudy"" mentation. While he served as the company medic, he was a first responder in two cases in which a soldier had committed suicide.
Three years later, during his third deployment, the patient was involved in a motor vehicle accident as a helmeted back-seat passenger. The armored fighting vehicle rolled approximately 9 m into a canal, and the patient was pinned under several men. He had blunt trauma to the head and reportedly lost consciousness for 20 minutes; he had a concussion and traumatic injuries of the head and face, including a hard-palate fracture. He subsequently had headaches and difficulty eating and breathing because of lip and nose swelling.
In the years after that accident, two types of headache persisted. The patient described the first type of headache as bitemporal pain, above the ears, that occurred a few times per week and was pounding in quality, triggered by certain noises or emotional conversations, and associated with nausea; he used rizatriptan for relief. He described the second type of headache as a ""sharp, electrical"" sensation, generally in the posterior occiput, that was constant and associated with neck pain on turning of the head, sonophobia, photophobia, and nausea; he received botulinum toxin injections for temporary relief.
After the patient's third deployment ended, his wife noticed that he placed kitchen items in the wrong location, became lost while grocery shopping, and was unable to recall the birth of his first daughter. The patient expressed difficulty adjusting to a postdeployment routine, which included child care. He mentioned that he missed his level of entrusted responsibility in the Army Rangers platoon. He reported having ""deep, lingering pain at deaths of friends and exposures to children in dire circumstances"" and ""thinking philosophically about death"" but did not report suicidal or homicidal ideation. He rarely left the house except for appointments with doctors; he expressed difficulty making friends because he felt ""frustration with trivial topics,"" and he was self-conscious about being forgetful. Mood swings, headaches, emotional distance, personality changes, irritability, fluctuating appetite with intermittent nausea, and insomnia and poor sleep were also reported. He avoided such places as shopping malls because they made him feel dizzy. He started to consume large quantities of whiskey daily.
Between 3 and 5 years before the current evaluation, while the patient was still in the military, he sought medical and psychiatric care on three occasions. During the first evaluation, duloxetine was prescribed, but it resulted in a rash and peeling of the skin. Three years before the current evaluation, he received inpatient treatment at a military hospital, which included psychotherapy sessions and muscle relaxation and breathing exercises. Two years before the current evaluation, various medications - including sumatriptan, ibuprofen, prednisone, topiramate, and amitriptyline - were tried, with varying degrees of success.
Twenty-two months before the current evaluation, the patient was honorably discharged from the military, and he moved to New England. Thirteen months before the current evaluation, his condition was assessed by a social worker, psychologist, physical therapist, and neurologist at another hospital. He reported being ""constantly on guard"" and ""easily startled,"" as well as having anhedonia, detachment, difficulty concentrating, anorexia, and fatigue. He reported using sarcasm, defensiveness, and intellectualization as coping mechanisms. A review of systems was notable for a reduced ability to move the head and neck to the left and ""clicking"" with motion of the neck, both of which diminished modestly with physical therapy. Laboratory test results are shown in Table 1. The patient underwent a 3-month course of outpatient psychotherapy but then stopped because of a lack of connection with his provider.	
Table 1 
Five months before the current evaluation, the patient reported having flashbacks with associated emesis. The next month, he reported that his previous concussion was ""acting up."" He described having a ""hazy"" feeling, verbal stuttering, and severe headaches, which he rated at 10 on a scale of 0 to 10 (with 10 indicating the most severe pain). The headaches lasted for days and were associated with sonophobia and photophobia; he used ice and ibuprofen for relief. He also began to have panic attacks in association with recall of memories. He described having a ""rush of visions"" of traumatic memories from childhood and the military and being ""not able to turn them off""; lorazepam was prescribed. Recurrent pain and tingling of the left anterior chest and left anterior arm developed in association with these memories and later occurred independently of the memories. The patient treated himself for these symptoms with fans, cold baths, and benzodiazepines.
Two months before the current evaluation, multiple gastrointestinal symptoms developed. The patient had nonbloody, nonbilious emesis every morning, as well as persistent nausea, upper abdominal pain that was worse after eating, loose bowel movements alternating with constipation, difficulty initiating bowel movements, and eructation. He unintentionally lost 9 kg. He received prescriptions for tricyclic antidepressants, ondansetron, simethicone, and omeprazole for presumed irritable bowel syndrome. The next month, he had panic attacks of increased frequency and intensity and progressive symptoms, including atypical chest discomfort, heartburn, nausea, vomiting, and arm tingling. He sought attention in a local emergency department for panic attacks and fear that his heart was ""feeling weak."" Laboratory test results are shown in Table 1.
The patient was referred to this hospital; additional history was obtained from his wife. He had a history of obstructive sleep apnea, for which nightly continuous positive airway pressure had been prescribed, and he had undergone photorefractive keratectomy. A review of systems also revealed intrusive thoughts, hypervigilance, irritability, depressed mood, low energy, a feeling of burdening his family, and palpitations that were associated with anxiety and diffuse myalgia. He had no dizziness, ataxia, vision changes, sensory dysfunction, hallucinations, repetitive behaviors, or focal weakness. He did not drive because of feelings of panic. He wore a hearing aid because of difficulty discriminating speech in the presence of background noise. He used a traction device for treatment of neck strain.
The patient's father had depression, and his mother, father, and paternal uncle each had a history of alcohol and drug use disorders. The patient had been raised by his grandparents. A sister had died in her 20s from bone cancer. The patient lived with his wife and two healthy young children. He had not worked outside the home since his honorable discharge from the military, instead performing child care duties while his wife worked. He had completed 3 years of college; he had thought about additional schooling but felt discouraged because of forgetfulness. The patient had used chewing tobacco in the past but had not used any in 2 years. He consumed up to four caffeinated drinks daily and had only three or four alcoholic drinks monthly, which was a reduction from his past alcohol consumption. He smoked marijuana daily but used no illicit drugs. Medications included nortriptyline, omeprazole, pantoprazole, sucralfate, ondansetron, and as needed, simethicone.
On examination, the temperature was 37.1[degrees]C, the heart rate 94 beats per minute, the blood pressure 109/74 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 86 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 26.4. The patient was well groomed, alert, cooperative, oriented, and lucid, with coherent speech. He was described as fidgeting, anxious, and irritable. The remainder of the cardiovascular, pulmonary, abdominal, and musculoskeletal examination was normal. A urine toxicology screen was positive for cannabinoids and negative for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, and phencyclidine.
A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 34-year-old man was evaluated at this hospital because of headaches, cognitive changes, mood symptoms, flashbacks, chest pain, arm tingling, and gastrointestinal symptoms. The patient had served as a special operations combat medic in the U.S. Army Rangers for 8 years. He served in Operation Iraqi Freedom, completing three tours of duty.
The patient had had multiple traumatic injuries and experiences during training and deployment. Nine years before the current evaluation, during a parachute-jump training, he had a syncopal episode. Afterward, he could recall only that he had awoken on the ground while a colleague was packing his parachute. He had 3 weeks of headaches, stiffness of the cervical and thoracic spine, and difficulty sleeping.
Eight years before the current evaluation, the patient was hit by an explosive blast wave. Afterward, he reported ""cloudy"" mentation. While he served as the company medic, he was a first responder in two cases in which a soldier had committed suicide.
Three years later, during his third deployment, the patient was involved in a motor vehicle accident as a helmeted back-seat passenger. The armored fighting vehicle rolled approximately 9 m into a canal, and the patient was pinned under several men. He had blunt trauma to the head and reportedly lost consciousness for 20 minutes; he had a concussion and traumatic injuries of the head and face, including a hard-palate fracture. He subsequently had headaches and difficulty eating and breathing because of lip and nose swelling.
In the years after that accident, two types of headache persisted. The patient described the first type of headache as bitemporal pain, above the ears, that occurred a few times per week and was pounding in quality, triggered by certain noises or emotional conversations, and associated with nausea; he used rizatriptan for relief. He described the second type of headache as a ""sharp, electrical"" sensation, generally in the posterior occiput, that was constant and associated with neck pain on turning of the head, sonophobia, photophobia, and nausea; he received botulinum toxin injections for temporary relief.
After the patient's third deployment ended, his wife noticed that he placed kitchen items in the wrong location, became lost while grocery shopping, and was unable to recall the birth of his first daughter. The patient expressed difficulty adjusting to a postdeployment routine, which included child care. He mentioned that he missed his level of entrusted responsibility in the Army Rangers platoon. He reported having ""deep, lingering pain at deaths of friends and exposures to children in dire circumstances"" and ""thinking philosophically about death"" but did not report suicidal or homicidal ideation. He rarely left the house except for appointments with doctors; he expressed difficulty making friends because he felt ""frustration with trivial topics,"" and he was self-conscious about being forgetful. Mood swings, headaches, emotional distance, personality changes, irritability, fluctuating appetite with intermittent nausea, and insomnia and poor sleep were also reported. He avoided such places as shopping malls because they made him feel dizzy. He started to consume large quantities of whiskey daily.
Between 3 and 5 years before the current evaluation, while the patient was still in the military, he sought medical and psychiatric care on three occasions. During the first evaluation, duloxetine was prescribed, but it resulted in a rash and peeling of the skin. Three years before the current evaluation, he received inpatient treatment at a military hospital, which included psychotherapy sessions and muscle relaxation and breathing exercises. Two years before the current evaluation, various medications - including sumatriptan, ibuprofen, prednisone, topiramate, and amitriptyline - were tried, with varying degrees of success.
Twenty-two months before the current evaluation, the patient was honorably discharged from the military, and he moved to New England. Thirteen months before the current evaluation, his condition was assessed by a social worker, psychologist, physical therapist, and neurologist at another hospital. He reported being ""constantly on guard"" and ""easily startled,"" as well as having anhedonia, detachment, difficulty concentrating, anorexia, and fatigue. He reported using sarcasm, defensiveness, and intellectualization as coping mechanisms. A review of systems was notable for a reduced ability to move the head and neck to the left and ""clicking"" with motion of the neck, both of which diminished modestly with physical therapy. Laboratory test results are shown in Table 1. The patient underwent a 3-month course of outpatient psychotherapy but then stopped because of a lack of connection with his provider.	
Table 1 
Five months before the current evaluation, the patient reported having flashbacks with associated emesis. The next month, he reported that his previous concussion was ""acting up."" He described having a ""hazy"" feeling, verbal stuttering, and severe headaches, which he rated at 10 on a scale of 0 to 10 (with 10 indicating the most severe pain). The headaches lasted for days and were associated with sonophobia and photophobia; he used ice and ibuprofen for relief. He also began to have panic attacks in association with recall of memories. He described having a ""rush of visions"" of traumatic memories from childhood and the military and being ""not able to turn them off""; lorazepam was prescribed. Recurrent pain and tingling of the left anterior chest and left anterior arm developed in association with these memories and later occurred independently of the memories. The patient treated himself for these symptoms with fans, cold baths, and benzodiazepines.
Two months before the current evaluation, multiple gastrointestinal symptoms developed. The patient had nonbloody, nonbilious emesis every morning, as well as persistent nausea, upper abdominal pain that was worse after eating, loose bowel movements alternating with constipation, difficulty initiating bowel movements, and eructation. He unintentionally lost 9 kg. He received prescriptions for tricyclic antidepressants, ondansetron, simethicone, and omeprazole for presumed irritable bowel syndrome. The next month, he had panic attacks of increased frequency and intensity and progressive symptoms, including atypical chest discomfort, heartburn, nausea, vomiting, and arm tingling. He sought attention in a local emergency department for panic attacks and fear that his heart was ""feeling weak."" Laboratory test results are shown in Table 1.
The patient was referred to this hospital; additional history was obtained from his wife. He had a history of obstructive sleep apnea, for which nightly continuous positive airway pressure had been prescribed, and he had undergone photorefractive keratectomy. A review of systems also revealed intrusive thoughts, hypervigilance, irritability, depressed mood, low energy, a feeling of burdening his family, and palpitations that were associated with anxiety and diffuse myalgia. He had no dizziness, ataxia, vision changes, sensory dysfunction, hallucinations, repetitive behaviors, or focal weakness. He did not drive because of feelings of panic. He wore a hearing aid because of difficulty discriminating speech in the presence of background noise. He used a traction device for treatment of neck strain.
The patient's father had depression, and his mother, father, and paternal uncle each had a history of alcohol and drug use disorders. The patient had been raised by his grandparents. A sister had died in her 20s from bone cancer. The patient lived with his wife and two healthy young children. He had not worked outside the home since his honorable discharge from the military, instead performing child care duties while his wife worked. He had completed 3 years of college; he had thought about additional schooling but felt discouraged because of forgetfulness. The patient had used chewing tobacco in the past but had not used any in 2 years. He consumed up to four caffeinated drinks daily and had only three or four alcoholic drinks monthly, which was a reduction from his past alcohol consumption. He smoked marijuana daily but used no illicit drugs. Medications included nortriptyline, omeprazole, pantoprazole, sucralfate, ondansetron, and as needed, simethicone.
On examination, the temperature was 37.1[degrees]C, the heart rate 94 beats per minute, the blood pressure 109/74 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 86 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 26.4. The patient was well groomed, alert, cooperative, oriented, and lucid, with coherent speech. He was described as fidgeting, anxious, and irritable. The remainder of the cardiovascular, pulmonary, abdominal, and musculoskeletal examination was normal. A urine toxicology screen was positive for cannabinoids and negative for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, and phencyclidine.
A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's history of military service, traumatic experiences, and symptoms such as headaches, cognitive changes, mood symptoms, flashbacks, chest pain, arm tingling, and gastrointestinal symptoms suggest a psychological disorder. The patient's symptoms of being \""constantly on guard\"", \""easily startled\"", detachment, difficulty concentrating, anhedonia, and fatigue are indicative of post-traumatic stress disorder (PTSD). The patient's history of traumatic experiences during his military service, including exposure to explosive blast waves and being a first responder in cases of suicide, are traumatic events that can lead to PTSD. The patient's symptoms of flashbacks, panic attacks, and intrusive thoughts are characteristic of PTSD. The patient's avoidance of places like shopping malls because they make him feel dizzy, his difficulty making friends because of his frustration with trivial topics, and his self-consciousness about being forgetful are indicative of the avoidance symptoms of PTSD. The patient's irritability, mood swings, and difficulty sleeping are indicative of the arousal and reactivity symptoms of PTSD. The patient's cognitive changes, such as difficulty remembering the birth of his first daughter and placing kitchen items in the wrong location, are indicative of the cognition and mood symptoms of PTSD. Therefore, the patient's symptoms and history are consistent with a diagnosis of PTSD.\n\nDiagnosis: Post-Traumatic Stress Disorder (PTSD)""
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}",Post-traumatic stress disorder (PTSD),Y,"{
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        ""content"": ""The patient is a 34-year-old male with a history of multiple traumatic experiences and injuries during his military service, including a concussion and blunt trauma to the head. He presents with headaches, cognitive changes, mood symptoms, flashbacks, chest pain, arm tingling, and gastrointestinal symptoms. The differential diagnosis for this patient includes post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and somatic symptom disorder. \n\nThe patient's symptoms of being \""constantly on guard,\"" \""easily startled,\"" anhedonia, detachment, difficulty concentrating, and having flashbacks of traumatic memories are consistent with PTSD. His history of multiple traumatic experiences during his military service, including being a first responder in two cases of suicide and being hit by an explosive blast wave, further supports this diagnosis. \n\nThe patient's headaches, \""cloudy\"" mentation, and reported difficulty with memory and cognitive function could be indicative of a TBI. His history of a concussion and blunt trauma to the head during his military service supports this diagnosis. \n\nThe patient's chest pain, arm tingling, and gastrointestinal symptoms could be indicative of somatic symptom disorder. However, these symptoms could also be related to his PTSD or TBI. \n\nGiven the patient's history and symptoms, PTSD is the most likely diagnosis. His symptoms of being \""constantly on guard,\"" \""easily startled,\"" anhedonia, detachment, difficulty concentrating, and having flashbacks of traumatic memories are all characteristic of PTSD. His history of multiple traumatic experiences during his military service further supports this diagnosis. \n\nDiagnosis: Post-traumatic stress disorder (PTSD)""
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10.1056/NEJMcpc1810388,"Case 40-2018: A 47-Year-Old Woman with Recurrent Sinusitis, Cough, and Bronchiectasis","Hemoglobin (g/dl)   13.3
Hematocrit (%)   38.3
White-cell count (per mm3)   10,800
Differential count (%)
Neutrophils   81
Lymphocytes   10
Monocytes   6
Eosinophils   3
Basophils   0
Platelet count (per mm3) 150,00 50,000 272,000
Sodium (mmol/liter)   140
Potassium (mmol/liter)   4.3
Chloride (mmol/liter)   96
Carbon dioxide (mmol/liter) 23. 1.9 26
Urea nitrogen (mg/dl)   8
Creatinine (mg/dl)   0.7
Glucose (mg/dl)   87
Calcium (mg/dl)   9.3
Total protein (g/dl) 6. .3 7.4
Albumin (g/dl)   4.1
Globulin (g/dl)   3.3
Alanine aminotransferase (U/liter) 7–30 19
Aspartate aminotransferase (U/liter)   21
Alkaline phosphatase (U/liter)   71
Total bilirubin (mg/dl)  0.4
Erythrocyte sedimentation rate (mm/hr)  28",Cystic fibrosis due to compound heterozygous CFTR Phe508del and D1152H mutations.,Cystic fibrosis (nonclassic) or primary ciliary dyskinesia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 47-year-old woman was evaluated at the outpatient pulmonary clinic of this hospital because of recurrent sinusitis with progressive cough and bronchiectasis.
Since her mid-20s, the patient had had recurrent episodes of sinus congestion, with two or three sinus infections annually, which had prompted treatment with multiple courses of antibiotics. When she was approximately 30 years of age, she was evaluated by an otorhinologist at another hospital, who suggested the possibility of an allergic trigger. Skin testing revealed environmental allergies, to dust, grass, and cats. Blood testing revealed allergies to multiple foods, including milk, yeast, wheat, gluten, rye, and egg white. Elimination of milk, grains, and eggs from her diet resulted in a reduction in sinus symptoms for approximately 5 years. However, sinus congestion and sinus infections recurred in subsequent years. Three years before the current evaluation, a persistent cough developed. The patient was evaluated at a second hospital; she received a diagnosis of bacterial pneumonia and was treated. Thereafter, she was referred to a third hospital for sinus surgery with turbinectomy.
Approximately 6 months before the current evaluation, the patient noted the onset of daily production of yellowish-white sputum. The amount of sputum increased, and the sputum occasionally appeared green. Two months later, the patient was evaluated by her primary care physician at the second hospital. Chest radiography was notable for bronchiectasis, predominantly in the upper and middle lung zones.
A sputum culture reportedly grew Enterobacter cloacae, Serratia marcescens, and Mycobacterium abscessus. A complete blood count and results of kidney- and liver-function tests were normal. The blood level of IgE was normal (5 IU per milliliter; reference range, 0 to 158), as was the alpha1-antitrypsin level (146 mg per deciliter; reference range, 100 to 190). A test for antineutrophil cytoplasmic antibody was negative, as was radioallergosorbent testing for environmental allergens that are common in the northeastern United States. Pulmonary-function testing reportedly revealed a forced expiratory volume in 1 second (FEV1) of 2.22 liters (80% of the predicted value), a forced vital capacity (FVC) of 2.72 liters (81% of the predicted value), and a ratio of FEV1 to FVC of 82%. The total lung capacity was normal, but the ratio of residual volume to total lung capacity was elevated, at 45% (predicted value, 35%). The diffusion capacity for carbon monoxide was normal. Inhaled fluticasone propionate-salmeterol and levofloxacin were administered, and the cough diminished temporarily. Additional courses of levofloxacin were prescribed for recurrent cough and sputum production during the next 4 months, until the patient was evaluated in the pulmonary clinic of this hospital.
During her evaluation in the pulmonary clinic, the patient reported mild but increasing dyspnea on exertion and progressive fatigue. She had persistent sinus congestion and occasional headaches. She had no history of asthma, heart-failure symptoms, hemoptysis, fevers, chills, night sweats, weight loss, myalgias, arthralgias, rash, or gastrointestinal symptoms. She reported no sick contacts and had no known exposure to tuberculosis.
The patient had a history of migraines. She had undergone tonsillectomy in the remote past, uterine polypectomy 3 years earlier, bilateral laser-assisted in situ keratomileusis 4 years earlier, and removal of a benign breast mass 8 years earlier. Her medications included inhaled fluticasone propionate-salmeterol and over-the-counter guaifenesin-phenylephrine. She had no known allergies to medications. She had never smoked and did not drink alcohol or use illicit drugs. She was engaged to be married and had no children. She lived in Massachusetts, and her travel history included trips to Canada and the Caribbean. She worked in an office and had no known occupational or inhalational exposures; she had no animal exposures, although she enjoyed gardening. Her father had had prostate cancer, coronary artery disease, and a stroke, and her mother had had coronary artery disease and had undergone a thyroidectomy for a benign nodule. Her brother had allergic rhinitis, and her sister was healthy.
The patient appeared to be well and comfortable. The respiratory rate was 14 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. The height was 165 cm, the weight 64 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 23.5. There was no tenderness on sinus percussion. Crackles were present at the right apex on lung auscultation. There was no clubbing, and the remainder of the examination was normal. Laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1
Dr. Jad S. Husseini: Posteroanterior and lateral radiographs of the chest showed ""tram track"" opacities that involved both upper lung zones and the left lower lung zone, a finding consistent with bronchiectasis. The lung volumes were normal. There was no consolidative opacity or evidence of pulmonary edema, pleural effusion, or mediastinal or hilar lymphadenopathy (Figure 1).	
Figure 1 
Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, revealed bronchiectasis that involved all lobes of the lung but was most severe in the right upper lobe. Areas of mucous plugging were present in airways in the upper lobes. There were scattered ""tree in bud"" opacities, as well as multiple scattered solid pulmonary nodules, measuring up to 1.5 cm in diameter. There was no evidence of pulmonary edema, pleural effusion, or mediastinal or hilar lymphadenopathy (Figure 2).	
Figure 2 
Dr. Richards: Examination of a sputum sample revealed 3+ to 4+ acid-fast bacilli, along with occasional polymorphonuclear leukocytes and a few gram-positive bacteria.
Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 47-year-old woman was evaluated at the outpatient pulmonary clinic of this hospital because of recurrent sinusitis with progressive cough and bronchiectasis.
Since her mid-20s, the patient had had recurrent episodes of sinus congestion, with two or three sinus infections annually, which had prompted treatment with multiple courses of antibiotics. When she was approximately 30 years of age, she was evaluated by an otorhinologist at another hospital, who suggested the possibility of an allergic trigger. Skin testing revealed environmental allergies, to dust, grass, and cats. Blood testing revealed allergies to multiple foods, including milk, yeast, wheat, gluten, rye, and egg white. Elimination of milk, grains, and eggs from her diet resulted in a reduction in sinus symptoms for approximately 5 years. However, sinus congestion and sinus infections recurred in subsequent years. Three years before the current evaluation, a persistent cough developed. The patient was evaluated at a second hospital; she received a diagnosis of bacterial pneumonia and was treated. Thereafter, she was referred to a third hospital for sinus surgery with turbinectomy.
Approximately 6 months before the current evaluation, the patient noted the onset of daily production of yellowish-white sputum. The amount of sputum increased, and the sputum occasionally appeared green. Two months later, the patient was evaluated by her primary care physician at the second hospital. Chest radiography was notable for bronchiectasis, predominantly in the upper and middle lung zones.
A sputum culture reportedly grew Enterobacter cloacae, Serratia marcescens, and Mycobacterium abscessus. A complete blood count and results of kidney- and liver-function tests were normal. The blood level of IgE was normal (5 IU per milliliter; reference range, 0 to 158), as was the alpha1-antitrypsin level (146 mg per deciliter; reference range, 100 to 190). A test for antineutrophil cytoplasmic antibody was negative, as was radioallergosorbent testing for environmental allergens that are common in the northeastern United States. Pulmonary-function testing reportedly revealed a forced expiratory volume in 1 second (FEV1) of 2.22 liters (80% of the predicted value), a forced vital capacity (FVC) of 2.72 liters (81% of the predicted value), and a ratio of FEV1 to FVC of 82%. The total lung capacity was normal, but the ratio of residual volume to total lung capacity was elevated, at 45% (predicted value, 35%). The diffusion capacity for carbon monoxide was normal. Inhaled fluticasone propionate-salmeterol and levofloxacin were administered, and the cough diminished temporarily. Additional courses of levofloxacin were prescribed for recurrent cough and sputum production during the next 4 months, until the patient was evaluated in the pulmonary clinic of this hospital.
During her evaluation in the pulmonary clinic, the patient reported mild but increasing dyspnea on exertion and progressive fatigue. She had persistent sinus congestion and occasional headaches. She had no history of asthma, heart-failure symptoms, hemoptysis, fevers, chills, night sweats, weight loss, myalgias, arthralgias, rash, or gastrointestinal symptoms. She reported no sick contacts and had no known exposure to tuberculosis.
The patient had a history of migraines. She had undergone tonsillectomy in the remote past, uterine polypectomy 3 years earlier, bilateral laser-assisted in situ keratomileusis 4 years earlier, and removal of a benign breast mass 8 years earlier. Her medications included inhaled fluticasone propionate-salmeterol and over-the-counter guaifenesin-phenylephrine. She had no known allergies to medications. She had never smoked and did not drink alcohol or use illicit drugs. She was engaged to be married and had no children. She lived in Massachusetts, and her travel history included trips to Canada and the Caribbean. She worked in an office and had no known occupational or inhalational exposures; she had no animal exposures, although she enjoyed gardening. Her father had had prostate cancer, coronary artery disease, and a stroke, and her mother had had coronary artery disease and had undergone a thyroidectomy for a benign nodule. Her brother had allergic rhinitis, and her sister was healthy.
The patient appeared to be well and comfortable. The respiratory rate was 14 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. The height was 165 cm, the weight 64 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 23.5. There was no tenderness on sinus percussion. Crackles were present at the right apex on lung auscultation. There was no clubbing, and the remainder of the examination was normal. Laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1
Dr. Jad S. Husseini: Posteroanterior and lateral radiographs of the chest showed ""tram track"" opacities that involved both upper lung zones and the left lower lung zone, a finding consistent with bronchiectasis. The lung volumes were normal. There was no consolidative opacity or evidence of pulmonary edema, pleural effusion, or mediastinal or hilar lymphadenopathy (Figure 1).	
Figure 1 
Computed tomography (CT) of the chest, performed after the administration of intravenous contrast material, revealed bronchiectasis that involved all lobes of the lung but was most severe in the right upper lobe. Areas of mucous plugging were present in airways in the upper lobes. There were scattered ""tree in bud"" opacities, as well as multiple scattered solid pulmonary nodules, measuring up to 1.5 cm in diameter. There was no evidence of pulmonary edema, pleural effusion, or mediastinal or hilar lymphadenopathy (Figure 2).	
Figure 2 
Dr. Richards: Examination of a sputum sample revealed 3+ to 4+ acid-fast bacilli, along with occasional polymorphonuclear leukocytes and a few gram-positive bacteria.
Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's history of recurrent sinusitis, bronchiectasis, and the presence of Mycobacterium abscessus in her sputum culture suggest a diagnosis of a non-tuberculous mycobacterial (NTM) infection. NTM infections are often associated with structural lung diseases like bronchiectasis. The patient's symptoms have been progressively worsening, which is consistent with the chronic nature of NTM infections. The presence of \""tree in bud\"" opacities on the CT scan is also a common finding in NTM infections. Therefore, the most likely diagnosis is a non-tuberculous mycobacterial infection.""
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        ""content"": ""The patient is a 47-year-old woman with a history of recurrent sinusitis and bronchiectasis. She has a history of environmental and food allergies. She has been having recurrent sinus infections and has been treated with multiple courses of antibiotics. She has also developed a persistent cough and has been producing yellowish-white sputum. Her chest radiography showed bronchiectasis, predominantly in the upper and middle lung zones. A sputum culture grew Enterobacter cloacae, Serratia marcescens, and Mycobacterium abscessus. Her pulmonary function tests showed a reduced FEV1 and FVC, but a normal total lung capacity. Her symptoms, along with her history and test results, suggest a few possible diagnoses. These include cystic fibrosis, primary ciliary dyskinesia, and non-cystic fibrosis bronchiectasis. Cystic fibrosis is a genetic disorder that affects the lungs and digestive system. It causes thick, sticky mucus to build up in the lungs, leading to lung infections and damage. However, the patient's age and lack of digestive symptoms make this diagnosis less likely. Primary ciliary dyskinesia is a genetic disorder that affects the movement of cilia in the lungs, leading to recurrent respiratory infections. However, this condition is usually diagnosed in childhood, making it less likely in this case. Non-cystic fibrosis bronchiectasis is a condition where the bronchi in the lungs are permanently damaged and widened. This can be caused by recurrent lung infections, immune system disorders, or inhaling a foreign object or harmful substance. Given the patient's history of recurrent sinus infections and the findings on her chest radiography, this seems to be the most likely diagnosis. \nDiagnosis: Non-cystic fibrosis bronchiectasis.""
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10.1056/NEJMcpc1807503,Case 39-2018: An 18-Year-Old Man with Diplopia and Proptosis of the Left Eye,"Hematocrit (%) 47.2   48.7
Hemoglobin (g/dl)  15.8   16.6
White-cell count (per mm3) 430 ,000 15,100 450 ,000 13,790
Differential count (%)
Neutrophils 84.5  61.3
Immature granulocytes 1.8   1.0
Lymphocytes 7.0  29.5
Monocytes 6.4   7.4
Basophils 0.2   0.3
Eosinophils 0.1   0.5
Platelet count (per mm3
) 159,00 59,000 379,000   373,000
Red-cell count (per mm3
)  5,240,000   5,400,000
Mean corpuscular volume (fl)  90.1   90.2
Mean corpuscular hemoglobin (pg) 26. .5 30.2 26. 4.0 30.7
Mean corpuscular hemoglobin concentration (g/dl) 32.1–35.9 33.5 31. 7.0 34.1
Red-cell distribution width (%) 11.9–13.9 13.8   14.2
Erythrocyte sedimentation rate (mm/hr)  0 3
Sodium (mmol/liter)   139   143
Potassium (mmol/liter) 3.5–5.5 3.8   3.4
Chloride (mmol/liter) 96–108 101   100
Carbon dioxide (mmol/liter) 18–30 22   23
Calcium (mg/dl)   9.7   9.6
Anion gap (mmol/liter) 5–16 16   20
Urea nitrogen (mg/dl) 5–20 15   9
Creatinine (mg/dl) 0.50–1.20 0.82   0.91
Estimated glomerular filtration rate (ml/min/1.73 m2
)‡ >60 >60 >60 >60
Glucose (mg/dl) 70–100 122   86
Alanine aminotransferase (U/liter) 0–50 38   35
Aspartate aminotransferase (U/liter) 0–45 11   13
Alkaline phosphatase (U/liter) 53–238 76 15–350 74
Total bilirubin (mg/dl) 0.1–1.5 0.3  0.4
Protein (g/dl)
Total 6.7–8.4 6.8 6. .3 7.7
Albumin 4.2–5.3 4.4   4.5
Globulin   3.2
Cholesterol (mg/dl)
Total <200 193
High-density lipoprotein   52
Low-density lipoprotein   121
Triglycerides (mg/dl)   100                                                                              Glycated hemoglobin (%) 4.3–6.4 5.1
Thyrotropin (μIU/ml) 0.30 00 0.493
C3 (mg/dl) 81–157 157
C4 (mg/dl) 12–39 31
IgG (mg/dl) 672–1680 705   681
IgG1 (mg/dl) 315–855 504 382.4–928.6 453
IgG2 (mg/dl) 64–495 153 241.8–700.3 158.7
IgG3 (mg/dl) 23–196 20 21.8–176.1 17.7
IgG4 (mg/dl)  7 14 3.9–86.4 15.7
IgA (mg/dl)   118
IgM (mg/dl)   86
IgE (IU/ml) 0–100 310
Serum protein electrophoresis Normal pattern
Antineutrophil cytoplasmic antibodies Negative Negative
Hepatitis B core antibody, total Negative Negative
Interferon-γ release assay for Mycobacterium tuberculosis Negative Negative",Granulomatosis with polyangiitis.,"Primary orbital inflammation, most likely granulomatosis with polyangiitis, although sarcoidosis and IgG4-related disease cannot be ruled out.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 18-year-old man was evaluated at this hospital because of diplopia and proptosis of the left eye.
The patient had been well until approximately 33 months before this evaluation, when eye pain and periorbital swelling developed on the right side. The pain was constant, and the use of ophthalmic ketotifen fumarate did not provide relief. On the eighth day of illness, the patient was seen in the ophthalmology clinic at another hospital. Examination revealed visual acuity of 20/25 in the right eye and 20/30 in the left eye, along with 3 mm of proptosis of the right eye and swelling, erythema, and ptosis of the right eyelid. Ophthalmic fluorometholone and oral doxycycline were prescribed.
Five days later, the patient returned to the ophthalmology clinic and reported a 1-day history of fuzzy vision in the right eye. He had persistent proptosis, ptosis, and eyelid swelling. On examination of the right eye, visual acuity was 20/50 and there was a new superior visual-field defect in response to confrontation. Extraocular motility was normal. Three days after this visit, magnetic resonance imaging (MRI) of the orbits, performed after the intravenous administration of contrast material, revealed mild-to-moderate enlargement of the inferior, medial, and superior rectus muscles in the right orbit, which had resulted in narrowing of the posterior orbital apex. There was enhancement of the enlarged extraocular muscles, as well as abnormal hyperintense signal on T2-weighted images. Concurrent MRI of the head was normal, as were blood levels of thyrotropin and free thyroxine. Prednisone (40 mg per day) was prescribed.
During the next 2 weeks, the pain and eyelid swelling diminished and the visual acuity normalized, but the proptosis and visual-field restriction persisted. The patient also had decreased color vision in the right eye, without a relative afferent pupillary defect. The dose of prednisone was decreased to 20 mg per day; after 2 weeks of this dosing regimen, the proptosis and ptosis persisted but the remainder of the ophthalmologic examination was normal. The dose of prednisone was gradually decreased over a period of 7.5 months and then stopped; symptoms resolved and the ophthalmologic examination was normal.
Seven months after discontinuation of prednisone (17 months before this evaluation), the patient returned to the ophthalmology clinic because of a 1-week history of recurrent eye pain and periorbital swelling on the right side. Prednisone was administered for 5 days at a dose of 40 mg per day and then was continued at a dose of 20 mg per day. During the next 2.5 weeks, the pain persisted and the swelling worsened. The dose of prednisone was increased to 60 mg per day, and oral methotrexate and folic acid were prescribed; the pain and swelling diminished. The dose of prednisone was gradually decreased during the next 2.5 months and then stopped.
One month later (13 months before this evaluation), the pain in the right eye recurred and the patient returned to the ophthalmology clinic. Prednisone (40 mg per day) was prescribed, and the dose of methotrexate was increased. During the next 3 months, pain recurred each time the dose of prednisone was decreased to 20 mg per day; naproxen was prescribed.
Ten months before this evaluation, the patient was seen in the rheumatology clinic at the other hospital. He reported weight gain but no fever, fatigue, eye pain, vision problems, dry eyes, dry mouth, oral or nasal ulcerations, shortness of breath, arthralgias, or rash. On examination, he had a cushingoid appearance and was in no apparent distress. The vital signs were normal. The body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 29.7. There was no conjunctival injection, and extraocular motility was normal. He did not have thyromegaly, lymphadenopathy, rash, or synovitis; the remainder of the examination was normal. Laboratory test results are shown in Table 1. Prednisone and folic acid were continued, and oral methotrexate was changed to subcutaneous methotrexate. During the next 4 months, the dose of prednisone was gradually decreased to 2.5 mg per day, without recurrence of pain. The alanine aminotransferase level increased to 81 U per liter (reference range, 0 to 50); the dose of methotrexate was decreased, and the level normalized.	
Table 1 
Four months before this evaluation, pressure-type pain developed in the left eye. On examination at the rheumatology clinic, the blood pressure was 129/77 mm Hg and the other vital signs were normal. The BMI was 30.7. The patient had a cushingoid body habitus and facial acne. He did not have proptosis or eyelid edema. Extraocular motility was normal, as was the remainder of the examination. The dose of subcutaneous methotrexate was increased, and the dose of prednisone was increased to 20 mg per day. During the next 6 weeks, the pain in the left eye persisted, and periorbital swelling and proptosis developed on the left side. The dose of prednisone was increased to 40 mg per day, without improvement, and then to 60 mg per day. During this time, cellulitis of the right lower abdominal wall developed. A course of oral doxycycline was administered, followed by a course of oral cephalexin and topical mupirocin; methotrexate was discontinued. Eight weeks before this evaluation, the proptosis persisted. Mycophenolate mofetil was prescribed, and the dose of prednisone was decreased to 40 mg per day. The patient was referred to a rheumatologist and ophthalmologist at this hospital for further evaluation.
On evaluation in the ophthalmology and rheumatology clinics at this hospital, the patient reported proptosis and a 2-week history of diplopia in all directions of gaze, without pain. He had seasonal allergic rhinitis and a remote history of esotropia, asthma, tonsillectomy, adenoidectomy, and myringotomy. Nine months earlier, he had had an episode of bilateral submandibular sialadenitis; a test for mumps virus infection had been negative. Medications included prednisone, mycophenolate mofetil, cholecalciferol, and Saccharomyces boulardii. Ibuprofen had caused itching. The patient was a college student and lived in the southern central United States. He did not drink alcohol, smoke tobacco, or use illicit drugs. His grandmother had Graves' disease.
On examination, the patient had a cushingoid appearance. He had exotropia and minimal proptosis of the left eye, pallor of the right optic disk, and a right inferior central defect on visual-field testing. Examination of the skin revealed striae and acne (Figure 1). The remainder of the examination was normal. Laboratory test results are shown in Table 1. Urinalysis was normal; the urine protein level was 15.7 mg per deciliter (reference range, 0.0 to 13.5), and the urine protein:creatinine ratio was 0.05 (reference range, <0.15). Imaging studies were obtained.	
Figure 1 
Dr. Katherine L. Reinshagen: MRI of the orbits was performed (Figure 2). Contrast-enhanced T1-weighted images, obtained with and without fat suppression, showed abnormal fusiform enlargement and increased enhancement of the left medial and inferior rectus muscles, with a central area of hypoenhancement of the left medial rectus muscle. There was relative sparing of the musculotendinous insertions and no substantial surrounding fat stranding. In addition, T2-weighted images showed hyperintense signal in the left medial and inferior rectus muscles, a finding suggestive of edema. There was mild proptosis of the left globe. The right orbit and paranasal sinuses were essentially unremarkable.	
Figure 2 
Dr. Matza: A diagnostic procedure was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
An 18-year-old man was evaluated at this hospital because of diplopia and proptosis of the left eye.
The patient had been well until approximately 33 months before this evaluation, when eye pain and periorbital swelling developed on the right side. The pain was constant, and the use of ophthalmic ketotifen fumarate did not provide relief. On the eighth day of illness, the patient was seen in the ophthalmology clinic at another hospital. Examination revealed visual acuity of 20/25 in the right eye and 20/30 in the left eye, along with 3 mm of proptosis of the right eye and swelling, erythema, and ptosis of the right eyelid. Ophthalmic fluorometholone and oral doxycycline were prescribed.
Five days later, the patient returned to the ophthalmology clinic and reported a 1-day history of fuzzy vision in the right eye. He had persistent proptosis, ptosis, and eyelid swelling. On examination of the right eye, visual acuity was 20/50 and there was a new superior visual-field defect in response to confrontation. Extraocular motility was normal. Three days after this visit, magnetic resonance imaging (MRI) of the orbits, performed after the intravenous administration of contrast material, revealed mild-to-moderate enlargement of the inferior, medial, and superior rectus muscles in the right orbit, which had resulted in narrowing of the posterior orbital apex. There was enhancement of the enlarged extraocular muscles, as well as abnormal hyperintense signal on T2-weighted images. Concurrent MRI of the head was normal, as were blood levels of thyrotropin and free thyroxine. Prednisone (40 mg per day) was prescribed.
During the next 2 weeks, the pain and eyelid swelling diminished and the visual acuity normalized, but the proptosis and visual-field restriction persisted. The patient also had decreased color vision in the right eye, without a relative afferent pupillary defect. The dose of prednisone was decreased to 20 mg per day; after 2 weeks of this dosing regimen, the proptosis and ptosis persisted but the remainder of the ophthalmologic examination was normal. The dose of prednisone was gradually decreased over a period of 7.5 months and then stopped; symptoms resolved and the ophthalmologic examination was normal.
Seven months after discontinuation of prednisone (17 months before this evaluation), the patient returned to the ophthalmology clinic because of a 1-week history of recurrent eye pain and periorbital swelling on the right side. Prednisone was administered for 5 days at a dose of 40 mg per day and then was continued at a dose of 20 mg per day. During the next 2.5 weeks, the pain persisted and the swelling worsened. The dose of prednisone was increased to 60 mg per day, and oral methotrexate and folic acid were prescribed; the pain and swelling diminished. The dose of prednisone was gradually decreased during the next 2.5 months and then stopped.
One month later (13 months before this evaluation), the pain in the right eye recurred and the patient returned to the ophthalmology clinic. Prednisone (40 mg per day) was prescribed, and the dose of methotrexate was increased. During the next 3 months, pain recurred each time the dose of prednisone was decreased to 20 mg per day; naproxen was prescribed.
Ten months before this evaluation, the patient was seen in the rheumatology clinic at the other hospital. He reported weight gain but no fever, fatigue, eye pain, vision problems, dry eyes, dry mouth, oral or nasal ulcerations, shortness of breath, arthralgias, or rash. On examination, he had a cushingoid appearance and was in no apparent distress. The vital signs were normal. The body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 29.7. There was no conjunctival injection, and extraocular motility was normal. He did not have thyromegaly, lymphadenopathy, rash, or synovitis; the remainder of the examination was normal. Laboratory test results are shown in Table 1. Prednisone and folic acid were continued, and oral methotrexate was changed to subcutaneous methotrexate. During the next 4 months, the dose of prednisone was gradually decreased to 2.5 mg per day, without recurrence of pain. The alanine aminotransferase level increased to 81 U per liter (reference range, 0 to 50); the dose of methotrexate was decreased, and the level normalized.	
Table 1 
Four months before this evaluation, pressure-type pain developed in the left eye. On examination at the rheumatology clinic, the blood pressure was 129/77 mm Hg and the other vital signs were normal. The BMI was 30.7. The patient had a cushingoid body habitus and facial acne. He did not have proptosis or eyelid edema. Extraocular motility was normal, as was the remainder of the examination. The dose of subcutaneous methotrexate was increased, and the dose of prednisone was increased to 20 mg per day. During the next 6 weeks, the pain in the left eye persisted, and periorbital swelling and proptosis developed on the left side. The dose of prednisone was increased to 40 mg per day, without improvement, and then to 60 mg per day. During this time, cellulitis of the right lower abdominal wall developed. A course of oral doxycycline was administered, followed by a course of oral cephalexin and topical mupirocin; methotrexate was discontinued. Eight weeks before this evaluation, the proptosis persisted. Mycophenolate mofetil was prescribed, and the dose of prednisone was decreased to 40 mg per day. The patient was referred to a rheumatologist and ophthalmologist at this hospital for further evaluation.
On evaluation in the ophthalmology and rheumatology clinics at this hospital, the patient reported proptosis and a 2-week history of diplopia in all directions of gaze, without pain. He had seasonal allergic rhinitis and a remote history of esotropia, asthma, tonsillectomy, adenoidectomy, and myringotomy. Nine months earlier, he had had an episode of bilateral submandibular sialadenitis; a test for mumps virus infection had been negative. Medications included prednisone, mycophenolate mofetil, cholecalciferol, and Saccharomyces boulardii. Ibuprofen had caused itching. The patient was a college student and lived in the southern central United States. He did not drink alcohol, smoke tobacco, or use illicit drugs. His grandmother had Graves' disease.
On examination, the patient had a cushingoid appearance. He had exotropia and minimal proptosis of the left eye, pallor of the right optic disk, and a right inferior central defect on visual-field testing. Examination of the skin revealed striae and acne (Figure 1). The remainder of the examination was normal. Laboratory test results are shown in Table 1. Urinalysis was normal; the urine protein level was 15.7 mg per deciliter (reference range, 0.0 to 13.5), and the urine protein:creatinine ratio was 0.05 (reference range, <0.15). Imaging studies were obtained.	
Figure 1 
Dr. Katherine L. Reinshagen: MRI of the orbits was performed (Figure 2). Contrast-enhanced T1-weighted images, obtained with and without fat suppression, showed abnormal fusiform enlargement and increased enhancement of the left medial and inferior rectus muscles, with a central area of hypoenhancement of the left medial rectus muscle. There was relative sparing of the musculotendinous insertions and no substantial surrounding fat stranding. In addition, T2-weighted images showed hyperintense signal in the left medial and inferior rectus muscles, a finding suggestive of edema. There was mild proptosis of the left globe. The right orbit and paranasal sinuses were essentially unremarkable.	
Figure 2 
Dr. Matza: A diagnostic procedure was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of eye pain, periorbital swelling, proptosis, and diplopia, along with the MRI findings of abnormal fusiform enlargement and increased enhancement of the left medial and inferior rectus muscles, are indicative of an inflammatory condition affecting the eye muscles, specifically the extraocular muscles. The patient's symptoms improved with corticosteroid treatment, which is typically used to reduce inflammation, further supporting an inflammatory condition. The patient's lack of response to antibiotics and the absence of infectious symptoms suggest that the condition is not infectious in nature. The patient's normal thyroid hormone levels rule out thyroid eye disease, a common cause of eye muscle inflammation. The recurrent nature of the patient's symptoms and the involvement of both eyes, albeit at different times, suggest a systemic condition. Given these findings, the most likely diagnosis is idiopathic orbital inflammatory syndrome, also known as orbital pseudotumor.\n\nDiagnosis: Idiopathic Orbital Inflammatory Syndrome (Orbital Pseudotumor)""
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        ""content"": ""The patient's symptoms of eye pain, periorbital swelling, proptosis, and diplopia, along with the MRI findings of enlargement and increased enhancement of the extraocular muscles, are suggestive of an inflammatory condition affecting the orbit. The fact that the symptoms responded to corticosteroids but recurred when the dose was decreased, and the absence of thyroid dysfunction, make thyroid eye disease less likely. The recurrent nature of the symptoms, the involvement of different muscles at different times, and the lack of other systemic symptoms make a systemic vasculitis or sarcoidosis less likely. The MRI findings of muscle enlargement with central areas of hypoenhancement and hyperintense signal on T2-weighted images are suggestive of edema and inflammation within the muscles, which is characteristic of idiopathic orbital inflammatory syndrome (IOIS), also known as orbital pseudotumor. \n\nDiagnosis: Idiopathic Orbital Inflammatory Syndrome (Orbital Pseudotumor)""
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        ""content"": ""The patient is an 18-year-old male presenting with diplopia and proptosis of the left eye. He has a history of similar symptoms in the right eye, which responded to treatment with prednisone and methotrexate. The differential diagnosis for this patient includes Graves' disease, orbital pseudotumor, orbital cellulitis, and lymphoma. Graves' disease is less likely given the patient's normal thyrotropin and free thyroxine levels. Orbital cellulitis is also less likely given the lack of infection signs and the patient's response to immunosuppressive therapy. Lymphoma could present with similar symptoms, but the patient's young age and lack of systemic symptoms make this less likely. The most likely diagnosis is orbital pseudotumor, also known as idiopathic orbital inflammation. This condition is characterized by inflammation of the eye muscles and can cause proptosis, diplopia, and pain. It often responds to corticosteroid treatment, as seen in this patient. \n\nDiagnosis: Orbital pseudotumor (idiopathic orbital inflammation)""
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10.1056/NEJMcpc1810386,Case 38-2018: A 54-Year-Old Man with New Heart Failure,"Hemoglobin (g/dl)   16.3   15.7
Hematocrit (%) 38.0–50.0 47.9   47.0
White-cell count (per mm3
) 400 ,000 8600   8040
Platelet count (per mm3
) 135,00 0,000 244,000   220,000
Sodium (mmol/liter)  134   135
Potassium (mmol/liter)  4.9   4.1
Chloride (mmol/liter)  96   98
Carbon dioxide (mmol/liter) 2 1 21   23
Urea nitrogen (mg/dl)  16   16
Creatinine (mg/dl) 0.86   0.89
Glucose (mg/dl) 74–106 103   114
Albumin (g/dl) 3.5–4.8 4.1   3.4
Troponin T (ng/ml) <0.03   <0.03  
N-terminal pro–B-type natriuretic 
peptide (pg/ml) 21,332  23,774
Alanine aminotransferase (U/liter) 87   76
Aspartate aminotransferase (U/liter)  34   32
Alkaline phosphatase (U/liter) 66   66
Total bilirubin (mg/dl)  3.9  3.5
Direct bilirubin (mg/dl) 0.  1.0
Lactate (mmol/liter)   1.2
Venous blood pH   7.43
Erythrocyte sedimentation rate (mm/hr)   2
Antinuclear antibody Negative at 1:80 
and 1:160
Positive at 1:40, 
speckled pattern
Antitreponemal antibody Negative Negative",Heart failure due to aortic insufficiency and thoracic aortic aneurysm,"Dilated cardiomyopathy due to chronic severe aortic regurgitation, resulting from aortic dilatation.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 54-year-old man was evaluated at this hospital because of new heart failure.
One month before this evaluation, a nonproductive cough developed after the patient took a business trip to Tennessee. During the next week, the cough became productive of intermittent yellowish-brown sputum and was associated with fatigue and dyspnea. The patient thought he had bronchitis and stopped smoking. During the subsequent 3 weeks, he had progressive debilitating fatigue, anorexia, 10 kg of weight gain, difficulty sleeping while lying flat, and swelling in both legs.
The patient's dyspnea worsened, was provoked by any amount of exertion, and then started to occur at rest. He presented to the emergency department of another hospital. He could not sleep while lying flat owing to severe dyspnea; he had slept in a recliner for a few nights and had awakened several times with paroxysmal dyspnea. The temperature was 36.6[degrees]C, the heart rate 107 beats per minute, the blood pressure 155/73 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 96% while he was receiving oxygen through a nasal cannula at a rate of 2 liters per minute. Examination was notable for crackles in the lungs and edema in the legs. Levels of amylase and lipase were normal; other test results are shown in Table 1. An electrocardiogram showed sinus tachycardia at a rate of 101 beats per minute, first-degree atrioventricular delay, poor R-wave progression, left atrial enlargement, left ventricular hypertrophy, and nonspecific ST-T wave abnormalities that were most notable in the apical leads. Chest radiography was performed.	
Table 1 
Dr. Nandini M. Meyersohn: On posteroanterior and lateral radiographs of the chest (Figure 1), pulmonary vascular markings were increased in number and more prominent than typically seen, a finding suggestive of pulmonary edema, and there was a small left pleural effusion. The cardiac silhouette was markedly enlarged, which could represent cardiomegaly or pericardial effusion. The aorta appeared ectatic. There was no evidence of hilar lymphadenopathy.	
Figure 1 
Dr. Sarma: Furosemide was administered intravenously, and the patient was transferred to the emergency department of this hospital. During the initial evaluation at this hospital, he reported a history of untreated systemic hypertension. A review of systems was notable for the presence of occasional streaks of blood in the sputum during the previous weeks and dysgeusia; the patient had no fever, chills, night sweats, chest pain, chest pressure, palpitations, light-headedness, dizziness, leg pain, claudication, rash, or focal neurologic symptoms. He had received regular dental care. He took no medications and had no known allergies to medications. He lived alone and worked in sales. He had smoked six cigars daily for 30 years; he had stopped smoking 1 month earlier. He occasionally smoked marijuana and drank one or two beers or glasses of wine daily. His father had died of a myocardial infarction at 67 years of age.
On examination, the temperature was 36.4[degrees]C, the heart rate 102 beats per minute, the blood pressure 142/75 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 94% while the patient was receiving oxygen through a nasal cannula at a rate of 4 liters per minute. He was middle-aged and of normal stature, without dysmorphic features, and he appeared to be anxious, fatigued, diaphoretic, and in mild respiratory distress. His dentition was normal. The jugular venous pulse was elevated to 12 cm of water, and the carotid pulse was described as ""collapsing."" The point of maximum cardiac impulse was shifted laterally to the anterior axillary line. The heart rate was tachycardic; a decrescendo murmur (grade 2 of 4) was heard nearly throughout diastole and was most prominent at the right upper sternal border, and there was no S3 gallop. There were bibasilar lung crackles. The abdomen was mildly distended. The arms and legs had robust, symmetric pulses and were warm; there was symmetric 3+ leg edema to the midthighs. Examination of the fingernails revealed alternating reddening and blanching pallor that was synchronized with the heart rate. The stool was guaiac-negative. There was no rash or lymphadenopathy, and the remainder of the examination was normal.
Levels of calcium, magnesium, phosphorus, total protein, globulin, and glycated hemoglobin were normal; other test results are shown in Table 1. Findings on an electrocardiogram were similar to those seen on the previous tracing (Figure 1).
Additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 54-year-old man was evaluated at this hospital because of new heart failure.
One month before this evaluation, a nonproductive cough developed after the patient took a business trip to Tennessee. During the next week, the cough became productive of intermittent yellowish-brown sputum and was associated with fatigue and dyspnea. The patient thought he had bronchitis and stopped smoking. During the subsequent 3 weeks, he had progressive debilitating fatigue, anorexia, 10 kg of weight gain, difficulty sleeping while lying flat, and swelling in both legs.
The patient's dyspnea worsened, was provoked by any amount of exertion, and then started to occur at rest. He presented to the emergency department of another hospital. He could not sleep while lying flat owing to severe dyspnea; he had slept in a recliner for a few nights and had awakened several times with paroxysmal dyspnea. The temperature was 36.6[degrees]C, the heart rate 107 beats per minute, the blood pressure 155/73 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 96% while he was receiving oxygen through a nasal cannula at a rate of 2 liters per minute. Examination was notable for crackles in the lungs and edema in the legs. Levels of amylase and lipase were normal; other test results are shown in Table 1. An electrocardiogram showed sinus tachycardia at a rate of 101 beats per minute, first-degree atrioventricular delay, poor R-wave progression, left atrial enlargement, left ventricular hypertrophy, and nonspecific ST-T wave abnormalities that were most notable in the apical leads. Chest radiography was performed.	
Table 1 
Dr. Nandini M. Meyersohn: On posteroanterior and lateral radiographs of the chest (Figure 1), pulmonary vascular markings were increased in number and more prominent than typically seen, a finding suggestive of pulmonary edema, and there was a small left pleural effusion. The cardiac silhouette was markedly enlarged, which could represent cardiomegaly or pericardial effusion. The aorta appeared ectatic. There was no evidence of hilar lymphadenopathy.	
Figure 1 
Dr. Sarma: Furosemide was administered intravenously, and the patient was transferred to the emergency department of this hospital. During the initial evaluation at this hospital, he reported a history of untreated systemic hypertension. A review of systems was notable for the presence of occasional streaks of blood in the sputum during the previous weeks and dysgeusia; the patient had no fever, chills, night sweats, chest pain, chest pressure, palpitations, light-headedness, dizziness, leg pain, claudication, rash, or focal neurologic symptoms. He had received regular dental care. He took no medications and had no known allergies to medications. He lived alone and worked in sales. He had smoked six cigars daily for 30 years; he had stopped smoking 1 month earlier. He occasionally smoked marijuana and drank one or two beers or glasses of wine daily. His father had died of a myocardial infarction at 67 years of age.
On examination, the temperature was 36.4[degrees]C, the heart rate 102 beats per minute, the blood pressure 142/75 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 94% while the patient was receiving oxygen through a nasal cannula at a rate of 4 liters per minute. He was middle-aged and of normal stature, without dysmorphic features, and he appeared to be anxious, fatigued, diaphoretic, and in mild respiratory distress. His dentition was normal. The jugular venous pulse was elevated to 12 cm of water, and the carotid pulse was described as ""collapsing."" The point of maximum cardiac impulse was shifted laterally to the anterior axillary line. The heart rate was tachycardic; a decrescendo murmur (grade 2 of 4) was heard nearly throughout diastole and was most prominent at the right upper sternal border, and there was no S3 gallop. There were bibasilar lung crackles. The abdomen was mildly distended. The arms and legs had robust, symmetric pulses and were warm; there was symmetric 3+ leg edema to the midthighs. Examination of the fingernails revealed alternating reddening and blanching pallor that was synchronized with the heart rate. The stool was guaiac-negative. There was no rash or lymphadenopathy, and the remainder of the examination was normal.
Levels of calcium, magnesium, phosphorus, total protein, globulin, and glycated hemoglobin were normal; other test results are shown in Table 1. Findings on an electrocardiogram were similar to those seen on the previous tracing (Figure 1).
Additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of a productive cough, fatigue, dyspnea, weight gain, difficulty sleeping while lying flat, and swelling in both legs are indicative of heart failure. The patient's history of untreated systemic hypertension is a risk factor for heart failure. The physical examination findings of an elevated jugular venous pulse, a laterally shifted point of maximum cardiac impulse, bibasilar lung crackles, and leg edema further support the diagnosis of heart failure. The presence of a decrescendo murmur heard throughout diastole and most prominent at the right upper sternal border suggests aortic regurgitation, which can lead to heart failure. The chest radiograph findings of increased pulmonary vascular markings, a small left pleural effusion, and an enlarged cardiac silhouette are consistent with heart failure. The electrocardiogram findings of sinus tachycardia, first-degree atrioventricular delay, poor R-wave progression, left atrial enlargement, and left ventricular hypertrophy are also consistent with heart failure.\n\nDiagnosis: Heart failure due to aortic regurgitation.""
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        ""content"": ""The patient's symptoms of a nonproductive cough, fatigue, dyspnea, weight gain, difficulty sleeping while lying flat, and swelling in both legs are indicative of heart failure. The patient's history of untreated systemic hypertension is a risk factor for heart failure. The physical examination findings of an elevated jugular venous pulse, a laterally shifted point of maximum cardiac impulse, bibasilar lung crackles, and leg edema further support the diagnosis of heart failure. The presence of a decrescendo murmur heard nearly throughout diastole and most prominent at the right upper sternal border suggests aortic regurgitation, which can lead to heart failure. The chest radiograph findings of increased pulmonary vascular markings, a small left pleural effusion, and an enlarged cardiac silhouette are consistent with heart failure. The electrocardiogram findings of sinus tachycardia, first-degree atrioventricular delay, poor R-wave progression, left atrial enlargement, and left ventricular hypertrophy are also consistent with heart failure.\n\nDiagnosis: Heart failure due to aortic regurgitation.""
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        ""content"": ""The patient is a 54-year-old man presenting with new onset heart failure, productive cough, fatigue, anorexia, weight gain, orthopnea, paroxysmal nocturnal dyspnea, and bilateral leg edema. These symptoms are indicative of congestive heart failure. The patient also has a history of untreated systemic hypertension, which is a risk factor for heart failure. The differential diagnosis for this patient includes ischemic heart disease, hypertensive heart disease, valvular heart disease, and cardiomyopathy. The patient's father had a history of myocardial infarction, which increases the patient's risk for ischemic heart disease. However, the patient does not report any chest pain or pressure, which are typical symptoms of ischemic heart disease. The patient's history of untreated hypertension makes hypertensive heart disease a likely diagnosis. The patient's physical examination reveals a decrescendo murmur heard throughout diastole, which is suggestive of aortic regurgitation, a type of valvular heart disease. However, the patient does not report any symptoms of infective endocarditis, such as fever, chills, or night sweats. The patient's symptoms and physical examination findings are not suggestive of cardiomyopathy. Therefore, the most likely diagnosis is hypertensive heart disease leading to congestive heart failure.\n\nDiagnosis: Hypertensive heart disease leading to congestive heart failure.""
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10.1056/NEJMcpc1807501,Case 37-2018: A 23-Year-Old Woman with Vision Loss,,Susac’s syndrome.,Susac’s syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 23-year-old right-handed woman with a history of migraines was evaluated at this hospital for vertigo and vision loss affecting the right eye.
Six days before admission, a right frontal headache and right retro-orbital pain developed; these features had not been typical of the patient's previous migraines. Five days before admission, the patient awoke with an alteration in her vision, which she described as a ""gray dot"" approximately 6 cm in diameter (as measured with the use of an Amsler grid held at 12 inches) and was located in the inferonasal field of vision of the right eye. Later that day, she had intermittent diminished vision in the right eye, which she described as ""white appearing"" and lasting for 45 to 60 seconds at a time. The size of the abnormality was difficult for the patient to define, but the abnormality did not involve the entire field of vision of the right eye. She did not have pain with eye movement, floaters, scintillating scotomata, or fortification spectra. When she covered her right eye, the vision in her left eye was normal.
Three days before admission, several episodes of vertigo occurred. The patient described the vertigo as ""room spinning"" and lasting for approximately 30 seconds. The vertigo was not provoked by angular head movements. Intermittent nonpositional bifrontal headaches occurred one or two times daily, particularly when the patient was straining her eyes to look at a cellular telephone or computer. She did not have facial numbness, loss of vision with eye movement, or other neurologic symptoms. The abnormality that she had described as a gray dot in the inferonasal field of vision of the right eye remained fixed, and the night before admission, she went to a hospital that specializes in ophthalmology and is affiliated with this hospital.
In the emergency department of the affiliated hospital, the temperature was 36.6[degrees]C, the pulse 79 beats per minute, the blood pressure 103/64 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. Visual acuity was 20/20 in both eyes. On the Ishihara color test, six of eight color plates were identified correctly in the visual field of the right eye (two half plates were missed in the area of reported loss of vision) and eight of eight color plates were identified correctly in the visual field of the left eye. The pupils were equal, round, and reactive to light, without a relative afferent pupillary defect. Automated perimetry revealed a dense depression in the inferonasal field of vision of the right eye. Slit-lamp examination of the eyes revealed normal adnexa, lids, lashes, conjunctivae, and sclerae and clear corneas. The anterior chambers, irises, lenses, and vitreous were normal in both eyes. The intraocular pressure was 12 mm Hg in both eyes. The optic nerves were pink, with normal cups and sharp margins. There was an area of mild macular whitening superotemporal to the fovea in the right eye. The vessels appeared normal in both eyes, without emboli, Gass plaques, boxcarring (segmentation of blood in retinal arterioles), or sheathing. Extraocular movements were full bilaterally, without nystagmus.
The next morning, the patient was transferred to the emergency department of this hospital for further diagnostic evaluation. She reported stable visual-field defects and ongoing intermittent headaches. She had had no rash or ulcers. There was a 16-year history of migraines without aura; the migraines occurred every 1 to 3 months, were pulsatile in quality, were associated with sensitivity to light, and resolved with sleep. There was no history of blood clots, miscarriage, hypertension, hyperlipidemia, or autoimmune disease. The only medication was an etonogestrel implant. There were no known drug allergies. There was no family history of stroke, hypercoagulability, or cardiac disease. The patient worked in a nursing home and lived alone in eastern Massachusetts. She was sexually active with one male partner, with whom she was in a monogamous relationship. She drank alcohol occasionally and did not smoke tobacco or use illicit drugs.
The results of the ophthalmologic examination had not changed from the examination at the affiliated hospital, and the results of the general and neurologic examinations were normal. Blood levels of electrolytes, glucose, glycated hemoglobin, thyrotropin, C-reactive protein, and homocysteine were normal, as were results of renal- and liver-function tests, the prothrombin time, the international normalized ratio, the partial-thromboplastin time, the complete blood count, the differential count, and the erythrocyte sedimentation rate. Test results were normal for protein S, protein C, and antithrombin III activity, as well as the prothrombin G20210A mutation and activated protein C resistance. A lupus anticoagulant screen was negative. An assay for antinuclear antibodies was positive at 1:640 with a speckled pattern, and assays for antineutrophil cytoplasmic antibodies (ANCAs), [beta]2-glycoprotein 1 IgM and IgG antibodies, and anticardiolipin IgM and IgG antibodies were negative. A lumbar puncture revealed colorless cerebrospinal fluid, with an opening pressure of 13 cm of water, a glucose level of 62 mg per deciliter (3.4 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]), a total protein level of 77 mg per deciliter (reference range, 5 to 55), a total nucleated-cell count of 1 per cubic millimeter (reference range, 0 to 5), and a red-cell count of 3 per cubic millimeter (reference range, 0 to 5). Low-dose aspirin was administered, and the patient was admitted to the neurology service.
One day after admission, hearing loss and tinnitus of the right ear developed. Audiometry revealed bilateral sensorineural hearing loss that was more severe in the right ear than in the left ear, with normal tympanic-membrane mobility bilaterally. On the fourth day, color photographs of the fundus were obtained, and fluorescein angiography was performed to evaluate the retinal vasculature.
Dr. Lucy H. Young: Wide-field photographs of the fundus showed retinal whitening superotemporal to the fovea in the right eye (Figure 1A) and a subtle area of retinal whitening along the inferotemporal arcade of the left eye (Figure 1B). Fluorescein angiography revealed delayed filling of two arteriolar branches along the superotemporal arcade of the right eye, with one remaining blocked even at 39 seconds after the administration of fluorescein (Figure 2A). In the left eye, blocked arterioles were noted in the inferonasal and inferotemporal periphery (Figure 2B). Images obtained 5 minutes after the administration of fluorescein showed segmental perivascular staining in both eyes (Figure 2C and 2D).	
Figure 1 
Dr. Levin: An additional test was performed, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 23-year-old right-handed woman with a history of migraines was evaluated at this hospital for vertigo and vision loss affecting the right eye.
Six days before admission, a right frontal headache and right retro-orbital pain developed; these features had not been typical of the patient's previous migraines. Five days before admission, the patient awoke with an alteration in her vision, which she described as a ""gray dot"" approximately 6 cm in diameter (as measured with the use of an Amsler grid held at 12 inches) and was located in the inferonasal field of vision of the right eye. Later that day, she had intermittent diminished vision in the right eye, which she described as ""white appearing"" and lasting for 45 to 60 seconds at a time. The size of the abnormality was difficult for the patient to define, but the abnormality did not involve the entire field of vision of the right eye. She did not have pain with eye movement, floaters, scintillating scotomata, or fortification spectra. When she covered her right eye, the vision in her left eye was normal.
Three days before admission, several episodes of vertigo occurred. The patient described the vertigo as ""room spinning"" and lasting for approximately 30 seconds. The vertigo was not provoked by angular head movements. Intermittent nonpositional bifrontal headaches occurred one or two times daily, particularly when the patient was straining her eyes to look at a cellular telephone or computer. She did not have facial numbness, loss of vision with eye movement, or other neurologic symptoms. The abnormality that she had described as a gray dot in the inferonasal field of vision of the right eye remained fixed, and the night before admission, she went to a hospital that specializes in ophthalmology and is affiliated with this hospital.
In the emergency department of the affiliated hospital, the temperature was 36.6[degrees]C, the pulse 79 beats per minute, the blood pressure 103/64 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. Visual acuity was 20/20 in both eyes. On the Ishihara color test, six of eight color plates were identified correctly in the visual field of the right eye (two half plates were missed in the area of reported loss of vision) and eight of eight color plates were identified correctly in the visual field of the left eye. The pupils were equal, round, and reactive to light, without a relative afferent pupillary defect. Automated perimetry revealed a dense depression in the inferonasal field of vision of the right eye. Slit-lamp examination of the eyes revealed normal adnexa, lids, lashes, conjunctivae, and sclerae and clear corneas. The anterior chambers, irises, lenses, and vitreous were normal in both eyes. The intraocular pressure was 12 mm Hg in both eyes. The optic nerves were pink, with normal cups and sharp margins. There was an area of mild macular whitening superotemporal to the fovea in the right eye. The vessels appeared normal in both eyes, without emboli, Gass plaques, boxcarring (segmentation of blood in retinal arterioles), or sheathing. Extraocular movements were full bilaterally, without nystagmus.
The next morning, the patient was transferred to the emergency department of this hospital for further diagnostic evaluation. She reported stable visual-field defects and ongoing intermittent headaches. She had had no rash or ulcers. There was a 16-year history of migraines without aura; the migraines occurred every 1 to 3 months, were pulsatile in quality, were associated with sensitivity to light, and resolved with sleep. There was no history of blood clots, miscarriage, hypertension, hyperlipidemia, or autoimmune disease. The only medication was an etonogestrel implant. There were no known drug allergies. There was no family history of stroke, hypercoagulability, or cardiac disease. The patient worked in a nursing home and lived alone in eastern Massachusetts. She was sexually active with one male partner, with whom she was in a monogamous relationship. She drank alcohol occasionally and did not smoke tobacco or use illicit drugs.
The results of the ophthalmologic examination had not changed from the examination at the affiliated hospital, and the results of the general and neurologic examinations were normal. Blood levels of electrolytes, glucose, glycated hemoglobin, thyrotropin, C-reactive protein, and homocysteine were normal, as were results of renal- and liver-function tests, the prothrombin time, the international normalized ratio, the partial-thromboplastin time, the complete blood count, the differential count, and the erythrocyte sedimentation rate. Test results were normal for protein S, protein C, and antithrombin III activity, as well as the prothrombin G20210A mutation and activated protein C resistance. A lupus anticoagulant screen was negative. An assay for antinuclear antibodies was positive at 1:640 with a speckled pattern, and assays for antineutrophil cytoplasmic antibodies (ANCAs), [beta]2-glycoprotein 1 IgM and IgG antibodies, and anticardiolipin IgM and IgG antibodies were negative. A lumbar puncture revealed colorless cerebrospinal fluid, with an opening pressure of 13 cm of water, a glucose level of 62 mg per deciliter (3.4 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]), a total protein level of 77 mg per deciliter (reference range, 5 to 55), a total nucleated-cell count of 1 per cubic millimeter (reference range, 0 to 5), and a red-cell count of 3 per cubic millimeter (reference range, 0 to 5). Low-dose aspirin was administered, and the patient was admitted to the neurology service.
One day after admission, hearing loss and tinnitus of the right ear developed. Audiometry revealed bilateral sensorineural hearing loss that was more severe in the right ear than in the left ear, with normal tympanic-membrane mobility bilaterally. On the fourth day, color photographs of the fundus were obtained, and fluorescein angiography was performed to evaluate the retinal vasculature.
Dr. Lucy H. Young: Wide-field photographs of the fundus showed retinal whitening superotemporal to the fovea in the right eye (Figure 1A) and a subtle area of retinal whitening along the inferotemporal arcade of the left eye (Figure 1B). Fluorescein angiography revealed delayed filling of two arteriolar branches along the superotemporal arcade of the right eye, with one remaining blocked even at 39 seconds after the administration of fluorescein (Figure 2A). In the left eye, blocked arterioles were noted in the inferonasal and inferotemporal periphery (Figure 2B). Images obtained 5 minutes after the administration of fluorescein showed segmental perivascular staining in both eyes (Figure 2C and 2D).	
Figure 1 
Dr. Levin: An additional test was performed, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Susac's Syndrome. The patient's symptoms of vision loss, vertigo, and hearing loss are consistent with Susac's Syndrome, a rare disorder characterized by the triad of encephalopathy, branch retinal artery occlusion, and hearing loss. The patient's ophthalmologic examination revealed retinal whitening and blocked arterioles, which are indicative of branch retinal artery occlusion. The patient's audiometry test revealed sensorineural hearing loss, another key feature of Susac's Syndrome. The patient's vertigo and headaches could be indicative of encephalopathy, the third component of the triad. The patient's age and sex are also consistent with the typical demographic for Susac's Syndrome, which most commonly affects young women.""
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        ""content"": ""The patient is a young woman with a history of migraines who presents with new onset vertigo, vision loss in the right eye, and hearing loss and tinnitus in the right ear. The differential diagnosis for this patient includes multiple sclerosis, Susac syndrome, and migrainous infarction. Multiple sclerosis is less likely given the absence of other neurologic symptoms and the lack of lesions on MRI. Migrainous infarction is also less likely given the absence of a prolonged migrainous aura and the presence of hearing loss, which is not typically associated with this condition. The constellation of encephalopathy (manifested as headache and vertigo), branch retinal artery occlusions, and sensorineural hearing loss is characteristic of Susac syndrome. This is further supported by the findings of retinal whitening and blocked arterioles on fluorescein angiography, which are indicative of retinal vasculitis, a key feature of Susac syndrome.\n\nDiagnosis: Susac syndrome.""
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10.1056/NEJMcpc1802832,Case 36-2018: A 29-Year-Old Man with an Incidentally Discovered Renal Mass,"Hemoglobin (g/dl)   14.3   14.3
Hematocrit (%) 42–52 44   43.1
White-cell count (per mm3
)   6400   6940
Platelet count (per mm3
)   209,000   220,000
Sodium (mmol/liter)   140   143
Potassium (mmol/liter)  3.7   4.1
Chloride (mmol/liter)  100   103
Carbon dioxide (mmol/liter) 27   25
Urea nitrogen (mg/dl)  10   12
Creatinine (mg/dl)  0.82   0.82
Glucose (mg/dl)  97   97
Calcium (mg/dl) 8.4–10.2 9.4   9.4
Albumin (g/dl)  4.6   4.9
Glycated hemoglobin (%)  5.9 
Prothrombin time (sec) 14.2
Prothrombin-time international 
normalized ratio
  1.2
Partial-thromboplastin time (sec) 22. 5.0 25.6
Urine
Specific gravity 1.015–1.025 1.025   1.020
pH 5. .0 5.5   5.5
Red cells Negative Negative Negative Negative
White cells Negative Negative Negative Negative
Nitrite Negative Negative Negative Negative
Protein Negative Negative Negative Negative",The t(6;11) TFEB translocation variant of renalcell carcinoma,Renal-cell carcinoma.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-year-old man was seen at this hospital because of an incidentally discovered renal mass.
The patient had been well until 6 weeks before this evaluation, when he identified a painless lump above his left testicle during a monthly self-examination. He was evaluated at his primary care physician's office at another hospital. Examination confirmed a soft, nontender mass, which was described as ""boggy,"" on the superior aspect of the left testicle, without associated erythema. Laboratory test results (Table 1) and imaging studies of the testes and scrotum were obtained.	
Table 1 
Dr. Joseph F. Simeone: Ultrasonography of the scrotum and testes (Figure 1) revealed normal testes, a varicocele on the left side, and a cyst (0.6 cm in diameter) on the right side of the epididymal head. There was an incidental mixed solid and cystic mass (11.8 cm by 10.8 cm by 9.4 cm) arising from the lower aspect of the right kidney. The left kidney was normal.	
Figure 1 
Computed tomography (CT) of the abdomen and pelvis (Figure 2), performed after the intravenous administration of contrast material, confirmed the presence of a mixed solid and cystic mass (11 cm in diameter) at the lower pole of the right kidney. Thin mural calcification was noted. There was no evidence of hydronephrosis, venous invasion, enlarged lymph nodes, liver or pancreatic lesions, or adrenal nodules. The mass displaced the inferior vena cava to the left.	
Figure 2 
Dr. Salari: The patient was referred to the urology clinic of this hospital. On evaluation, he reported mild discomfort in the right flank and right upper quadrant, along with a small bulge in that area. A review of systems was notable for the left scrotal mass and seasonal allergies. He had no fever, night sweats, weight loss, anorexia, fatigue, lymphadenopathy, pruritus, hematuria, dysuria, or pelvic or back pain. Medications included cetirizine, as needed, for seasonal allergic rhinitis. He had no known allergies to medications.
The patient worked as a cook. He had emigrated from South America 11 years before the current evaluation, and he lived in coastal Massachusetts. He had no recent history of travel. He was married and had a healthy 2-year-old son, and his wife was expecting another child. He did not smoke tobacco, drink alcohol, or use any illicit substances. His mother had had gastrointestinal stromal tumor, his father had had skin melanoma and had died of a stroke, and his maternal grandfather had died of gastric cancer. There was no family history of genitourinary cancer, renal disease, or genitourinary disease.
On examination, the heart rate was 70 beats per minute, and the blood pressure 127/81 mm Hg. The patient appeared to be well. There was a palpable nontender mass in the right abdomen, inferior to the liver. The genitourinary examination was notable for a varicocele on the left side; the varicocele was grade 2 of 3, indicating that it was palpable without a Valsalva maneuver. The phallus, scrotum, and testes were otherwise normal. The remainder of the examination was normal.
Blood levels of total protein, globulin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase were normal; other laboratory test results are shown in Table 1. CT of the chest revealed an intrapulmonary lymph node, but there was no evidence of pulmonary nodules or lymphadenopathy, findings that would suggest metastatic cancer.
Diagnostic and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 29-year-old man was seen at this hospital because of an incidentally discovered renal mass.
The patient had been well until 6 weeks before this evaluation, when he identified a painless lump above his left testicle during a monthly self-examination. He was evaluated at his primary care physician's office at another hospital. Examination confirmed a soft, nontender mass, which was described as ""boggy,"" on the superior aspect of the left testicle, without associated erythema. Laboratory test results (Table 1) and imaging studies of the testes and scrotum were obtained.	
Table 1 
Dr. Joseph F. Simeone: Ultrasonography of the scrotum and testes (Figure 1) revealed normal testes, a varicocele on the left side, and a cyst (0.6 cm in diameter) on the right side of the epididymal head. There was an incidental mixed solid and cystic mass (11.8 cm by 10.8 cm by 9.4 cm) arising from the lower aspect of the right kidney. The left kidney was normal.	
Figure 1 
Computed tomography (CT) of the abdomen and pelvis (Figure 2), performed after the intravenous administration of contrast material, confirmed the presence of a mixed solid and cystic mass (11 cm in diameter) at the lower pole of the right kidney. Thin mural calcification was noted. There was no evidence of hydronephrosis, venous invasion, enlarged lymph nodes, liver or pancreatic lesions, or adrenal nodules. The mass displaced the inferior vena cava to the left.	
Figure 2 
Dr. Salari: The patient was referred to the urology clinic of this hospital. On evaluation, he reported mild discomfort in the right flank and right upper quadrant, along with a small bulge in that area. A review of systems was notable for the left scrotal mass and seasonal allergies. He had no fever, night sweats, weight loss, anorexia, fatigue, lymphadenopathy, pruritus, hematuria, dysuria, or pelvic or back pain. Medications included cetirizine, as needed, for seasonal allergic rhinitis. He had no known allergies to medications.
The patient worked as a cook. He had emigrated from South America 11 years before the current evaluation, and he lived in coastal Massachusetts. He had no recent history of travel. He was married and had a healthy 2-year-old son, and his wife was expecting another child. He did not smoke tobacco, drink alcohol, or use any illicit substances. His mother had had gastrointestinal stromal tumor, his father had had skin melanoma and had died of a stroke, and his maternal grandfather had died of gastric cancer. There was no family history of genitourinary cancer, renal disease, or genitourinary disease.
On examination, the heart rate was 70 beats per minute, and the blood pressure 127/81 mm Hg. The patient appeared to be well. There was a palpable nontender mass in the right abdomen, inferior to the liver. The genitourinary examination was notable for a varicocele on the left side; the varicocele was grade 2 of 3, indicating that it was palpable without a Valsalva maneuver. The phallus, scrotum, and testes were otherwise normal. The remainder of the examination was normal.
Blood levels of total protein, globulin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase were normal; other laboratory test results are shown in Table 1. CT of the chest revealed an intrapulmonary lymph node, but there was no evidence of pulmonary nodules or lymphadenopathy, findings that would suggest metastatic cancer.
Diagnostic and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with a painless lump above his left testicle, which was confirmed to be a soft, nontender mass. However, the ultrasound and CT scan revealed a mixed solid and cystic mass in the lower aspect of the right kidney. The patient also reported mild discomfort in the right flank and right upper quadrant. The mass was also palpable in the right abdomen. The patient's family history includes gastrointestinal stromal tumor, skin melanoma, and gastric cancer, but no genitourinary cancer, renal disease, or genitourinary disease. The CT scan of the chest did not show any evidence of metastatic cancer. Given the imaging findings and the patient's symptoms, the most likely diagnosis is renal cell carcinoma.""
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        ""content"": ""The patient is a 29-year-old male who presents with a painless lump above his left testicle and a palpable nontender mass in the right abdomen. The differential diagnosis for this patient includes testicular cancer, renal cell carcinoma, and benign renal cyst. The patient's testicular lump was confirmed to be a varicocele and a cyst on the right side of the epididymal head, ruling out testicular cancer. The abdominal mass was confirmed to be a mixed solid and cystic mass arising from the lower aspect of the right kidney. The mass was not associated with hydronephrosis, venous invasion, enlarged lymph nodes, liver or pancreatic lesions, or adrenal nodules, which are common features of renal cell carcinoma. However, the presence of thin mural calcification and the size of the mass (11 cm in diameter) are more suggestive of a malignant process than a benign renal cyst. The patient's family history of gastrointestinal stromal tumor, skin melanoma, and gastric cancer also increases his risk for malignancy. \n\nDiagnosis: Renal cell carcinoma.""
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10.1056/NEJMcpc1616400,Case 35-2018: A 68-Year-Old Woman with Back Pain and a Remote History of Breast Cancer,"Hemoglobin (g/dl)   9.9
Hematocrit (%)   30.3
White-cell count (per mm3)   5030
Differential count (%)
Polymorphonuclear cells   58.8
Lymphocytes   30.8
Monocytes   5.9
Eosinophils   3.2
Basophils   1.1
Platelet count (per mm3
)   167
International normalized ratio   2.4","Hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer of the lobular type, with ESR1 mutations.",Primary breast carcinoma of the lobular type with metastasis to the bone (sacrum).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old woman with a history of bilateral breast cancer was evaluated at the oncology clinic of this hospital for back and pelvic pain.
Twenty-five years before the current evaluation, the patient was noted to have a small lump in her left breast during a routine gynecologic examination. A mammogram showed no abnormality. A biopsy of the breast mass was performed, and examination of the biopsy specimen revealed evidence of invasive carcinoma that was estrogen receptor (ER)-positive and progesterone receptor (PR)-positive. Partial mastectomy of the left breast and dissection of axillary lymph nodes were performed, and examination of the specimens revealed the presence of two separate and distinct primary tumors. Histopathological analysis revealed ER-positive invasive ductal carcinoma (first primary tumor, 3 cm in diameter) and invasive lobular carcinoma (second primary tumor, 3 cm in diameter). Of the 10 dissected axillary lymph nodes, 2 were positive for carcinoma. A bone scan and chest radiograph did not show evidence of metastatic disease, and blood electrolyte levels and results of liver- and renal-function tests were normal.
The patient participated in a clinical trial,1 in which she was randomly assigned to receive initial treatment with four cycles of cyclophosphamide, doxorubicin, methotrexate, and fluorouracil followed by radiation therapy of the breast. In accordance with the clinical trial protocol, she did not receive tamoxifen but was monitored regularly with active surveillance.
Twelve years after the initial diagnosis (13 years before the current evaluation), routine surveillance mammography revealed a cluster of calcifications in the right breast. An excisional biopsy was performed, and examination of the biopsy specimen revealed evidence of ductal carcinoma in situ and lobular neoplasia, with positive margins. The tumor was 1.2 cm in diameter, ER-positive, and moderately differentiated (grade 2 of 3). Genetic testing for a BRCA mutation was negative. The patient underwent partial mastectomy of the right breast followed by adjuvant radiation therapy, with a plan to complete 5 years of adjuvant anastrozole therapy.
Four years later (9 years before this evaluation), the patient had exertional dyspnea for 3 weeks. A ventilation-perfusion scan showed that there was a high probability of pulmonary embolism, and a D-dimer test was positive; the patient received a diagnosis of pulmonary embolism. Lupus anticoagulant was detected, although testing for cardiolipin IgG and IgM antibodies was negative. The patient was treated with low-molecular-weight heparin followed by warfarin therapy. During that time, she lost 22.7 kg, and anastrozole therapy was discontinued. Eighteen months after anastrozole was discontinued (7.5 years before this evaluation), pulmonary embolism recurred bilaterally, and the patient was again treated with warfarin therapy. Eight months before the current evaluation, pleuritic chest pain and axillary pain developed, and recurrent pulmonary embolism was again suspected.
Dr. Meline D. Hovnanian: Computed tomography (CT), performed according to a pulmonary embolism protocol, revealed that the pulmonary emboli had resolved. In addition, CT incidentally revealed enlargement of a left axillary lymph node (11 mm in the short axis) and of a left subpectoral lymph node (9 mm in the short axis) (Figure 1). Repeat mammography and breast ultrasonography were performed and revealed an enlarged left axillary lymph node (13 mm by 11 mm) that corresponded to one of the nodes seen on chest CT.	
Figure 1 
Ms. Doyle: Given the depth of the lymph node, biopsy with ultrasonographic guidance was considered to be too technically difficult to perform, particularly since the patient was receiving warfarin therapy and had an increased risk of bleeding. After the patient's surgical oncologist was consulted, a plan for short-term surveillance with imaging studies was implemented.
Dr. Hovnanian: Two months before this evaluation, repeat imaging studies, including chest CT, mammography, and breast ultrasonography, were performed. Findings on ultrasonography and mammography had not changed from the studies obtained 6 months earlier. However, chest CT revealed multiple mixed lytic and blastic lesions in the thoracic vertebrae, ribs, and sternum that had not been present on the previous study, along with a mild compression deformity in the thoracic spine with an extradural enhancing focus at T10. The left axillary and subpectoral lymph nodes had not changed. There were multiple enhancing lesions in the spleen that measured up to 12 mm in diameter. A focal hypodensity (12 mm in diameter) was present in the left lobe of the liver but could not be further characterized. A follow-up whole-body bone scan with technetium revealed multiple sites of increased uptake throughout the axial and appendicular skeleton (Figure 2).	
Figure 2 
Ms. Doyle: The patient was referred to the medical oncology clinic of this hospital for additional treatment. On presentation, she reported axial back pain. She mentioned that the pain had been present for several months and she thought it was related to a fall. She described the pain as sharp and stabbing with a burning quality, and she rated the pain in the midback region as 7 on a scale of 0 to 10 (with 10 indicating the most severe pain), noting that it was greater on the left side than on the right side. The pain was worse while she was sitting and was somewhat controlled with celecoxib. She did not report focal weakness, paresthesia, or a change in bowel habits.
Additional medical history was notable for fibroadenoma of the right breast, obesity, sleep apnea, hyperlipidemia, hypertension, osteoporosis, and a hydatidiform mole that had been treated with dilatation and curettage. Medications included warfarin, atenolol, hydrochlorothiazide-triamterene, pravastatin, sertraline, and as needed, celecoxib. Penicillin had caused a rash.
The patient worked in health care at a local hospital. She had smoked 1 pack of cigarettes daily for 25 years and had quit smoking 15 years before the current presentation. She was married and had one adult daughter. Her family history was notable for breast cancer in multiple relatives, including her mother at 70 years of age, a sister at 57 years of age, and a maternal aunt at 65 years of age. Her father had had prostate cancer and a stroke.
On examination, the temperature was 36.6[degrees]C, the heart rate 66 beats per minute, the blood pressure 120/80 mm Hg, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 40.9. On examination of the breasts and axillae, no lumps or lymph nodes were palpable; surgical sites and scars were well healed. There was mild focal tenderness of the spine just to the left of T10. The remainder of the examination was normal. Laboratory test results are shown in Table 1.	
Table 1 
Further diagnostic studies were performed, and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 68-year-old woman with a history of bilateral breast cancer was evaluated at the oncology clinic of this hospital for back and pelvic pain.
Twenty-five years before the current evaluation, the patient was noted to have a small lump in her left breast during a routine gynecologic examination. A mammogram showed no abnormality. A biopsy of the breast mass was performed, and examination of the biopsy specimen revealed evidence of invasive carcinoma that was estrogen receptor (ER)-positive and progesterone receptor (PR)-positive. Partial mastectomy of the left breast and dissection of axillary lymph nodes were performed, and examination of the specimens revealed the presence of two separate and distinct primary tumors. Histopathological analysis revealed ER-positive invasive ductal carcinoma (first primary tumor, 3 cm in diameter) and invasive lobular carcinoma (second primary tumor, 3 cm in diameter). Of the 10 dissected axillary lymph nodes, 2 were positive for carcinoma. A bone scan and chest radiograph did not show evidence of metastatic disease, and blood electrolyte levels and results of liver- and renal-function tests were normal.
The patient participated in a clinical trial,1 in which she was randomly assigned to receive initial treatment with four cycles of cyclophosphamide, doxorubicin, methotrexate, and fluorouracil followed by radiation therapy of the breast. In accordance with the clinical trial protocol, she did not receive tamoxifen but was monitored regularly with active surveillance.
Twelve years after the initial diagnosis (13 years before the current evaluation), routine surveillance mammography revealed a cluster of calcifications in the right breast. An excisional biopsy was performed, and examination of the biopsy specimen revealed evidence of ductal carcinoma in situ and lobular neoplasia, with positive margins. The tumor was 1.2 cm in diameter, ER-positive, and moderately differentiated (grade 2 of 3). Genetic testing for a BRCA mutation was negative. The patient underwent partial mastectomy of the right breast followed by adjuvant radiation therapy, with a plan to complete 5 years of adjuvant anastrozole therapy.
Four years later (9 years before this evaluation), the patient had exertional dyspnea for 3 weeks. A ventilation-perfusion scan showed that there was a high probability of pulmonary embolism, and a D-dimer test was positive; the patient received a diagnosis of pulmonary embolism. Lupus anticoagulant was detected, although testing for cardiolipin IgG and IgM antibodies was negative. The patient was treated with low-molecular-weight heparin followed by warfarin therapy. During that time, she lost 22.7 kg, and anastrozole therapy was discontinued. Eighteen months after anastrozole was discontinued (7.5 years before this evaluation), pulmonary embolism recurred bilaterally, and the patient was again treated with warfarin therapy. Eight months before the current evaluation, pleuritic chest pain and axillary pain developed, and recurrent pulmonary embolism was again suspected.
Dr. Meline D. Hovnanian: Computed tomography (CT), performed according to a pulmonary embolism protocol, revealed that the pulmonary emboli had resolved. In addition, CT incidentally revealed enlargement of a left axillary lymph node (11 mm in the short axis) and of a left subpectoral lymph node (9 mm in the short axis) (Figure 1). Repeat mammography and breast ultrasonography were performed and revealed an enlarged left axillary lymph node (13 mm by 11 mm) that corresponded to one of the nodes seen on chest CT.	
Figure 1 
Ms. Doyle: Given the depth of the lymph node, biopsy with ultrasonographic guidance was considered to be too technically difficult to perform, particularly since the patient was receiving warfarin therapy and had an increased risk of bleeding. After the patient's surgical oncologist was consulted, a plan for short-term surveillance with imaging studies was implemented.
Dr. Hovnanian: Two months before this evaluation, repeat imaging studies, including chest CT, mammography, and breast ultrasonography, were performed. Findings on ultrasonography and mammography had not changed from the studies obtained 6 months earlier. However, chest CT revealed multiple mixed lytic and blastic lesions in the thoracic vertebrae, ribs, and sternum that had not been present on the previous study, along with a mild compression deformity in the thoracic spine with an extradural enhancing focus at T10. The left axillary and subpectoral lymph nodes had not changed. There were multiple enhancing lesions in the spleen that measured up to 12 mm in diameter. A focal hypodensity (12 mm in diameter) was present in the left lobe of the liver but could not be further characterized. A follow-up whole-body bone scan with technetium revealed multiple sites of increased uptake throughout the axial and appendicular skeleton (Figure 2).	
Figure 2 
Ms. Doyle: The patient was referred to the medical oncology clinic of this hospital for additional treatment. On presentation, she reported axial back pain. She mentioned that the pain had been present for several months and she thought it was related to a fall. She described the pain as sharp and stabbing with a burning quality, and she rated the pain in the midback region as 7 on a scale of 0 to 10 (with 10 indicating the most severe pain), noting that it was greater on the left side than on the right side. The pain was worse while she was sitting and was somewhat controlled with celecoxib. She did not report focal weakness, paresthesia, or a change in bowel habits.
Additional medical history was notable for fibroadenoma of the right breast, obesity, sleep apnea, hyperlipidemia, hypertension, osteoporosis, and a hydatidiform mole that had been treated with dilatation and curettage. Medications included warfarin, atenolol, hydrochlorothiazide-triamterene, pravastatin, sertraline, and as needed, celecoxib. Penicillin had caused a rash.
The patient worked in health care at a local hospital. She had smoked 1 pack of cigarettes daily for 25 years and had quit smoking 15 years before the current presentation. She was married and had one adult daughter. Her family history was notable for breast cancer in multiple relatives, including her mother at 70 years of age, a sister at 57 years of age, and a maternal aunt at 65 years of age. Her father had had prostate cancer and a stroke.
On examination, the temperature was 36.6[degrees]C, the heart rate 66 beats per minute, the blood pressure 120/80 mm Hg, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 40.9. On examination of the breasts and axillae, no lumps or lymph nodes were palpable; surgical sites and scars were well healed. There was mild focal tenderness of the spine just to the left of T10. The remainder of the examination was normal. Laboratory test results are shown in Table 1.	
Table 1 
Further diagnostic studies were performed, and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""This is a 68-year-old woman with a history of bilateral breast cancer who presents with back and pelvic pain. She has a history of ER-positive invasive ductal carcinoma and invasive lobular carcinoma in the left breast, and ductal carcinoma in situ and lobular neoplasia in the right breast. She also has a history of recurrent pulmonary embolism. Her current symptoms and imaging findings of multiple mixed lytic and blastic lesions in the thoracic vertebrae, ribs, and sternum, along with a mild compression deformity in the thoracic spine with an extradural enhancing focus at T10, are concerning for metastatic disease. The differential diagnosis includes metastatic breast cancer, primary bone cancer, and multiple myeloma. Primary bone cancer is less likely given her history of breast cancer and the presence of multiple lesions. Multiple myeloma typically presents with lytic lesions, hypercalcemia, renal disease, anemia, and bone pain, but this patient's laboratory results do not show hypercalcemia, renal disease, or anemia. Given her history of breast cancer and the presence of both lytic and blastic lesions, metastatic breast cancer is the most likely diagnosis.\n\nDiagnosis: Metastatic breast cancer.""
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10.1056/NEJMcpc1810387,Case 34-2018: A 58-Year-Old Woman with Paresthesia and Weakness of the Left Foot and Abdominal Wall,,Lyme meningoradiculitis,Lyme meningoradiculitis in the context of early disseminated Lyme disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 58-year-old woman was seen in the outpatient neurology clinic of this hospital in early autumn because of hypoesthesia, paresthesia, and weakness.
The patient had been well until 10 weeks before this presentation, when back pain developed between the shoulder blades. The pain resolved during the next 2 weeks, without an intervention. Six weeks before this presentation, numbness developed in a bandlike distribution around her trunk, with involvement of the area between the shoulder blades and the area under the breasts.
Five weeks before this presentation, the numbness extended to the upper abdomen. The patient was unable to sit up from the supine position without using her arms, and she had abdominal distention. Four weeks before this presentation, paresthesia developed in the third, fourth, and fifth fingers of the left hand and the fourth and fifth fingers of the right hand. The patient was seen at a clinic at another hospital, and magnetic resonance imaging (MRI) of the spine was scheduled. However, 2 weeks before this presentation, the numbness extended to the genital area and urinary incontinence developed, prompting the patient to present to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported no fevers, night sweats, change in weight, arm weakness, leg weakness, or change in gait. She had a history of hypertension, hypothyroidism, and symptomatic spinal stenosis, for which she had undergone L4-L5 decompression and bilateral medial facetectomy 6 years before this presentation. She had also undergone open reduction and internal fixation of left tibial and fibular fractures that had resulted from a fall, as well as excision of a foreign body that had punctured the right thenar.
Three months before this presentation, the patient had noted an area of nonpruritic, nonpainful erythema (measuring 8 cm in diameter) on the left gluteal fold, surrounding what she had thought to be an insect bite. Fever did not develop, and the erythema resolved during the subsequent 4 weeks. The patient's only medication was levothyroxine, and she was allergic to penicillin. She drank alcohol rarely, had smoked tobacco in the past, and did not use illicit drugs. She was married and lived with her husband in a wooded area in northeastern Connecticut. She worked in health care. There was no family history of neurologic disease.
On examination, the temperature was 36.6[degrees]C, the blood pressure 144/75 mm Hg, the heart rate 84 beats per minute, and the respiratory rate 18 breaths per minute. The weight was 74.8 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 25.8. There was decreased sensation on the posterior and anterior trunk and abdomen. The abdomen was distended. The remainder of the general medical examination was normal. The blood glucose level was 291 mg per deciliter (16.2 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). The blood electrolyte levels were normal, as were the results of tests of renal and liver function, the complete blood count, and the differential count. Imaging studies were obtained.
Dr. H. Benjamin Harvey: MRI of the cervical, thoracic, and lumbar spine, performed without the administration of contrast material, revealed no spinal cord compression, cord signal abnormality, or epidural collection. There were multilevel degenerative changes of the spine, as well as postsurgical changes related to remote L4-L5 decompression, without associated high-grade spinal-canal stenosis or nerve-root impingement. The nerve roots of the conus medullaris and cauda equina appeared to be normal, and there was no evidence of thickening or clumping of the nerve roots.
Dr. Misra: The patient chose to seek neurologic evaluation for her symptoms, and 2 weeks later, she was seen in the outpatient neurology clinic of this hospital. She reported stable paresthesia of the hands, ongoing numbness of the trunk and abdomen, new numbness of the upper anterior legs, and a 5-day history of difficulty lifting the front part of her left foot when she walked. She also reported difficulty taking a deep breath and coughing.
On examination, the temperature was 36.4[degrees]C, the blood pressure 106/67 mm Hg, the heart rate 77 beats per minute, and the respiratory rate 16 breaths per minute. The patient's mental status was normal, as were the results of testing of the 2nd through 12th cranial nerves. Strength was 4/5 during flexion of the left wrist, 5/5 while the patient was gripping the examiner's fingers, 4/5 during dorsiflexion of the left foot, and 4/5 during extension of the left toes; strength was otherwise 5/5. When the patient attempted to walk on her heels, she was unable to keep her left forefoot from touching the floor. Diaphragmatic excursion, as measured by percussion along the posterior chest at the end of inspiration and expiration, was symmetric. There was diminished tone in the bilateral rectus abdominis muscles, with associated abdominal distention. The patient was unable to rise from the supine position without assistance from the examiner. There was diminished sensation in response to light touch and pinprick in a bandlike distribution around the T6 dermatome spanning to the T12 dermatome. Deep-tendon reflexes were absent at the biceps on the left side and at the ankles bilaterally. The remainder of the neurologic and medical examination was normal.
Laboratory testing revealed a glycated hemoglobin level of 11.8% (reference range, <5.7), an erythrocyte sedimentation rate of 25 mm per hour (reference range, <30), and normal levels of thyrotropin, creatine kinase, vitamin D, vitamin B12, and folate.
Dr. Harvey: Chest radiographs obtained in the inspiratory and expiratory views showed no evidence of parenchymal opacity, pleural effusion, or lymphadenopathy. Hemidiaphragmatic movement between inspiration and expiration was present bilaterally. On MRI of the thoracic and lumbar spine without contrast enhancement, the findings were stable, as compared with the previous study. On MRI of the thoracic spine with contrast enhancement, there was no evidence of abnormal cord or meningeal enhancement (Figure 1).	
Figure 1 
Dr. Misra: A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 58-year-old woman was seen in the outpatient neurology clinic of this hospital in early autumn because of hypoesthesia, paresthesia, and weakness.
The patient had been well until 10 weeks before this presentation, when back pain developed between the shoulder blades. The pain resolved during the next 2 weeks, without an intervention. Six weeks before this presentation, numbness developed in a bandlike distribution around her trunk, with involvement of the area between the shoulder blades and the area under the breasts.
Five weeks before this presentation, the numbness extended to the upper abdomen. The patient was unable to sit up from the supine position without using her arms, and she had abdominal distention. Four weeks before this presentation, paresthesia developed in the third, fourth, and fifth fingers of the left hand and the fourth and fifth fingers of the right hand. The patient was seen at a clinic at another hospital, and magnetic resonance imaging (MRI) of the spine was scheduled. However, 2 weeks before this presentation, the numbness extended to the genital area and urinary incontinence developed, prompting the patient to present to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported no fevers, night sweats, change in weight, arm weakness, leg weakness, or change in gait. She had a history of hypertension, hypothyroidism, and symptomatic spinal stenosis, for which she had undergone L4-L5 decompression and bilateral medial facetectomy 6 years before this presentation. She had also undergone open reduction and internal fixation of left tibial and fibular fractures that had resulted from a fall, as well as excision of a foreign body that had punctured the right thenar.
Three months before this presentation, the patient had noted an area of nonpruritic, nonpainful erythema (measuring 8 cm in diameter) on the left gluteal fold, surrounding what she had thought to be an insect bite. Fever did not develop, and the erythema resolved during the subsequent 4 weeks. The patient's only medication was levothyroxine, and she was allergic to penicillin. She drank alcohol rarely, had smoked tobacco in the past, and did not use illicit drugs. She was married and lived with her husband in a wooded area in northeastern Connecticut. She worked in health care. There was no family history of neurologic disease.
On examination, the temperature was 36.6[degrees]C, the blood pressure 144/75 mm Hg, the heart rate 84 beats per minute, and the respiratory rate 18 breaths per minute. The weight was 74.8 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 25.8. There was decreased sensation on the posterior and anterior trunk and abdomen. The abdomen was distended. The remainder of the general medical examination was normal. The blood glucose level was 291 mg per deciliter (16.2 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). The blood electrolyte levels were normal, as were the results of tests of renal and liver function, the complete blood count, and the differential count. Imaging studies were obtained.
Dr. H. Benjamin Harvey: MRI of the cervical, thoracic, and lumbar spine, performed without the administration of contrast material, revealed no spinal cord compression, cord signal abnormality, or epidural collection. There were multilevel degenerative changes of the spine, as well as postsurgical changes related to remote L4-L5 decompression, without associated high-grade spinal-canal stenosis or nerve-root impingement. The nerve roots of the conus medullaris and cauda equina appeared to be normal, and there was no evidence of thickening or clumping of the nerve roots.
Dr. Misra: The patient chose to seek neurologic evaluation for her symptoms, and 2 weeks later, she was seen in the outpatient neurology clinic of this hospital. She reported stable paresthesia of the hands, ongoing numbness of the trunk and abdomen, new numbness of the upper anterior legs, and a 5-day history of difficulty lifting the front part of her left foot when she walked. She also reported difficulty taking a deep breath and coughing.
On examination, the temperature was 36.4[degrees]C, the blood pressure 106/67 mm Hg, the heart rate 77 beats per minute, and the respiratory rate 16 breaths per minute. The patient's mental status was normal, as were the results of testing of the 2nd through 12th cranial nerves. Strength was 4/5 during flexion of the left wrist, 5/5 while the patient was gripping the examiner's fingers, 4/5 during dorsiflexion of the left foot, and 4/5 during extension of the left toes; strength was otherwise 5/5. When the patient attempted to walk on her heels, she was unable to keep her left forefoot from touching the floor. Diaphragmatic excursion, as measured by percussion along the posterior chest at the end of inspiration and expiration, was symmetric. There was diminished tone in the bilateral rectus abdominis muscles, with associated abdominal distention. The patient was unable to rise from the supine position without assistance from the examiner. There was diminished sensation in response to light touch and pinprick in a bandlike distribution around the T6 dermatome spanning to the T12 dermatome. Deep-tendon reflexes were absent at the biceps on the left side and at the ankles bilaterally. The remainder of the neurologic and medical examination was normal.
Laboratory testing revealed a glycated hemoglobin level of 11.8% (reference range, <5.7), an erythrocyte sedimentation rate of 25 mm per hour (reference range, <30), and normal levels of thyrotropin, creatine kinase, vitamin D, vitamin B12, and folate.
Dr. Harvey: Chest radiographs obtained in the inspiratory and expiratory views showed no evidence of parenchymal opacity, pleural effusion, or lymphadenopathy. Hemidiaphragmatic movement between inspiration and expiration was present bilaterally. On MRI of the thoracic and lumbar spine without contrast enhancement, the findings were stable, as compared with the previous study. On MRI of the thoracic spine with contrast enhancement, there was no evidence of abnormal cord or meningeal enhancement (Figure 1).	
Figure 1 
Dr. Misra: A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Lyme disease is the most likely diagnosis. The patient lives in a wooded area in northeastern Connecticut, a region endemic for Lyme disease. She also reported a nonpruritic, nonpainful erythema on the left gluteal fold, which could be erythema migrans, a characteristic rash of Lyme disease. The patient's symptoms of hypoesthesia, paresthesia, and weakness could be due to Lyme neuroborreliosis, a neurological complication of Lyme disease. The absence of abnormalities on MRI and other tests also supports the diagnosis of Lyme disease, as the disease can often present without any significant findings on imaging or laboratory tests.""
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        ""content"": ""The patient's symptoms of hypoesthesia, paresthesia, and weakness, along with the band-like distribution of numbness around her trunk and extending to her upper abdomen, suggest a neurological issue. The fact that she lives in a wooded area in northeastern Connecticut and had a recent history of a nonpruritic, nonpainful erythema surrounding what she thought was an insect bite, suggests the possibility of Lyme disease, which is endemic in that region and often presents with a characteristic \""bull's eye\"" rash. The patient's urinary incontinence and difficulty lifting the front part of her left foot when she walks (foot drop) are also consistent with neurological involvement. The absence of abnormalities on MRI of the spine rules out spinal cord compression or other structural causes. The absence of abnormalities on chest radiographs rules out respiratory causes for her difficulty taking a deep breath and coughing. The normal levels of thyrotropin, creatine kinase, vitamin D, vitamin B12, and folate rule out thyroid disease, muscle disease, and vitamin deficiencies as causes for her symptoms. \n\nDiagnosis: Lyme disease.""
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        ""content"": ""The patient is a 58-year-old woman presenting with hypoesthesia, paresthesia, and weakness. She has a history of hypertension, hypothyroidism, and symptomatic spinal stenosis. Her symptoms began with back pain, followed by numbness in a bandlike distribution around her trunk, weakness in her arms, abdominal distention, and urinary incontinence. She also reported paresthesia in her fingers. Her symptoms have been progressing over the course of several weeks. She lives in a wooded area in northeastern Connecticut. She also reported a nonpruritic, nonpainful erythema on her left gluteal fold that she thought was an insect bite. The differential diagnosis for this patient includes multiple sclerosis, transverse myelitis, Lyme disease, and Guillain-Barre syndrome. Multiple sclerosis and transverse myelitis can present with similar symptoms, but the patient's history of an insect bite and living in a wooded area in northeastern Connecticut, a region endemic for Lyme disease, makes Lyme disease a strong possibility. Guillain-Barre syndrome is less likely given the chronicity of her symptoms. Lyme disease can cause neurologic symptoms, including numbness and weakness, and can also cause a characteristic erythema migrans rash, which the patient may have had. The patient's symptoms and history are most consistent with Lyme disease.\n\nDiagnosis: Lyme disease.""
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}",Lyme disease,Y
10.1056/NEJMcpc1802830,"Case 33-2018: A 57-Year-Old Man with Confusion, Fever, Malaise, and Weight Loss","Hemoglobin (g/dl)   11.7 11.7
Hematocrit (%)   34.6 35.3
Red-cell count (per mm3
)   3,670,000 3,650,000
White-cell count (per mm3)   18,720 23,820
Differential count (%)
Neutrophils   84.2
Lymphocytes   7.1
Monocytes   8.0
Eosinophils   0.0
Basophils   0.2
Platelet count (per mm3
)   147,000 96,000
Sodium (mmol/liter)   133 132
Potassium (mmol/liter)   3.8 4.3
Chloride (mmol/liter)   97 98
Carbon dioxide (mmol/liter)   21 20
Urea nitrogen (mg/dl)   11 18
Creatinine (mg/dl)   0.69 1.15
Glucose (mg/dl)   132 103
Calcium (mg/dl)   7.8 8.2
Magnesium (mg/dl)   1.8 2.8
Lactic acid (mmol/liter)   1.3 2.3
Total protein (g/dl) 6. .3 5.5 5.8
Albumin (g/dl)   2.7 2.7
Alanine aminotransferase (U/liter)   25 59
Aspartate aminotransferase (U/liter)   92 195
Prothrombin time (sec)   18.3 17.0
Prothrombin-time international normalized ratio   1.5 1.4
Troponin T (ng/ml) <0.03 1.39 2.55
N-terminal pro–B-type natriuretic peptide (pg/ml)   4107
Erythrocyte sedimentation rate (mm/hr)   8
C-reactive protein (mg/liter)  .0 197.9
Total cholesterol (mg/dl) <200 167
Low-density lipoprotein (mg/dl) 50–120 111
High-density lipoprotein (mg/dl)   22
Triglyceride (mg/dl)   169
Lactate dehydrogenase (U/liter) 11 10 1632
d-dimer (ng/ml)   >10,000
Fibrinogen (mg/dl) 15 0 215
Haptoglobin (mg/dl) 16–199 46
Venous blood gases
pH   7.34 7.29                                                                                                  Partial pressure of carbon dioxide (mm Hg)   44 51
Partial pressure of oxygen (mm Hg)   58 33
Urine
Bilirubin Negative Negative
Blood Negative Negative
Clarity Clear Slightly cloudy
Color Yellow Amber
Glucose Negative Negative
Ketones Negative 1+
Leukocyte esterase Negative Negative
Nitrites Negative Negative
pH   5.0
Protein Negative 2+
Erythrocytes (per high-power field)   3–5
Specific gravity   1.027
Urobilinogen Negative Negative
Leukocytes (per high-power field)   3–5","Pulmonary adenocarcinoma, complicated by a 
hypercoagulable state with nonbacterial thrombotic endocarditis.",Nonbacterial thrombotic endocarditis due to an underlying cancer.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 57-year-old man presented to this hospital with confusion, cough, fever, and unintentional weight loss.
The patient had been in his usual state of health until approximately 7 weeks before this presentation, when malaise and anorexia developed. Four weeks later, a nonproductive cough developed, along with fevers to a maximum temperature of 37.6[degrees]C, and the patient sought medical attention at another hospital. A chest radiograph showed an opacity in the left lower lobe (Figure 1A). In addition, computed tomography (CT) of the chest, performed without the intravenous administration of contrast material, revealed consolidation in the left lower lobe. The patient was admitted to the other hospital, and intravenous cefdinir and azithromycin were administered initially. The next day, treatment was switched to oral levofloxacin. After the patient had received levofloxacin for 6 days, he was discharged home.	
Figure 1 
One day after discharge, fever and cough persisted and the patient was readmitted to the other hospital. A sputum culture was obtained. Treatment with levofloxacin was stopped, and intravenous piperacillin-tazobactam and vancomycin were administered. After 2 days of parenteral therapy, the patient had some symptom relief; piperacillin-tazobactam and vancomycin were discontinued, and amoxicillin-clavulanic acid was administered. The patient was discharged home with a plan to complete a 10-day course of antibacterial therapy.
Fatigue, cough, and malaise continued. Night sweats and fevers to a maximum temperature of 37.8[degrees]C occurred daily, anorexia worsened, and weakness developed, such that the patient could not walk without assistance. Ten days after the second discharge (2 days before this presentation), the patient's wife noted that the patient was incoherent, disoriented, angry, and belligerent, and she found him urinating inappropriately around their home. On the evening of presentation, she found him showering while clothed. Emergency medical services were called, and the patient was taken to the other hospital.
On the patient's presentation to that hospital, the temperature was 38.3[degrees]C, the heart rate 111 beats per minute, the blood pressure 135/73 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 94% while he was breathing ambient air. He was confused and unable to answer questions appropriately. Laboratory test results were notable for a troponin I level of 13.4 ng per milliliter (reference range, <0.04), a lactate level of 2.4 mmol per liter (22 mg per deciliter [reference range, 0.4 to 2.0 mmol per liter; 6 to 18 mg per deciliter]), and a white-cell count of 21,800 per cubic millimeter (reference range, 4500 to 10,500). Blood cultures were obtained. Electrocardiography reportedly revealed sinus tachycardia, premature atrial beats, and submillimeter inferior ST-segment elevations. Because the patient had tachypnea and increased somnolence, the trachea was intubated and mechanical ventilation initiated. Intravenous vancomycin, piperacillin-tazobactam, ciprofloxacin, lorazepam, and propofol were administered, and the patient was transferred by helicopter to the emergency department of this hospital for consideration of coronary angiography.
On the patient's arrival at this hospital, a limited history was obtained from his wife. There was no report of chest pain, dyspnea, edema, or symptoms of arrhythmia. He had a history of eczema. He took no medications and had no known adverse reactions to medications, but he had a history of anaphylaxis to bee stings. The patient smoked cigarettes and had smoked 1 pack daily for the past 41 years; he also drank 8 to 10 beers per night, occasionally along with 2 to 3 glasses of wine, and smoked marijuana daily. He was a farmer, and he restored farmhouses and cleaned horse stables. He owned sheep and goats and had previously owned exotic birds. There was a family history of cancer; his sister had died of breast cancer at 42 years of age, and his father had died of an unknown cancer when he was in his 40s.
The temperature was 37.2[degrees]C, the heart rate 100 beats per minute, the blood pressure 120/82 mm Hg, and the oxygen saturation 100% while the patient was receiving mechanical ventilation at a rate of 18 breaths per minute, with a tidal volume of 500 ml, a positive end-expiratory pressure of 8 cm of water, and a fraction of inspired oxygen of 0.80. The pupils were 2 mm in diameter and sluggishly reactive. When the level of sedation was reduced, the patient opened his eyes and grimaced spontaneously but did not follow commands. He did not blink in response to threat or withdraw from noxious stimuli. The corneal reflexes were intact. The toes were downgoing bilaterally. There was no rash. The rest of the examination was normal.
Blood levels of phosphorus, bilirubin, alkaline phosphatase, globulin, lipase, glycated hemoglobin, and thyrotropin and the activated partial-thromboplastin time were normal; other laboratory test results are shown in Table 1. A serum test was negative for acetaminophen, ethanol, tricyclic antidepressants, and salicylates, but urine toxicology screening was positive for cannabinoids. Cultures of the blood, urine, and sputum were obtained. Nucleic-acid testing of a nasopharyngeal swab was negative for influenza virus types A and B and respiratory syncytial virus.	
Table 1 
An electrocardiogram showed sinus rhythm at 99 beats per minute, with 1-mm concave ST-segment elevations and PR-segment depressions in leads 2, 3, and aVF; a subtle PR-segment elevation in lead aVR; and submillimeter upsloping ST-segment depressions in lateral and anterior leads (Figure 1B). Imaging studies were obtained.
Dr. Melissa C. Price: A chest radiograph showed a persistent patchy opacity in the left lower lobe (Figure 2A), without evidence of pulmonary edema or pleural effusions. CT of the head, performed without the intravenous administration of contrast material, revealed subtle hypoattenuation and loss of differentiation between gray and white matter in the territory of the left middle cerebral artery, findings that raised concerns about an acute-to-subacute infarct; there was no evidence of intracranial hemorrhage. CT of the chest, abdomen, and pelvis, performed after the intravenous and oral administration of contrast material, revealed consolidation in the left lower lobe (Figure 2B), which had progressed since CT was last performed, 4 weeks earlier at the other hospital. Changes consistent with segmental and subsegmental pulmonary emboli were present in the right lower lobe, without evidence of strain on the right side of the heart. A wedge-shaped subpleural consolidation in the right lower lobe (Figure 2C) was consistent with a pulmonary infarct. There were new bilateral small pleural effusions. Multiple splenic and renal wedge-shaped hypoattenuating lesions were consistent with infarcts (Figure 2D).	
Figure 2 
Dr. Cohen: While the patient was in the emergency department, a 23-second episode of ventricular tachycardia occurred. Aspirin was administered rectally and magnesium and cefepime intravenously; infusions of propofol, normal saline, and amiodarone were also administered. Cardiac catheterization was considered but deferred. The patient was admitted to the intensive care unit. Additional imaging studies were obtained.
Dr. Price: Magnetic resonance imaging (MRI) and magnetic resonance angiography of the head and neck revealed numerous bilateral acute-to-subacute cerebral infarcts (Figure 2E) and punctate infarcts scattered throughout the cerebellar hemispheres. A few scattered punctate foci of susceptibility artifact raised concerns about microhemorrhages. Time-of-flight imaging revealed a linear susceptibility signal in the distal branches of the superior division of the left middle cerebral artery and loss of flow-related enhancement in the left superior middle cerebral artery, findings suggestive of thrombosis. Transthoracic echocardiography (TTE) was performed.
Dr. Danita Y. Sanborn: TTE revealed a left ventricular ejection fraction of 35%, with diffuse hypokinesis that was most prominent in the inferior territory. On studies obtained after the administration of agitated saline, there was no evidence of a patent foramen ovale. The mitral-valve leaflets were focally thickened, with mild-to-moderate mitral regurgitation. A small circumferential pericardial effusion was present (Figure 3A).	
Figure 3 
Dr. Cohen: Tests were negative for lupus anticoagulant, anticardiolipin IgM and IgG antibodies, [beta]2-glycoprotein IgM and IgG antibodies, anti-cyclic citrullinated peptide antibody, and anti-rheumatoid factor antibody; a test for antineutrophil antibody was positive at titers of 1:40 and 1:160, with a homogeneous pattern. Intravenous vancomycin and thiamine and enteral doxycycline, atorvastatin, omeprazole, and metoprolol were administered.
On the second day, the temperature was 38.4[degrees]C and repeat cultures of the blood, urine, and sputum were obtained. Tests were negative for anti-Ro (SSA), anti-La (SSB), and anti-Jo-1 antibodies, as well as IgM and IgG antibodies to brucella and coxiella (the agent causing Q fever) and antineutrophil cytoplasmic antibody. Ultrasonography of the arms and legs was negative for a thrombus. Bronchoscopy with bronchoalveolar lavage (BAL) revealed blood-tinged secretions in multiple airway segments. Gram staining of the BAL fluid revealed no leukocytes or organisms. Fungal wet preparation and acid-fast stains of the BAL fluid were negative, as was staining for Pneumocystis jiroveci and nucleic-acid testing for influenza virus types A and B and respiratory syncytial virus. In addition, direct fluorescence antibody testing of the BAL fluid was negative for adenovirus, human metapneumovirus, and parainfluenza virus types 1, 2, and 3.
A diagnostic test was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 57-year-old man presented to this hospital with confusion, cough, fever, and unintentional weight loss.
The patient had been in his usual state of health until approximately 7 weeks before this presentation, when malaise and anorexia developed. Four weeks later, a nonproductive cough developed, along with fevers to a maximum temperature of 37.6[degrees]C, and the patient sought medical attention at another hospital. A chest radiograph showed an opacity in the left lower lobe (Figure 1A). In addition, computed tomography (CT) of the chest, performed without the intravenous administration of contrast material, revealed consolidation in the left lower lobe. The patient was admitted to the other hospital, and intravenous cefdinir and azithromycin were administered initially. The next day, treatment was switched to oral levofloxacin. After the patient had received levofloxacin for 6 days, he was discharged home.	
Figure 1 
One day after discharge, fever and cough persisted and the patient was readmitted to the other hospital. A sputum culture was obtained. Treatment with levofloxacin was stopped, and intravenous piperacillin-tazobactam and vancomycin were administered. After 2 days of parenteral therapy, the patient had some symptom relief; piperacillin-tazobactam and vancomycin were discontinued, and amoxicillin-clavulanic acid was administered. The patient was discharged home with a plan to complete a 10-day course of antibacterial therapy.
Fatigue, cough, and malaise continued. Night sweats and fevers to a maximum temperature of 37.8[degrees]C occurred daily, anorexia worsened, and weakness developed, such that the patient could not walk without assistance. Ten days after the second discharge (2 days before this presentation), the patient's wife noted that the patient was incoherent, disoriented, angry, and belligerent, and she found him urinating inappropriately around their home. On the evening of presentation, she found him showering while clothed. Emergency medical services were called, and the patient was taken to the other hospital.
On the patient's presentation to that hospital, the temperature was 38.3[degrees]C, the heart rate 111 beats per minute, the blood pressure 135/73 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 94% while he was breathing ambient air. He was confused and unable to answer questions appropriately. Laboratory test results were notable for a troponin I level of 13.4 ng per milliliter (reference range, <0.04), a lactate level of 2.4 mmol per liter (22 mg per deciliter [reference range, 0.4 to 2.0 mmol per liter; 6 to 18 mg per deciliter]), and a white-cell count of 21,800 per cubic millimeter (reference range, 4500 to 10,500). Blood cultures were obtained. Electrocardiography reportedly revealed sinus tachycardia, premature atrial beats, and submillimeter inferior ST-segment elevations. Because the patient had tachypnea and increased somnolence, the trachea was intubated and mechanical ventilation initiated. Intravenous vancomycin, piperacillin-tazobactam, ciprofloxacin, lorazepam, and propofol were administered, and the patient was transferred by helicopter to the emergency department of this hospital for consideration of coronary angiography.
On the patient's arrival at this hospital, a limited history was obtained from his wife. There was no report of chest pain, dyspnea, edema, or symptoms of arrhythmia. He had a history of eczema. He took no medications and had no known adverse reactions to medications, but he had a history of anaphylaxis to bee stings. The patient smoked cigarettes and had smoked 1 pack daily for the past 41 years; he also drank 8 to 10 beers per night, occasionally along with 2 to 3 glasses of wine, and smoked marijuana daily. He was a farmer, and he restored farmhouses and cleaned horse stables. He owned sheep and goats and had previously owned exotic birds. There was a family history of cancer; his sister had died of breast cancer at 42 years of age, and his father had died of an unknown cancer when he was in his 40s.
The temperature was 37.2[degrees]C, the heart rate 100 beats per minute, the blood pressure 120/82 mm Hg, and the oxygen saturation 100% while the patient was receiving mechanical ventilation at a rate of 18 breaths per minute, with a tidal volume of 500 ml, a positive end-expiratory pressure of 8 cm of water, and a fraction of inspired oxygen of 0.80. The pupils were 2 mm in diameter and sluggishly reactive. When the level of sedation was reduced, the patient opened his eyes and grimaced spontaneously but did not follow commands. He did not blink in response to threat or withdraw from noxious stimuli. The corneal reflexes were intact. The toes were downgoing bilaterally. There was no rash. The rest of the examination was normal.
Blood levels of phosphorus, bilirubin, alkaline phosphatase, globulin, lipase, glycated hemoglobin, and thyrotropin and the activated partial-thromboplastin time were normal; other laboratory test results are shown in Table 1. A serum test was negative for acetaminophen, ethanol, tricyclic antidepressants, and salicylates, but urine toxicology screening was positive for cannabinoids. Cultures of the blood, urine, and sputum were obtained. Nucleic-acid testing of a nasopharyngeal swab was negative for influenza virus types A and B and respiratory syncytial virus.	
Table 1 
An electrocardiogram showed sinus rhythm at 99 beats per minute, with 1-mm concave ST-segment elevations and PR-segment depressions in leads 2, 3, and aVF; a subtle PR-segment elevation in lead aVR; and submillimeter upsloping ST-segment depressions in lateral and anterior leads (Figure 1B). Imaging studies were obtained.
Dr. Melissa C. Price: A chest radiograph showed a persistent patchy opacity in the left lower lobe (Figure 2A), without evidence of pulmonary edema or pleural effusions. CT of the head, performed without the intravenous administration of contrast material, revealed subtle hypoattenuation and loss of differentiation between gray and white matter in the territory of the left middle cerebral artery, findings that raised concerns about an acute-to-subacute infarct; there was no evidence of intracranial hemorrhage. CT of the chest, abdomen, and pelvis, performed after the intravenous and oral administration of contrast material, revealed consolidation in the left lower lobe (Figure 2B), which had progressed since CT was last performed, 4 weeks earlier at the other hospital. Changes consistent with segmental and subsegmental pulmonary emboli were present in the right lower lobe, without evidence of strain on the right side of the heart. A wedge-shaped subpleural consolidation in the right lower lobe (Figure 2C) was consistent with a pulmonary infarct. There were new bilateral small pleural effusions. Multiple splenic and renal wedge-shaped hypoattenuating lesions were consistent with infarcts (Figure 2D).	
Figure 2 
Dr. Cohen: While the patient was in the emergency department, a 23-second episode of ventricular tachycardia occurred. Aspirin was administered rectally and magnesium and cefepime intravenously; infusions of propofol, normal saline, and amiodarone were also administered. Cardiac catheterization was considered but deferred. The patient was admitted to the intensive care unit. Additional imaging studies were obtained.
Dr. Price: Magnetic resonance imaging (MRI) and magnetic resonance angiography of the head and neck revealed numerous bilateral acute-to-subacute cerebral infarcts (Figure 2E) and punctate infarcts scattered throughout the cerebellar hemispheres. A few scattered punctate foci of susceptibility artifact raised concerns about microhemorrhages. Time-of-flight imaging revealed a linear susceptibility signal in the distal branches of the superior division of the left middle cerebral artery and loss of flow-related enhancement in the left superior middle cerebral artery, findings suggestive of thrombosis. Transthoracic echocardiography (TTE) was performed.
Dr. Danita Y. Sanborn: TTE revealed a left ventricular ejection fraction of 35%, with diffuse hypokinesis that was most prominent in the inferior territory. On studies obtained after the administration of agitated saline, there was no evidence of a patent foramen ovale. The mitral-valve leaflets were focally thickened, with mild-to-moderate mitral regurgitation. A small circumferential pericardial effusion was present (Figure 3A).	
Figure 3 
Dr. Cohen: Tests were negative for lupus anticoagulant, anticardiolipin IgM and IgG antibodies, [beta]2-glycoprotein IgM and IgG antibodies, anti-cyclic citrullinated peptide antibody, and anti-rheumatoid factor antibody; a test for antineutrophil antibody was positive at titers of 1:40 and 1:160, with a homogeneous pattern. Intravenous vancomycin and thiamine and enteral doxycycline, atorvastatin, omeprazole, and metoprolol were administered.
On the second day, the temperature was 38.4[degrees]C and repeat cultures of the blood, urine, and sputum were obtained. Tests were negative for anti-Ro (SSA), anti-La (SSB), and anti-Jo-1 antibodies, as well as IgM and IgG antibodies to brucella and coxiella (the agent causing Q fever) and antineutrophil cytoplasmic antibody. Ultrasonography of the arms and legs was negative for a thrombus. Bronchoscopy with bronchoalveolar lavage (BAL) revealed blood-tinged secretions in multiple airway segments. Gram staining of the BAL fluid revealed no leukocytes or organisms. Fungal wet preparation and acid-fast stains of the BAL fluid were negative, as was staining for Pneumocystis jiroveci and nucleic-acid testing for influenza virus types A and B and respiratory syncytial virus. In addition, direct fluorescence antibody testing of the BAL fluid was negative for adenovirus, human metapneumovirus, and parainfluenza virus types 1, 2, and 3.
A diagnostic test was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of confusion, cough, fever, and unintentional weight loss, along with the history of daily alcohol and marijuana use, suggest a systemic infection. The patient's occupation as a farmer and his contact with animals suggest a zoonotic infection. The patient's symptoms did not improve with multiple courses of antibiotics, suggesting that the infection may be resistant to these drugs or caused by a non-bacterial pathogen. The presence of multiple infarcts in the brain, spleen, and kidneys suggests a condition causing widespread blood clots. The patient's positive urine test for cannabinoids is consistent with his reported daily marijuana use, but is not likely to be the cause of his symptoms. The patient's positive test for antineutrophil antibodies suggests an autoimmune condition, but this alone is not enough to explain all of his symptoms. The presence of multiple infarcts in the absence of a clear source of emboli suggests a hypercoagulable state. Taken together, these findings suggest a diagnosis of disseminated intravascular coagulation (DIC), likely secondary to a severe systemic infection.\n\nDiagnosis: Disseminated intravascular coagulation secondary to severe systemic infection.""
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        ""content"": ""This is a 57-year-old man who presents with confusion, cough, fever, and unintentional weight loss. He has a history of smoking and heavy alcohol use. He also has a history of exposure to farm animals and birds. His symptoms started with malaise and anorexia, followed by a nonproductive cough and fevers. Despite multiple courses of antibiotics, his symptoms persisted and he developed neurological symptoms. His lab results showed an elevated white blood cell count and troponin level. Imaging showed multiple infarcts in the brain, lungs, spleen, and kidneys. His symptoms and imaging findings suggest a systemic disease causing multiple infarcts. The differential diagnosis includes infective endocarditis, vasculitis, and disseminated intravascular coagulation (DIC). Given his history of exposure to farm animals and birds, zoonotic infections such as Q fever or psittacosis could also be considered. However, his lab results were negative for these infections. His positive antineutrophil antibody test suggests an autoimmune process, but his negative antineutrophil cytoplasmic antibody test makes vasculitis less likely. His history of heavy alcohol use could contribute to DIC, but his normal activated partial-thromboplastin time makes this less likely. His history of smoking and heavy alcohol use, along with his elevated troponin level, suggest possible cardiovascular disease, which could cause emboli leading to multiple infarcts. However, his echocardiogram did not show any evidence of a patent foramen ovale or vegetations on the heart valves, making this less likely. Given his history of exposure to farm animals and birds, his persistent fevers despite antibiotics, and his multiple infarcts, the most likely diagnosis is infective endocarditis. His negative blood cultures could be due to prior antibiotic use. \n\nDiagnosis: Infective endocarditis.""
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10.1056/NEJMcpc1712230,Case 32-2018: A 36-Year-Old Pregnant Woman with Newly Diagnosed Adenocarcinoma,"Hemoglobin (g/dl)  13.1 11.2   10.2
Hematocrit (%)  37.6 36.0–48.0 32.1   30.5
White-cell count (per mm3) 400 ,000 10,150   9950   14,310
Platelet count (per mm3) 135,00 0,000 292,000   231,000   264,000
Sodium (mmol/liter)   130   131   131
Potassium (mmol/liter)  4.6   3.5   3.9
Chloride (mmol/liter)   95 98–107 95   97
Carbon dioxide (mmol/liter) 2 1 10 22–31 22   20
Urea nitrogen (mg/dl)  6  <3   4
Creatinine (mg/dl)  0.57   0.44   0.37
Glucose (mg/dl) 74–106 99 70–100 130   121
Calcium (mg/dl) 8.7–10.4 9.0 8.8–10.7 7.8   8.4
Uric acid (mg/dl) 2.6–6.0 11.9 2.4–5.7 5.0 2.3–6.6
Albumin (g/dl)  3.1   2.7
Aspartate aminotransferase (U/liter)  47 10–50 74   103
Alanine aminotransferase (U/liter)  36 10–50 38   66
Bilirubin (mg/dl)  1.2 0.9 
Alkaline phosphatase (U/liter) 3 0 178   229
Lactate dehydrogenase (U/liter) 12 46 777 135–225 943
Hepatitis A virus total antibody Negative Negative
Hepatitis A virus IgG antibody Nonreactive Nonreactive
Hepatitis B virus surface antibody Nonreactive Nonreactive
Hepatitis B virus surface antigen Nonreactive Nonreactive
Hepatitis B virus core antibody Nonreactive Nonreactive
Hepatitis C virus total antibody Nonreactive Nonreactive
Carcinoembryonic antigen (ng/ml) 0–5.3 60.2  .5 35.5 <3.4
CA 19–9 (U/ml) 0–55 68 <35
Alpha-fetoprotein (ng/ml)  .3 560.4  .3 529.0
CA-125 (U/ml)  4 361  5","Poorly differentiated primary adenocarcinoma of the colon, with moderately differentiated metastatic adenocarcinoma in the liver and poorly differentiated metastatic carcinoma in the placenta.",Pregnancy at 33 weeks 4 days of gestation and metastatic colon cancer.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 36-year-old pregnant woman was evaluated at this hospital at 33 weeks of gestation because of newly diagnosed adenocarcinoma.
Seven months before this admission, when the patient was at her initial routine prenatal visit, transvaginal ultrasonography revealed a normal gestational sac and embryo. Thereafter, prenatal follow-up was uneventful, although she had abnormal results on a 1-hour glucose tolerance test at 27 weeks of gestation.
One week before the current evaluation, at 32 weeks of gestation, the patient had 3 days of nonradiating, severe pain in the lower back that she rated at 10 on a scale of 0 to 10, with 10 indicating the most severe pain. The pain started in the epigastric region and then migrated to the right upper quadrant and lower back. It was accompanied by severe nausea and an inability to eat any food or drink liquid without vomiting. She had night sweats and difficulty sleeping because of back pain. Four days after the pain began, the patient was admitted to the obstetrics service of another hospital.
On examination, the temperature was 36.6[degrees]C, the heart rate 96 beats per minute, the blood pressure 105/68 mm Hg, and the oxygen saturation 97% while the patient was breathing ambient air. She appeared to be uncomfortable. There was tenderness in the right upper quadrant, and the gravid uterus was soft. There was no costovertebral tenderness. The remainder of the examination was normal. The amylase and lipase levels and the white-cell differential count were normal; additional laboratory test results are shown in Table 1.	
Table 1
Fetal heart tones were noted on Doppler ultrasonography, and the measurements of the fetus on ultrasonography were appropriate for gestational age. The fetal biophysical profile (breathing motion, movement, tone, and amniotic-fluid volume) was reportedly normal.
Dr. Kimberly Shampain: On renal ultrasonography, the kidneys and bladder appeared normal but the liver was incidentally noted to be diffusely heterogeneous and nodular and to contain numerous masses. Abdominal magnetic resonance imaging (MRI), performed without the intravenous administration of contrast material, revealed multiple lesions in the liver that were mildly hyperintense on T2-weighted images and hypointense on T1-weighted images; the largest lesion measured 7.4 cm by 3.9 cm, and some lesions had central necrosis (Fig. 1A).	
Figure 1 
Dr. Prabhu: Allopurinol, an injection of betamethasone acetate-betamethasone sodium phosphate, and intravenous fluids were administered. One day after admission to the first hospital, the patient was transferred to the obstetrics service of a second hospital for further evaluation. Additional imaging studies were obtained.
Dr. Shampain: Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the intravenous administration of contrast material, revealed numerous hypoattenuating hepatic lesions, some with well-defined borders and others with ill-defined, irregular borders; the largest measured 8.2 cm in diameter. Multiple enlarged periaortic and portocaval lymph nodes were present (Fig. 1B).
Dr. Prabhu: Additional laboratory test results are shown in Table 1. A percutaneous liver biopsy was performed, and examination of the biopsy specimen revealed evidence suggestive of metastatic adenocarcinoma. Plans for chemotherapy were discussed, as was early fetal delivery. One week after admission to the second hospital, the patient left against medical advice. She presented to her obstetrician's office the next day, at 33 weeks of gestation, and then she was transferred to the obstetrics service of this hospital.
On evaluation at this hospital, the patient reported ongoing severe back pain. She had no vaginal bleeding or contractions. The temperature was 36.2[degrees]C, the blood pressure 114/74 mm Hg, and the oxygen saturation 97% while she was breathing ambient air. There was no abdominal tenderness, and fetal movement was detectable in the gravid uterus. The fetal heart rate was 125 beats per minute, with moderate variability and accelerations and without decelerations.
Additional history was obtained. Four years earlier, the patient had had a spontaneous abortion at 10 weeks of gestation. Medications included a prenatal vitamin with ferrous sulfate and folate. The patient had no known allergies. She was originally from Asia and lived in a suburb of Boston. She was married and was a college professor. She did not smoke tobacco, drink alcohol, or use any illicit substances. Her father had diabetes mellitus and hypertension, and her maternal grandfather had cancer, the details of which were unknown to the patient.
Management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 36-year-old pregnant woman was evaluated at this hospital at 33 weeks of gestation because of newly diagnosed adenocarcinoma.
Seven months before this admission, when the patient was at her initial routine prenatal visit, transvaginal ultrasonography revealed a normal gestational sac and embryo. Thereafter, prenatal follow-up was uneventful, although she had abnormal results on a 1-hour glucose tolerance test at 27 weeks of gestation.
One week before the current evaluation, at 32 weeks of gestation, the patient had 3 days of nonradiating, severe pain in the lower back that she rated at 10 on a scale of 0 to 10, with 10 indicating the most severe pain. The pain started in the epigastric region and then migrated to the right upper quadrant and lower back. It was accompanied by severe nausea and an inability to eat any food or drink liquid without vomiting. She had night sweats and difficulty sleeping because of back pain. Four days after the pain began, the patient was admitted to the obstetrics service of another hospital.
On examination, the temperature was 36.6[degrees]C, the heart rate 96 beats per minute, the blood pressure 105/68 mm Hg, and the oxygen saturation 97% while the patient was breathing ambient air. She appeared to be uncomfortable. There was tenderness in the right upper quadrant, and the gravid uterus was soft. There was no costovertebral tenderness. The remainder of the examination was normal. The amylase and lipase levels and the white-cell differential count were normal; additional laboratory test results are shown in Table 1.	
Table 1
Fetal heart tones were noted on Doppler ultrasonography, and the measurements of the fetus on ultrasonography were appropriate for gestational age. The fetal biophysical profile (breathing motion, movement, tone, and amniotic-fluid volume) was reportedly normal.
Dr. Kimberly Shampain: On renal ultrasonography, the kidneys and bladder appeared normal but the liver was incidentally noted to be diffusely heterogeneous and nodular and to contain numerous masses. Abdominal magnetic resonance imaging (MRI), performed without the intravenous administration of contrast material, revealed multiple lesions in the liver that were mildly hyperintense on T2-weighted images and hypointense on T1-weighted images; the largest lesion measured 7.4 cm by 3.9 cm, and some lesions had central necrosis (Fig. 1A).	
Figure 1 
Dr. Prabhu: Allopurinol, an injection of betamethasone acetate-betamethasone sodium phosphate, and intravenous fluids were administered. One day after admission to the first hospital, the patient was transferred to the obstetrics service of a second hospital for further evaluation. Additional imaging studies were obtained.
Dr. Shampain: Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the intravenous administration of contrast material, revealed numerous hypoattenuating hepatic lesions, some with well-defined borders and others with ill-defined, irregular borders; the largest measured 8.2 cm in diameter. Multiple enlarged periaortic and portocaval lymph nodes were present (Fig. 1B).
Dr. Prabhu: Additional laboratory test results are shown in Table 1. A percutaneous liver biopsy was performed, and examination of the biopsy specimen revealed evidence suggestive of metastatic adenocarcinoma. Plans for chemotherapy were discussed, as was early fetal delivery. One week after admission to the second hospital, the patient left against medical advice. She presented to her obstetrician's office the next day, at 33 weeks of gestation, and then she was transferred to the obstetrics service of this hospital.
On evaluation at this hospital, the patient reported ongoing severe back pain. She had no vaginal bleeding or contractions. The temperature was 36.2[degrees]C, the blood pressure 114/74 mm Hg, and the oxygen saturation 97% while she was breathing ambient air. There was no abdominal tenderness, and fetal movement was detectable in the gravid uterus. The fetal heart rate was 125 beats per minute, with moderate variability and accelerations and without decelerations.
Additional history was obtained. Four years earlier, the patient had had a spontaneous abortion at 10 weeks of gestation. Medications included a prenatal vitamin with ferrous sulfate and folate. The patient had no known allergies. She was originally from Asia and lived in a suburb of Boston. She was married and was a college professor. She did not smoke tobacco, drink alcohol, or use any illicit substances. Her father had diabetes mellitus and hypertension, and her maternal grandfather had cancer, the details of which were unknown to the patient.
Management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with severe pain in the lower back and right upper quadrant, severe nausea, and vomiting. She also has night sweats and difficulty sleeping due to back pain. Imaging reveals multiple lesions in the liver and enlarged periaortic and portocaval lymph nodes. A liver biopsy reveals metastatic adenocarcinoma. Given these findings, the patient's diagnosis is metastatic adenocarcinoma of unknown primary origin.""
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        ""content"": ""The patient is a 36-year-old pregnant woman who presents with severe back pain, nausea, vomiting, and night sweats. She has been found to have multiple lesions in the liver and enlarged periaortic and portocaval lymph nodes. A liver biopsy has revealed metastatic adenocarcinoma. The primary site of the adenocarcinoma is not clear from the information given. However, given the patient's gender and the fact that she is pregnant, the differential diagnosis for the primary site of the adenocarcinoma should include breast, lung, gastrointestinal tract, pancreas, and gynecological organs such as the ovary, endometrium, and cervix. The patient does not have any respiratory symptoms, making lung cancer less likely. She also does not have any gastrointestinal symptoms such as changes in bowel habits, blood in stool, or abdominal pain, making gastrointestinal cancer less likely. She does not have any symptoms of pancreatic cancer such as jaundice, light-colored stools, or dark urine. She does not have any symptoms of gynecological cancer such as abnormal vaginal bleeding or discharge. However, she does have severe back pain, which could be a symptom of metastatic breast cancer. Therefore, the most likely diagnosis is metastatic adenocarcinoma of the breast. \n\nDiagnosis: Metastatic adenocarcinoma of the breast.""
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10.1056/NEJMcpc1802831,Case 30-2018: A 66-Year-Old Woman with Chronic Abdominal Pain,"Hematocrit (%)   42.1 39.5
Hemoglobin (g/dl)   14.1 13.1
White-cell count (per mm3)   9430 13,500
Differential count (%)
Neutrophils   58.1 52.0
Lymphocytes   31.3 22.4
Monocytes   6.3 5.0
Eosinophils   3.8 19.5
Basophils   0.3 0.5
Platelet count (per mm3)   349,000 406,000
Red-cell count (per mm3) 4,000,000–5,200,000 4,870,000 4,440,000
Mean corpuscular volume (fl)   86.4 89.0
Red-cell distribution width (%)   13.2 12.5
Alkaline phosphatase (U/liter)   177 119
Bilirubin (mg/dl)†
Total 0–1.0 0.4 0.2
Direct   <0.2 <0.2
Alanine aminotransferase (U/liter)   62 17
Aspartate aminotransferase (U/liter)   40 19
Albumin (g/dl)   4.4 4.3
Lipase (U/liter) 13–60 30","Colonic mass due to infection with an intravascular nematode, most likely Angiostrongylus costaricensis","Intestinal helminthiasis, but colon cancer cannot be ruled out.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 66-year-old woman presented to a community health center affiliated with this hospital for an initial evaluation and to establish care with a primary care provider.
The patient had been in her usual state of health until 5 months before presentation, when fevers and throbbing pain in the left ear and on the left side of the face developed. The pain radiated to the jaw and was associated with neck stiffness and tinnitus. She was evaluated by a physician in Guatemala, where she was living when the symptoms began. Computed tomography (CT) of the head reportedly revealed findings consistent with sinusitis and otitis media of the left ear. The fevers and neck stiffness resolved without specific treatment, but the ear and facial pain persisted and did not diminish with the use of acetaminophen.
On presentation to the community health center, the patient reported an intentional weight loss of 7 kg during the 6 months before presentation, which she attributed to changes in her diet. She had no fever, night sweats, rash, chest pain, or shortness of breath. She had a history of hypertension and dyslipidemia. Dull, waxing and waning pain in the left side of the abdomen, which had begun after the birth of her youngest child, had not changed in location, quality, or intensity during the past 30 years.
Two years before presentation to the community health center, episodes of epigastric pain had developed. The pain was burning in quality, radiated toward the chest, occurred most frequently after meals, and was associated with diarrhea. At that time, the patient was evaluated by a physician in Guatemala, and testing reportedly revealed Helicobacter pylori infection. She was not treated with antibiotic agents, but the epigastric pain diminished with the administration of intermittent proton-pump inhibitor therapy.
Ten months before presentation to the community health center, the patient had been visiting New England and had presented to the emergency department of this hospital for evaluation of epigastric pain. The epigastric pain was similar to previous episodes but did not diminish after 3 days of proton-pump inhibitor therapy. She reported no dark stools, fevers, chills, or sick contacts. On examination, the temperature was 36.6[degrees]C, the blood pressure 134/74 mm Hg, the heart rate 72 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The weight was 71.7 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 32. The patient appeared to be well. The abdomen was tender on palpation of the epigastric area, without rebound or guarding. The bowel sounds were normal, and there was no palpable abdominal mass or hepatosplenomegaly. The remainder of the physical examination was normal. Urinalysis, results of kidney-function tests, and blood levels of glucose, electrolytes, and lipase were normal; other laboratory tests results are shown in Table 1. Stool culture revealed normal enteric flora. Examination of the stool for H. pylori antigen was negative. The patient was referred to a primary care clinic in New England for further evaluation, but the abdominal pain resolved and she returned to Guatemala.	
Table 1 
On evaluation at the community health center, medications included alprazolam, aspirin, amiloride-hydrochlorothiazide, bisoprolol, and ciprofibrate. The patient was not taking any other nonsteroidal antiinflammatory drugs (NSAIDs) or herbal supplements. She did not smoke tobacco, drink alcohol, or use illicit drugs. She lived in a small, rural town in Guatemala. She often ate boiled fish, shrimp, and crayfish from the freshwater rivers around her home. She worked as a midwife and made frequent trips to New England to visit family. There was no family history of cancer or heart disease; several family members had been exposed to tuberculosis.
On examination, the weight was 65.8 kg and the BMI 29. There was tenderness on palpation of the left temporomandibular joint, temporal region, and cheek. The left jaw clicked with opening. There was no cervical lymphadenopathy. There was a systolic crescendo-decrescendo murmur, grade 2/6, that was best heard at the right upper sternal border. The bowel sounds were normal, and the abdomen was soft, without distention, mass, tenderness, rebound, or guarding. The remainder of the examination was normal. The glycated hemoglobin level was 5.6% (reference range, 4.3 to 6.4), and a lipid panel was normal. Tests for hepatitis A virus IgM antibodies, hepatitis B virus surface antigen, hepatitis B virus surface antibodies, hepatitis B virus core antibodies, and hepatitis C virus antibodies were negative; other laboratory test results are shown in Table 1.
Acetaminophen and jaw exercises with massage were recommended for the facial pain. The patient was referred for mammography and colonoscopy for age-appropriate cancer screening. Two days later, an interferon-[gamma] release assay for Mycobacterium tuberculosis was positive, and a chest radiograph was obtained.
Dr. Kristine S. Burk: The chest radiograph showed normal mediastinal contours without evidence of lymphadenopathy or cardiomegaly, clear pleural spaces without evidence of an effusion, and clear lungs without evidence of opacities, apical scarring, or calcified granulomas.
Dr. Henderson-Frost: One month after the initial visit, the patient returned to the community health center to discuss treatment options for latent tuberculosis infection. At that time, she reported a 2-month history of intermittent pain in the right upper and lower quadrants that had not been discussed at the previous visit. The physical examination was unchanged. CT of the abdomen was performed.
Dr. Burk: CT of the abdomen and pelvis, performed after the intravenous and oral administration of contrast material (Figure 1), revealed an irregular, circumferential mass in the ascending colon that measured 4.5 cm in the craniocaudal dimension and had transmural extension. There was stranding in the adjacent pericolonic fat, and there were multiple adjacent enlarged mesenteric lymph nodes. The appendix had mild wall thickening but was not dilated, and it contained air and stool; these features were consistent with inflammation related to the adjacent process in the ascending colon.	
Figure 1 
Dr. Kyle Staller: The patient was referred for expedited colonoscopy. When the procedure was performed (Figure 2), sessile polyps, measuring 3 mm in diameter, were detected in the sigmoid colon and the descending colon. The polyps were removed by cold snare polypectomy. There was an infiltrative noncircumferential, nonobstructing mass in the ascending colon, along with scant bleeding. Biopsy specimens of the mass were obtained.	
Figure 2
Dr. Vikram Deshpande: Histologic evaluation of the resected polyps showed tubular adenomas. Histologic evaluation of the biopsy specimens of the mass showed ulcerated mucosa with extensive granulation tissue, with evidence of acute and chronic inflammation and reactive changes, including numerous plasma cells and histiocytes.
Dr. Henderson-Frost: On the basis of the colonoscopy results, a carcinoembryonic antigen level was obtained, and it was 2.2 ng per milliliter (reference range, <3.4). A diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 66-year-old woman presented to a community health center affiliated with this hospital for an initial evaluation and to establish care with a primary care provider.
The patient had been in her usual state of health until 5 months before presentation, when fevers and throbbing pain in the left ear and on the left side of the face developed. The pain radiated to the jaw and was associated with neck stiffness and tinnitus. She was evaluated by a physician in Guatemala, where she was living when the symptoms began. Computed tomography (CT) of the head reportedly revealed findings consistent with sinusitis and otitis media of the left ear. The fevers and neck stiffness resolved without specific treatment, but the ear and facial pain persisted and did not diminish with the use of acetaminophen.
On presentation to the community health center, the patient reported an intentional weight loss of 7 kg during the 6 months before presentation, which she attributed to changes in her diet. She had no fever, night sweats, rash, chest pain, or shortness of breath. She had a history of hypertension and dyslipidemia. Dull, waxing and waning pain in the left side of the abdomen, which had begun after the birth of her youngest child, had not changed in location, quality, or intensity during the past 30 years.
Two years before presentation to the community health center, episodes of epigastric pain had developed. The pain was burning in quality, radiated toward the chest, occurred most frequently after meals, and was associated with diarrhea. At that time, the patient was evaluated by a physician in Guatemala, and testing reportedly revealed Helicobacter pylori infection. She was not treated with antibiotic agents, but the epigastric pain diminished with the administration of intermittent proton-pump inhibitor therapy.
Ten months before presentation to the community health center, the patient had been visiting New England and had presented to the emergency department of this hospital for evaluation of epigastric pain. The epigastric pain was similar to previous episodes but did not diminish after 3 days of proton-pump inhibitor therapy. She reported no dark stools, fevers, chills, or sick contacts. On examination, the temperature was 36.6[degrees]C, the blood pressure 134/74 mm Hg, the heart rate 72 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The weight was 71.7 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 32. The patient appeared to be well. The abdomen was tender on palpation of the epigastric area, without rebound or guarding. The bowel sounds were normal, and there was no palpable abdominal mass or hepatosplenomegaly. The remainder of the physical examination was normal. Urinalysis, results of kidney-function tests, and blood levels of glucose, electrolytes, and lipase were normal; other laboratory tests results are shown in Table 1. Stool culture revealed normal enteric flora. Examination of the stool for H. pylori antigen was negative. The patient was referred to a primary care clinic in New England for further evaluation, but the abdominal pain resolved and she returned to Guatemala.	
Table 1 
On evaluation at the community health center, medications included alprazolam, aspirin, amiloride-hydrochlorothiazide, bisoprolol, and ciprofibrate. The patient was not taking any other nonsteroidal antiinflammatory drugs (NSAIDs) or herbal supplements. She did not smoke tobacco, drink alcohol, or use illicit drugs. She lived in a small, rural town in Guatemala. She often ate boiled fish, shrimp, and crayfish from the freshwater rivers around her home. She worked as a midwife and made frequent trips to New England to visit family. There was no family history of cancer or heart disease; several family members had been exposed to tuberculosis.
On examination, the weight was 65.8 kg and the BMI 29. There was tenderness on palpation of the left temporomandibular joint, temporal region, and cheek. The left jaw clicked with opening. There was no cervical lymphadenopathy. There was a systolic crescendo-decrescendo murmur, grade 2/6, that was best heard at the right upper sternal border. The bowel sounds were normal, and the abdomen was soft, without distention, mass, tenderness, rebound, or guarding. The remainder of the examination was normal. The glycated hemoglobin level was 5.6% (reference range, 4.3 to 6.4), and a lipid panel was normal. Tests for hepatitis A virus IgM antibodies, hepatitis B virus surface antigen, hepatitis B virus surface antibodies, hepatitis B virus core antibodies, and hepatitis C virus antibodies were negative; other laboratory test results are shown in Table 1.
Acetaminophen and jaw exercises with massage were recommended for the facial pain. The patient was referred for mammography and colonoscopy for age-appropriate cancer screening. Two days later, an interferon-[gamma] release assay for Mycobacterium tuberculosis was positive, and a chest radiograph was obtained.
Dr. Kristine S. Burk: The chest radiograph showed normal mediastinal contours without evidence of lymphadenopathy or cardiomegaly, clear pleural spaces without evidence of an effusion, and clear lungs without evidence of opacities, apical scarring, or calcified granulomas.
Dr. Henderson-Frost: One month after the initial visit, the patient returned to the community health center to discuss treatment options for latent tuberculosis infection. At that time, she reported a 2-month history of intermittent pain in the right upper and lower quadrants that had not been discussed at the previous visit. The physical examination was unchanged. CT of the abdomen was performed.
Dr. Burk: CT of the abdomen and pelvis, performed after the intravenous and oral administration of contrast material (Figure 1), revealed an irregular, circumferential mass in the ascending colon that measured 4.5 cm in the craniocaudal dimension and had transmural extension. There was stranding in the adjacent pericolonic fat, and there were multiple adjacent enlarged mesenteric lymph nodes. The appendix had mild wall thickening but was not dilated, and it contained air and stool; these features were consistent with inflammation related to the adjacent process in the ascending colon.	
Figure 1 
Dr. Kyle Staller: The patient was referred for expedited colonoscopy. When the procedure was performed (Figure 2), sessile polyps, measuring 3 mm in diameter, were detected in the sigmoid colon and the descending colon. The polyps were removed by cold snare polypectomy. There was an infiltrative noncircumferential, nonobstructing mass in the ascending colon, along with scant bleeding. Biopsy specimens of the mass were obtained.	
Figure 2
Dr. Vikram Deshpande: Histologic evaluation of the resected polyps showed tubular adenomas. Histologic evaluation of the biopsy specimens of the mass showed ulcerated mucosa with extensive granulation tissue, with evidence of acute and chronic inflammation and reactive changes, including numerous plasma cells and histiocytes.
Dr. Henderson-Frost: On the basis of the colonoscopy results, a carcinoembryonic antigen level was obtained, and it was 2.2 ng per milliliter (reference range, <3.4). A diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with a history of abdominal pain and a recent intentional weight loss. She had a history of H. pylori infection and epigastric pain. A CT scan revealed an irregular, circumferential mass in the ascending colon with transmural extension and multiple adjacent enlarged mesenteric lymph nodes. Colonoscopy confirmed the presence of the mass and biopsy showed ulcerated mucosa with extensive granulation tissue, acute and chronic inflammation, and reactive changes. These findings are consistent with a diagnosis of colon cancer. \n\nDiagnosis: Colon Cancer""
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        ""content"": ""The patient's symptoms include persistent ear and facial pain, weight loss, and abdominal pain. The CT scan revealed an irregular, circumferential mass in the ascending colon with transmural extension and multiple adjacent enlarged mesenteric lymph nodes. The colonoscopy confirmed the presence of an infiltrative noncircumferential, nonobstructing mass in the ascending colon. Histologic evaluation of the biopsy specimens of the mass showed ulcerated mucosa with extensive granulation tissue, with evidence of acute and chronic inflammation and reactive changes, including numerous plasma cells and histiocytes. These findings are consistent with a diagnosis of colon cancer. \n\nDiagnosis: Colon Cancer""
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        ""content"": ""The patient is a 66-year-old woman with a history of hypertension and dyslipidemia who presents with persistent left ear and facial pain, weight loss, and abdominal pain. She has a history of H. pylori infection and has been experiencing episodes of epigastric pain. The differential diagnosis for this patient includes otitis media, sinusitis, temporomandibular joint disorder, gastrointestinal disorders such as peptic ulcer disease or gastritis, and malignancies such as colon cancer. The patient's ear and facial pain could be due to otitis media or sinusitis, but these conditions would not explain her abdominal pain or weight loss. Temporomandibular joint disorder could explain the facial pain and clicking of the jaw, but again, would not account for the abdominal symptoms or weight loss. The patient's history of H. pylori infection and epigastric pain suggest a gastrointestinal disorder such as peptic ulcer disease or gastritis, but these conditions would not typically cause weight loss unless they were severe. The patient's weight loss, abdominal pain, and the findings of an irregular mass in the ascending colon on CT scan raise concern for a malignancy such as colon cancer. The biopsy of the mass showed ulcerated mucosa with extensive granulation tissue, acute and chronic inflammation, and reactive changes, which could be consistent with a malignancy or an inflammatory process. However, the carcinoembryonic antigen level was within normal limits, which makes colon cancer less likely. \n\nDiagnosis: Inflammatory bowel disease, possibly Crohn's disease.""
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10.1056/NEJMcpc1807497,Case 29-2018: A 31-Year-Old Woman with Infertility,"Human chorionic gonadotropin (IU/liter) <6 <6
Follicle-stimulating hormone (IU/liter) 18. 3.0 in postmenopause
3. 0.0 in premenopause during the follicular phase
9. 6.0 in premenopause during the ovulatory phase
1.0–12.0 in premenopause during the luteal phase
1.9 2.1
Luteinizing hormone (IU/liter) 16.0–64.0 in postmenopause
2. .0 in premenopause during the follicular phase
22.0–105.0 in premenopause during the ovulatory phase
0.6–19.0 in premenopause during the luteal phase
25.5
Estradiol (pg/ml) <50 in postmenopause
27–156 in premenopause during the follicular phase
48–314 in premenopause during the ovulatory phase
33–298 in premenopause during the luteal phase
49 43
Progesterone (ng/ml)2.15 1.98
Prolactin (ng/ml) 6.4
Thyrotropin (μIU/ml) 0.4 0 1.42
Free thyroxine (ng/dl)  1.3",Complete androgen insensitivity syndrome,"Complete androgen insensitivity syndrome, with Sertoli-cell adenoma or another tumor with hypersecretion of inhibin B.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 31-year-old woman with infertility was referred to the fertility center of this hospital by a surrogate parenting agency to discuss the possibility of family building with an oocyte donor and a gestational carrier.
The patient reported that, when she was 16 years of age, she had been evaluated for primary amenorrhea and had received a diagnosis of congenital absence of the uterus and ovaries. When she was approximately 12 years of age, adrenarche and thelarche had occurred in association with a linear growth spurt. The patient had never had menstrual molimina or any headaches, vision problems, galactorrhea, vasomotor symptoms, or reduction in exercise tolerance.
The patient also reported that, when she was 10 years of age, she had fractured her arm and had undergone tonsillectomy. She took no medications and had no known allergies. Four months before the current evaluation, she had moved to New England from northern Europe; she currently lived with her husband in a suburban area and worked in an office. She drank alcohol rarely, smoked 3 to 5 cigarettes a day, and did not use illicit drugs. Her mother had conceived her children easily and had undergone hysterectomy because of endometriosis when she was 46 years of age, and her maternal grandfather had died of a myocardial infarction when he was 70 years of age. The patient's father and two sisters were healthy; one sister was the patient's fraternal twin and had regular menses.
On examination, the blood pressure was 118/74 mm Hg, the weight 68.1 kg, the height 172.7 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 22.8. The patient had minimal body hair. A pelvic examination revealed normal female external genitalia and normal vaginal length and rugae; there was no abnormal vaginal discharge or evidence of pelvic-organ prolapse. The cervix and uterus were absent. There was mild fullness in the left adnexal region, without tenderness or a discrete mass. The remainder of the physical examination was normal.
Ultrasonography of the pelvis confirmed the absence of the uterus and cervix. The right ovary was not visualized; there were clusters of simple cysts in the adnexal region on the right side (one measuring 24 mm by 25 mm and another measuring 18 mm by 17 mm) and on the left side (one measuring 18 mm by 17 mm and another measuring 20 mm by 21 mm). Tests were positive for rubella virus IgG antibodies and varicella-zoster virus IgG antibodies, and screening tests were negative for hepatitis B virus surface antigen, human immunodeficiency virus types 1 and 2, hepatitis C virus, human T-lymphotropic virus types 1 and 2, syphilis, and cytomegalovirus. The complete blood count and white-cell differential count were normal; other laboratory test results are shown in Table 1. Blood specimens were collected for measurement of the antimullerian hormone level and for chromosome analysis.	
Table 1 
Five days later, additional diagnostic tests were performed; laboratory test results are shown in Table 1. Dual-energy x-ray absorptiometry was performed for the assessment of bone mineral density. There was borderline low bone mass in the spine on posterior-anterior examination (bone mineral density T score, -1.10), normal bone mass in the vertebral bodies on lateral examination (T score, -0.20), and normal bone mass in the femoral neck (T score, -0.90).
Four days later, a diagnostic test result was received, and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 31-year-old woman with infertility was referred to the fertility center of this hospital by a surrogate parenting agency to discuss the possibility of family building with an oocyte donor and a gestational carrier.
The patient reported that, when she was 16 years of age, she had been evaluated for primary amenorrhea and had received a diagnosis of congenital absence of the uterus and ovaries. When she was approximately 12 years of age, adrenarche and thelarche had occurred in association with a linear growth spurt. The patient had never had menstrual molimina or any headaches, vision problems, galactorrhea, vasomotor symptoms, or reduction in exercise tolerance.
The patient also reported that, when she was 10 years of age, she had fractured her arm and had undergone tonsillectomy. She took no medications and had no known allergies. Four months before the current evaluation, she had moved to New England from northern Europe; she currently lived with her husband in a suburban area and worked in an office. She drank alcohol rarely, smoked 3 to 5 cigarettes a day, and did not use illicit drugs. Her mother had conceived her children easily and had undergone hysterectomy because of endometriosis when she was 46 years of age, and her maternal grandfather had died of a myocardial infarction when he was 70 years of age. The patient's father and two sisters were healthy; one sister was the patient's fraternal twin and had regular menses.
On examination, the blood pressure was 118/74 mm Hg, the weight 68.1 kg, the height 172.7 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 22.8. The patient had minimal body hair. A pelvic examination revealed normal female external genitalia and normal vaginal length and rugae; there was no abnormal vaginal discharge or evidence of pelvic-organ prolapse. The cervix and uterus were absent. There was mild fullness in the left adnexal region, without tenderness or a discrete mass. The remainder of the physical examination was normal.
Ultrasonography of the pelvis confirmed the absence of the uterus and cervix. The right ovary was not visualized; there were clusters of simple cysts in the adnexal region on the right side (one measuring 24 mm by 25 mm and another measuring 18 mm by 17 mm) and on the left side (one measuring 18 mm by 17 mm and another measuring 20 mm by 21 mm). Tests were positive for rubella virus IgG antibodies and varicella-zoster virus IgG antibodies, and screening tests were negative for hepatitis B virus surface antigen, human immunodeficiency virus types 1 and 2, hepatitis C virus, human T-lymphotropic virus types 1 and 2, syphilis, and cytomegalovirus. The complete blood count and white-cell differential count were normal; other laboratory test results are shown in Table 1. Blood specimens were collected for measurement of the antimullerian hormone level and for chromosome analysis.	
Table 1 
Five days later, additional diagnostic tests were performed; laboratory test results are shown in Table 1. Dual-energy x-ray absorptiometry was performed for the assessment of bone mineral density. There was borderline low bone mass in the spine on posterior-anterior examination (bone mineral density T score, -1.10), normal bone mass in the vertebral bodies on lateral examination (T score, -0.20), and normal bone mass in the femoral neck (T score, -0.90).
Four days later, a diagnostic test result was received, and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""This patient has a history of primary amenorrhea and a diagnosis of congenital absence of the uterus and ovaries. However, the presence of clusters of simple cysts in the adnexal region on both sides suggests the presence of ovarian tissue. The patient also has normal female external genitalia and normal vaginal length and rugae, which would not be expected in a case of complete androgen insensitivity syndrome. The patient's history and physical examination findings are consistent with a diagnosis of Mayer-Rokitansky-K\u00fcster-Hauser (MRKH) syndrome, a disorder characterized by congenital aplasia of the uterus and the upper part of the vagina in women showing normal development of secondary sexual characteristics and a normal 46,XX karyotype. \n\nDiagnosis: Mayer-Rokitansky-K\u00fcster-Hauser (MRKH) syndrome.""
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}",Mayer-Rokitansky-K\u00fcster-Hauser (MRKH) syndrome,N,"{
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        ""content"": ""This is a 31-year-old woman with primary amenorrhea and a history of congenital absence of the uterus and ovaries. The differential diagnosis for primary amenorrhea includes Turner syndrome, androgen insensitivity syndrome, and Mullerian agenesis. Turner syndrome is less likely because the patient had a normal growth spurt and does not have any of the characteristic physical features such as a webbed neck or low-set ears. Androgen insensitivity syndrome is also less likely because the patient has normal female external genitalia and no evidence of testes in the inguinal region. Mullerian agenesis, also known as Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, is a condition characterized by congenital absence of the uterus and upper two-thirds of the vagina in women with normal development of secondary sexual characteristics and a normal 46,XX karyotype. This patient's history and physical examination findings are consistent with MRKH syndrome. \n\nDiagnosis: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome.""
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}",Mayer-Rokitansky-K\u00fcster-Hauser (MRKH) syndrome,N
10.1056/NEJMcpc1807498,"Case 28-2018: A 39-Year-Old Man with Epistaxis, Pain and Erythema of the Forearm, and Pancytopenia","Hematocrit (%)   33.0
Hemoglobin (g/dl)   11.2
White-cell count (per mm3
) 400 ,000 1150
Differential count (%)
Neutrophils  31.2
Lymphocytes 25–33 60.9

Eosinophils   0.0
Band forms 0.3
Basophils   0.9
Platelet count (per mm3
)   37,000
Red-cell count (per mm3
) 4,000,000–5,900,000 3,620,000
Mean corpuscular volume (fl)   91.2
Red-cell distribution width (%)   15.9
Alkaline phosphatase (U/liter) 32–100 77
Bilirubin (mg/dl)
Total 0–1.2 0.7
Direct 0–0.2 0.2
Alanine aminotransferase (U/liter) 10–50 25
Aspartate aminotransferase (U/liter) 15–41 33
Albumin (g/dl) 3.5–5.2 4.2
Prothrombin time (sec) 12.1–14.7 15.3
International normalized ratio   1.2
Partial-thromboplastin time (sec) 22. 5.0 31.8
Lactate dehydrogenase (U/liter) 11 10 269
Haptoglobin (mg/dl) 16–199 69
Reticulocytes (%) 0.5–2.5 1.4
d-dimer (ng/ml)   1290
Fibrinogen (mg/dl) 15 0 579
C-reactive protein (mg/liter) 0. .0 98.2
Erythrocyte sedimentation rate (mm/hr)   28
Ferritin (μg/liter) 3 0 181
Iron (μg/dl) 45–160 32
Iron-binding capacity (μg/dl) 23 4 267
Borrelia burgdorferi IgG and IgM antibodies Negative Negative
Parvovirus B19 IgG and IgM antibodies Negative Negative
Epstein–Barr virus viral capsid antigen IgG and IgM 
antibodies
Negative Negative
Epstein–Barr virus viral nuclear antigen IgG antibody Negative Negative
Blood-smear examination for parasites No parasites seen No parasites seen
Anaplasma phagocytophilum DNA Negative Negative
Ehrlichia chaffeensis DNA Negative Negative
E. ewingii and E. canis DNA Negative Negative
E. muris‚Äö√Ñ√¨like DNA Negative Negative",Hairy-cell leukemia.,"An indolent clonal disorder consistent with non-Hodgkin’s lymphoma or hairy-cell leukemia.

Cellulitis with loculated fluid collection in the context of neutropenia.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 39-year-old man was admitted to this hospital because of epistaxis, pain and erythema of the right forearm, and pancytopenia.
The patient had been in his usual state of good health until 6 months before admission, when episodes of spontaneous, prolonged epistaxis developed. Two months before admission, the patient noticed spontaneous bruising of the arms and legs. Four days before admission, pain, swelling, and erythema of the dorsal aspect of the distal right forearm developed, without any preceding trauma; the pain was worse with extension of the fourth and fifth fingers. The same day, fevers, chills, and night sweats developed, along with nausea and frontal headache. The patient took naproxen and acetaminophen, and he had relief of symptoms except for the pain, swelling, and erythema of the right forearm.
The patient presented to an urgent care center for evaluation. The temperature was 36.8[degrees]C, the blood pressure 140/88 mm Hg, the pulse 76 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. There was pain in the dorsal aspect of the distal right forearm, with resistance to extension of the wrist and fourth and fifth fingers. There was a resolving ecchymosis on the left medial proximal calf. Laboratory testing reportedly revealed pancytopenia. Ceftriaxone was administered, and the patient was asked to present to an emergency department for further evaluation.
In the emergency department of this hospital, the patient reported no vision changes, diplopia, dysarthria, numbness, tingling, weakness, cough, dyspnea, abdominal pain, vomiting, diarrhea, or dysuria. There was no fatigue, weight loss, rhinorrhea, pharyngitis, joint stiffness, joint swelling, or myalgias. There was no history of hemarthrosis. Review of previous records revealed that he had had a normal complete blood count approximately 10 years before admission. Six months before admission, the patient had donated blood successfully.
The patient consumed alcohol three times per week; he did not use tobacco or illicit drugs. He lived outside Boston with his wife and two children, all of whom were in good health. He worked for a lighting company and did his own yard work; there was no history of a recent tick bite. He was sexually active with his wife, who worked as a nurse and had sustained a needlestick injury 2 years earlier. He had traveled to Mexico 15 years before admission, Puerto Rico 7 months before admission, Missouri 6 months before admission, Ohio 4 months before admission, and New York 1 month before admission. The patient's father had coronary artery disease, and his paternal grandmother had lung cancer.
On examination, the weight was 95.3 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 30. The patient appeared to be well but was pale. No lymphadenopathy or hepatosplenomegaly was detected. The right forearm was erythematous and mildly swollen, without induration or crepitus; wrist extension was limited by pain in the forearm. There were ecchymoses in the left antecubital fossa. There were no purpura, but scattered petechiae were noted on the palate. The remainder of the physical examination was normal.
Blood levels of electrolytes, glucose, calcium, magnesium, phosphorus, folate, vitamin B12, methylmalonic acid, uric acid, creatine kinase, and thyrotropin were normal, as were results of tests of kidney and liver function. A direct antiglobulin test was negative. Urinalysis was normal. An assay for antinuclear antibodies was positive at a titer of 1:40 with a speckled pattern, and an assay for rheumatoid factor antibodies was negative. Screening tests were negative for human immunodeficiency virus (HIV) type 1 p24 antigen and HIV type 1 and type 2 antibodies, hepatitis B virus surface antigen, hepatitis B virus core IgM antibodies, and hepatitis C virus antibodies. Cytomegalovirus DNA viral load was not detected. Tests for histoplasma antigen in urine and for heterophile antibodies were negative, as was an interferon-gamma release assay for Mycobacterium tuberculosis. Other laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
Dr. F. Joseph Simeone: Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of oral and intravenous contrast material, revealed enlarged subcarinal, right hilar, and diaphragmatic pericaval lymph nodes (Figure 1A). The spleen measured 18.3 cm in the maximum dimension (normal value, <=12 cm), and there was evidence of retroperitoneal lymphadenopathy, including a portacaval lymph node measuring 3.2 cm in diameter, an aortocaval lymph node measuring 1.2 cm in diameter, and a superior pancreatic lymph node measuring 2.9 cm in diameter (Figure 1B). CT of the right humerus and forearm, performed after the administration of intravenous contrast material, revealed a rim-enhancing fluid collection, measuring 3.1 cm in the maximum dimension, in the extensor compartment of the mid-forearm (Figure 1C), with overlying skin thickening and subcutaneous edema along the dorsal forearm and without evidence of acute fracture or dislocation.	
Figure 1 
Dr. Balinda: The patient was admitted to the hospital, and ceftriaxone was continued.
Dr. Simeone: On the day after admission, the fluid collection in the right forearm was aspirated with the use of ultrasonographic guidance (Figure 1D). The fluid was sent to the microbiology laboratory for evaluation.
Dr. Balinda: The hematology service was consulted. Examination of a peripheral-blood smear revealed evidence of anisocytosis, hypochromia, and a few large platelets and no evidence of blasts or hemolysis. Blood cultures showed no growth. A diagnostic procedure was performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 39-year-old man was admitted to this hospital because of epistaxis, pain and erythema of the right forearm, and pancytopenia.
The patient had been in his usual state of good health until 6 months before admission, when episodes of spontaneous, prolonged epistaxis developed. Two months before admission, the patient noticed spontaneous bruising of the arms and legs. Four days before admission, pain, swelling, and erythema of the dorsal aspect of the distal right forearm developed, without any preceding trauma; the pain was worse with extension of the fourth and fifth fingers. The same day, fevers, chills, and night sweats developed, along with nausea and frontal headache. The patient took naproxen and acetaminophen, and he had relief of symptoms except for the pain, swelling, and erythema of the right forearm.
The patient presented to an urgent care center for evaluation. The temperature was 36.8[degrees]C, the blood pressure 140/88 mm Hg, the pulse 76 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. There was pain in the dorsal aspect of the distal right forearm, with resistance to extension of the wrist and fourth and fifth fingers. There was a resolving ecchymosis on the left medial proximal calf. Laboratory testing reportedly revealed pancytopenia. Ceftriaxone was administered, and the patient was asked to present to an emergency department for further evaluation.
In the emergency department of this hospital, the patient reported no vision changes, diplopia, dysarthria, numbness, tingling, weakness, cough, dyspnea, abdominal pain, vomiting, diarrhea, or dysuria. There was no fatigue, weight loss, rhinorrhea, pharyngitis, joint stiffness, joint swelling, or myalgias. There was no history of hemarthrosis. Review of previous records revealed that he had had a normal complete blood count approximately 10 years before admission. Six months before admission, the patient had donated blood successfully.
The patient consumed alcohol three times per week; he did not use tobacco or illicit drugs. He lived outside Boston with his wife and two children, all of whom were in good health. He worked for a lighting company and did his own yard work; there was no history of a recent tick bite. He was sexually active with his wife, who worked as a nurse and had sustained a needlestick injury 2 years earlier. He had traveled to Mexico 15 years before admission, Puerto Rico 7 months before admission, Missouri 6 months before admission, Ohio 4 months before admission, and New York 1 month before admission. The patient's father had coronary artery disease, and his paternal grandmother had lung cancer.
On examination, the weight was 95.3 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 30. The patient appeared to be well but was pale. No lymphadenopathy or hepatosplenomegaly was detected. The right forearm was erythematous and mildly swollen, without induration or crepitus; wrist extension was limited by pain in the forearm. There were ecchymoses in the left antecubital fossa. There were no purpura, but scattered petechiae were noted on the palate. The remainder of the physical examination was normal.
Blood levels of electrolytes, glucose, calcium, magnesium, phosphorus, folate, vitamin B12, methylmalonic acid, uric acid, creatine kinase, and thyrotropin were normal, as were results of tests of kidney and liver function. A direct antiglobulin test was negative. Urinalysis was normal. An assay for antinuclear antibodies was positive at a titer of 1:40 with a speckled pattern, and an assay for rheumatoid factor antibodies was negative. Screening tests were negative for human immunodeficiency virus (HIV) type 1 p24 antigen and HIV type 1 and type 2 antibodies, hepatitis B virus surface antigen, hepatitis B virus core IgM antibodies, and hepatitis C virus antibodies. Cytomegalovirus DNA viral load was not detected. Tests for histoplasma antigen in urine and for heterophile antibodies were negative, as was an interferon-gamma release assay for Mycobacterium tuberculosis. Other laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
Dr. F. Joseph Simeone: Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the administration of oral and intravenous contrast material, revealed enlarged subcarinal, right hilar, and diaphragmatic pericaval lymph nodes (Figure 1A). The spleen measured 18.3 cm in the maximum dimension (normal value, <=12 cm), and there was evidence of retroperitoneal lymphadenopathy, including a portacaval lymph node measuring 3.2 cm in diameter, an aortocaval lymph node measuring 1.2 cm in diameter, and a superior pancreatic lymph node measuring 2.9 cm in diameter (Figure 1B). CT of the right humerus and forearm, performed after the administration of intravenous contrast material, revealed a rim-enhancing fluid collection, measuring 3.1 cm in the maximum dimension, in the extensor compartment of the mid-forearm (Figure 1C), with overlying skin thickening and subcutaneous edema along the dorsal forearm and without evidence of acute fracture or dislocation.	
Figure 1 
Dr. Balinda: The patient was admitted to the hospital, and ceftriaxone was continued.
Dr. Simeone: On the day after admission, the fluid collection in the right forearm was aspirated with the use of ultrasonographic guidance (Figure 1D). The fluid was sent to the microbiology laboratory for evaluation.
Dr. Balinda: The hematology service was consulted. Examination of a peripheral-blood smear revealed evidence of anisocytosis, hypochromia, and a few large platelets and no evidence of blasts or hemolysis. Blood cultures showed no growth. A diagnostic procedure was performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with spontaneous, prolonged epistaxis, spontaneous bruising, pain, swelling, and erythema of the forearm, and pancytopenia. The patient's symptoms and the presence of pancytopenia suggest a hematological disorder. The patient's CT scan revealed enlarged lymph nodes and an enlarged spleen, which are common in lymphomas and leukemias. The absence of blasts in the peripheral blood smear makes acute leukemia less likely. The patient's symptoms, along with the imaging findings, are suggestive of a lymphoproliferative disorder such as lymphoma. \n\nDiagnosis: Lymphoma""
      },
      ""finish_reason"": ""stop""
    }
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  ""usage"": {
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}",Lymphoma,N,"{
  ""id"": ""chatcmpl-7i2zJG2iJJiC6OtPCaEE94g0ma2gj"",
  ""object"": ""chat.completion"",
  ""created"": 1690732273,
  ""model"": ""gpt-4-0613"",
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    {
      ""index"": 0,
      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient is a 39-year-old man presenting with spontaneous, prolonged epistaxis, spontaneous bruising, pain, swelling, and erythema of the right forearm, and pancytopenia. The differential diagnosis for this patient includes hematologic malignancies such as leukemia or lymphoma, aplastic anemia, myelodysplastic syndrome, and systemic lupus erythematosus (SLE). The patient's history of spontaneous bleeding and bruising, along with pancytopenia, suggests a hematologic disorder. The absence of blasts on peripheral blood smear makes leukemia less likely. The patient's positive antinuclear antibody (ANA) test could suggest SLE, but the patient lacks other common symptoms of SLE such as joint pain, fatigue, and rash. The patient's CT scan shows enlarged lymph nodes and an enlarged spleen, which could suggest lymphoma. However, the patient lacks common symptoms of lymphoma such as weight loss and fatigue. The patient's symptoms, along with the findings of pancytopenia and an enlarged spleen, are most consistent with aplastic anemia. \n\nDiagnosis: Aplastic anemia.""
      },
      ""finish_reason"": ""stop""
    }
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}",Aplastic anemia,N
10.1056/NEJMcpc1802824,Case 27-2018: A 3-Year-Old Boy with Seizures,"Hemoglobin (g/dl) 11.9 10. .5 10.8
Hematocrit (%)  33.5 33. .0 31.2
White-cell count (per mm3) 15,030   7460
Differential count (%)
Neutrophils 59.1  66.7
Immature granulocytes 0.0–0.8 0.3  0.4
Lymphocytes 34.4 27.0–60.0 26.9
Monocytes   5.3  5.4
Eosinophils   0.4 0. .0 0.1
Basophils   0.5  0.5
Sodium (mmol/liter)   137   142
Potassium (mmol/liter)   4.8 3.4–4.7 3.8
Chloride (mmol/liter)   96 98–115 101
Carbon dioxide (mmol/liter)   24 2 8 20
Anion gap (mmol/liter)   17   21
Phosphorus (mg/dl)†  5.6 3.7
Borrelia burgdorferi IgG and IgM 
antibody screen
Negative Negative                                                                                                           Cerebrospinal Fluid Analysis                                                                                       Color Colorless
Turbidity Clear
Xanthochromia None
Red-cell count (per mm3)
Tube 1 0–5 46
Tube 4 0–5 9
White-cell count (per mm3)
Tube 1 0–5 38
Tube 4 0–5 33
Differential count (%)
Tube 1 72% lymphocytes, 4% reactive lymphocytes, 
24% monocytes
Tube 4 67% lymphocytes, 5% reactive lymphocytes, 
23% monocytes, 5% macrophages
Protein (mg/dl)  29
Glucose (mg/dl)†  68
Gram’s stain Abundant mononuclear cells, no polymor‑
phonuclear cells, no organisms seen",Anti–N-methyl-d-aspartate (NMDA) receptor encephalitis.,Anti–N-methyl-d-aspartate (NMDA) receptor encephalitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 3-year-old boy was admitted to this hospital during the summer because of a seizure.
The patient had been well until 3 days before admission, when one episode of emesis occurred. The following evening, he was fussy, and on the third day of illness, he had decreased language output and one loose bowel movement. That evening, he told his mother that he wanted to sleep, which was atypical behavior. One minute after the patient lay down, he suddenly sat up; his whole body stiffened, and he did not respond to his name being called. His mother noted that he felt warm to the touch, that his head was turned to the left, and that he appeared to be ""staring off into space."" Both arms were flexed, and there were shaking movements of the arms and legs that were greater on the left side than on the right side. After 1 minute, the movements stopped and the patient vomited; he seemed to be confused and then fell asleep. Emergency medical services were called. On examination 10 minutes later, he was somnolent but arousable and had spontaneous movements of the arms and legs. He vomited again and was transported to the emergency department of another hospital, arriving 25 minutes after the episode.
On examination, the patient was alert, active, and in no apparent distress. The temperature was 36.9[degrees]C; other vital signs were normal. The weight was 15.8 kg (71st percentile). Strength, sensation, coordination, and cranial-nerve function were normal, as was the remainder of the physical examination. The blood glucose level, obtained by fingerstick testing, was 105 mg per deciliter (5.8 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). The patient vomited, and ondansetron was administered orally. Early the following morning, after a pediatric neurologist was consulted, the patient was transferred to the emergency department of this hospital.
The history was obtained from the patient's mother. There had been no known head trauma or toxic ingestion. The patient had been born after a full-term gestation and had had normal growth and development, except for a previous mild speech delay; he currently knew at least 200 words and spoke in full sentences. He had not received vaccines for Streptococcus pneumoniae, Haemophilus influenzae type b, hepatitis B virus, or rotavirus because of parental refusal; he had received other routine childhood vaccines. He did not take any medications or have any known allergies. He lived with his parents and siblings in an urban area of New England. There were no pets at home. There was no family history of seizures.
On examination, the patient was sleeping; he awoke when touched and pushed the examiner away. The temperature was 37.4[degrees]C, the pulse 86 beats per minute, the blood pressure 100/59 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. The pupils were round, equal, and reactive to light, decreasing from 3 mm to 2 mm in diameter; there was no ptosis. The face was symmetric, with normal forehead wrinkling, blinking, smiling, and cheek puffing. Muscle bulk and tone were normal, as was strength. The patient withdrew from tickling. Deep-tendon reflexes were 1+ throughout, and plantar reflexes were flexor. The remainder of the examination was normal. The red-cell count, red-cell indexes, platelet count, and results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, and magnesium; other laboratory test results are shown in Table 1.	
Table 1 
Magnetic resonance imaging (MRI) of the head was performed, and a T2-weighted single-shot turbo spin-echo image showed normal ventricles and no extraaxial fluid collection, mass lesion, or midline shift. Electroencephalography (EEG), performed 12 hours after the seizure, revealed continuous focal polymorphic delta slowing and occasional broad sharp wave discharges over the right frontal region. That afternoon, the patient's temperature was 38.2[degrees]C; acetaminophen was administered. He was observed overnight and had no seizure activity, and the following morning, he was discharged home.
One week after discharge, the patient was taken back to the emergency department of the other hospital. His mother reported that he had been well for the 2 days after discharge, but for the past 5 days, he had had progressively decreased language output, increased sleep (such that he was now sleeping for most of the day, awakening for only 10 minutes at a time), decreased oral intake, and constipation that could not be relieved by orally administered polyethylene glycol. During the past 2 days, mood lability had developed; there had been periods when he seemed enraged and was physically and verbally aggressive toward family members, as well as periods when he laughed hysterically, and these moods had not been provoked. He had babbled, repeated unusual phrases, and lost interest in games, toys, and videos; his gait had become increasingly unsteady, with frequent tripping. On the day of this presentation, writhing movements had occurred after he ate and drank; his mother thought these movements might have been caused by abdominal pain. In addition, his urine output had decreased.
On examination, the patient was quiet, with a flat affect and subdued behavior. Vital signs were normal; the weight was 14.7 kg (48th percentile). The oral mucous membranes were dry. The abdomen was soft and flat, without tenderness; bowel sounds were normal. The patient followed some commands and then fell asleep during the examination. The remainder of the examination was normal. The blood glucose level, obtained by fingerstick testing, was 76 mg per deciliter (4.2 mmol per liter), and abdominal radiography revealed feces in the colon, without evidence of obstruction. Normal saline was administered intravenously; 1 hour later, the red-cell count, red-cell indexes, platelet count, results of renal- and liver-function tests, and venous blood gas measurements were normal, as were blood levels of glucose, calcium, magnesium, thyrotropin, and free thyroxine. A serum toxicology screen was negative; other laboratory test results are shown in Table 1. Abdominal ultrasonography revealed increased bowel gas, without evidence of intussusception. The patient was transferred to the emergency department of this hospital for further evaluation and treatment.
In the emergency department, the patient was somnolent but aroused in response to voice; he made only limited eye contact with his parents and the examiner and had unintelligible speech. There was one unprovoked episode of agitation and screaming. Vital signs were normal. The pupils were round, equal, and reactive to light, decreasing from 5 mm to 2 mm in diameter. He blinked in response to threat bilaterally. Extraocular movements were intact, without nystagmus. The face was symmetric, and the tongue was midline. The neck was supple. The patient moved the arms and legs equally and had normal strength and normal sensation to light touch. Deep-tendon reflexes were 2+ throughout. Plantar reflexes were flexor. The gait was unsteady and ataxic. The remainder of the examination was normal. A sodium phosphate-based enema was administered, and the patient had a large bowel movement. He was admitted to the hospital for further evaluation and treatment.
The following day, magnetic resonance angiography of the head was normal. MRI of the head and spine was performed before and after the intravenous administration of contrast material, and fluid-attenuated inversion recovery (FLAIR) images revealed a small number of scattered, punctate, nonspecific hyperintense foci in the white matter of the brain and mild, scattered mucosal thickening in the paranasal sinus, without other abnormalities. A lumbar puncture was performed; the results of cerebrospinal fluid (CSF) analysis are shown in Table 2. A plasma sample was sent for acylcarnitine profile analysis, and tests of a nasopharyngeal swab for adenovirus, parainfluenza virus, and metapneumovirus antigens were negative. Urinalysis revealed a specific gravity of 1.017, a pH of 6.0, and 1+ ketones. Intravenous fluids, acyclovir, and oral acetaminophen and ibuprofen were administered.	
Table 2 
During the third and fourth hospital days, the patient had episodes of irritability, thrashing, and screaming, as well as intermittent stereotyped arm movements, athetoid hand movements, and orofacial dyskinesias. Video EEG revealed generalized polymorphic slowing of the resting background (at a rate of 2 to 5 Hz), even while the patient was in a maximally awake state; the abnormal movements had no correlate on EEG. On the morning of the fifth hospital day, apnea occurred, with associated tachycardia, hypertension, opisthotonic posturing, and jaw clenching. Ventilation with a bag-valve-mask device was difficult to administer. Midazolam, fentanyl, and rocuronium were administered intravenously, the trachea was intubated, and mechanical ventilation was begun; thereafter, the posturing resolved and vital signs normalized. The patient was transferred to the pediatric intensive care unit (ICU).
A diagnosis and management decisions were made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 3-year-old boy was admitted to this hospital during the summer because of a seizure.
The patient had been well until 3 days before admission, when one episode of emesis occurred. The following evening, he was fussy, and on the third day of illness, he had decreased language output and one loose bowel movement. That evening, he told his mother that he wanted to sleep, which was atypical behavior. One minute after the patient lay down, he suddenly sat up; his whole body stiffened, and he did not respond to his name being called. His mother noted that he felt warm to the touch, that his head was turned to the left, and that he appeared to be ""staring off into space."" Both arms were flexed, and there were shaking movements of the arms and legs that were greater on the left side than on the right side. After 1 minute, the movements stopped and the patient vomited; he seemed to be confused and then fell asleep. Emergency medical services were called. On examination 10 minutes later, he was somnolent but arousable and had spontaneous movements of the arms and legs. He vomited again and was transported to the emergency department of another hospital, arriving 25 minutes after the episode.
On examination, the patient was alert, active, and in no apparent distress. The temperature was 36.9[degrees]C; other vital signs were normal. The weight was 15.8 kg (71st percentile). Strength, sensation, coordination, and cranial-nerve function were normal, as was the remainder of the physical examination. The blood glucose level, obtained by fingerstick testing, was 105 mg per deciliter (5.8 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). The patient vomited, and ondansetron was administered orally. Early the following morning, after a pediatric neurologist was consulted, the patient was transferred to the emergency department of this hospital.
The history was obtained from the patient's mother. There had been no known head trauma or toxic ingestion. The patient had been born after a full-term gestation and had had normal growth and development, except for a previous mild speech delay; he currently knew at least 200 words and spoke in full sentences. He had not received vaccines for Streptococcus pneumoniae, Haemophilus influenzae type b, hepatitis B virus, or rotavirus because of parental refusal; he had received other routine childhood vaccines. He did not take any medications or have any known allergies. He lived with his parents and siblings in an urban area of New England. There were no pets at home. There was no family history of seizures.
On examination, the patient was sleeping; he awoke when touched and pushed the examiner away. The temperature was 37.4[degrees]C, the pulse 86 beats per minute, the blood pressure 100/59 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. The pupils were round, equal, and reactive to light, decreasing from 3 mm to 2 mm in diameter; there was no ptosis. The face was symmetric, with normal forehead wrinkling, blinking, smiling, and cheek puffing. Muscle bulk and tone were normal, as was strength. The patient withdrew from tickling. Deep-tendon reflexes were 1+ throughout, and plantar reflexes were flexor. The remainder of the examination was normal. The red-cell count, red-cell indexes, platelet count, and results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, and magnesium; other laboratory test results are shown in Table 1.	
Table 1 
Magnetic resonance imaging (MRI) of the head was performed, and a T2-weighted single-shot turbo spin-echo image showed normal ventricles and no extraaxial fluid collection, mass lesion, or midline shift. Electroencephalography (EEG), performed 12 hours after the seizure, revealed continuous focal polymorphic delta slowing and occasional broad sharp wave discharges over the right frontal region. That afternoon, the patient's temperature was 38.2[degrees]C; acetaminophen was administered. He was observed overnight and had no seizure activity, and the following morning, he was discharged home.
One week after discharge, the patient was taken back to the emergency department of the other hospital. His mother reported that he had been well for the 2 days after discharge, but for the past 5 days, he had had progressively decreased language output, increased sleep (such that he was now sleeping for most of the day, awakening for only 10 minutes at a time), decreased oral intake, and constipation that could not be relieved by orally administered polyethylene glycol. During the past 2 days, mood lability had developed; there had been periods when he seemed enraged and was physically and verbally aggressive toward family members, as well as periods when he laughed hysterically, and these moods had not been provoked. He had babbled, repeated unusual phrases, and lost interest in games, toys, and videos; his gait had become increasingly unsteady, with frequent tripping. On the day of this presentation, writhing movements had occurred after he ate and drank; his mother thought these movements might have been caused by abdominal pain. In addition, his urine output had decreased.
On examination, the patient was quiet, with a flat affect and subdued behavior. Vital signs were normal; the weight was 14.7 kg (48th percentile). The oral mucous membranes were dry. The abdomen was soft and flat, without tenderness; bowel sounds were normal. The patient followed some commands and then fell asleep during the examination. The remainder of the examination was normal. The blood glucose level, obtained by fingerstick testing, was 76 mg per deciliter (4.2 mmol per liter), and abdominal radiography revealed feces in the colon, without evidence of obstruction. Normal saline was administered intravenously; 1 hour later, the red-cell count, red-cell indexes, platelet count, results of renal- and liver-function tests, and venous blood gas measurements were normal, as were blood levels of glucose, calcium, magnesium, thyrotropin, and free thyroxine. A serum toxicology screen was negative; other laboratory test results are shown in Table 1. Abdominal ultrasonography revealed increased bowel gas, without evidence of intussusception. The patient was transferred to the emergency department of this hospital for further evaluation and treatment.
In the emergency department, the patient was somnolent but aroused in response to voice; he made only limited eye contact with his parents and the examiner and had unintelligible speech. There was one unprovoked episode of agitation and screaming. Vital signs were normal. The pupils were round, equal, and reactive to light, decreasing from 5 mm to 2 mm in diameter. He blinked in response to threat bilaterally. Extraocular movements were intact, without nystagmus. The face was symmetric, and the tongue was midline. The neck was supple. The patient moved the arms and legs equally and had normal strength and normal sensation to light touch. Deep-tendon reflexes were 2+ throughout. Plantar reflexes were flexor. The gait was unsteady and ataxic. The remainder of the examination was normal. A sodium phosphate-based enema was administered, and the patient had a large bowel movement. He was admitted to the hospital for further evaluation and treatment.
The following day, magnetic resonance angiography of the head was normal. MRI of the head and spine was performed before and after the intravenous administration of contrast material, and fluid-attenuated inversion recovery (FLAIR) images revealed a small number of scattered, punctate, nonspecific hyperintense foci in the white matter of the brain and mild, scattered mucosal thickening in the paranasal sinus, without other abnormalities. A lumbar puncture was performed; the results of cerebrospinal fluid (CSF) analysis are shown in Table 2. A plasma sample was sent for acylcarnitine profile analysis, and tests of a nasopharyngeal swab for adenovirus, parainfluenza virus, and metapneumovirus antigens were negative. Urinalysis revealed a specific gravity of 1.017, a pH of 6.0, and 1+ ketones. Intravenous fluids, acyclovir, and oral acetaminophen and ibuprofen were administered.	
Table 2 
During the third and fourth hospital days, the patient had episodes of irritability, thrashing, and screaming, as well as intermittent stereotyped arm movements, athetoid hand movements, and orofacial dyskinesias. Video EEG revealed generalized polymorphic slowing of the resting background (at a rate of 2 to 5 Hz), even while the patient was in a maximally awake state; the abnormal movements had no correlate on EEG. On the morning of the fifth hospital day, apnea occurred, with associated tachycardia, hypertension, opisthotonic posturing, and jaw clenching. Ventilation with a bag-valve-mask device was difficult to administer. Midazolam, fentanyl, and rocuronium were administered intravenously, the trachea was intubated, and mechanical ventilation was begun; thereafter, the posturing resolved and vital signs normalized. The patient was transferred to the pediatric intensive care unit (ICU).
A diagnosis and management decisions were made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Anti-NMDA receptor encephalitis. The patient's symptoms of decreased language output, increased sleep, mood lability, unsteady gait, and writhing movements, along with the results of the MRI and EEG, are consistent with this condition. Anti-NMDA receptor encephalitis is a type of inflammation of the brain that is often associated with tumors, but can also occur without a known cause. It is characterized by a variety of neurological and psychiatric symptoms, including seizures, movement disorders, and changes in behavior, mood, and personality. The condition is diagnosed through the detection of antibodies against the NMDA receptor in the cerebrospinal fluid.""
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        ""content"": ""This is a 3-year-old boy who presents with a seizure, decreased language output, increased sleep, decreased oral intake, constipation, mood lability, unsteady gait, and decreased urine output. The differential diagnosis for this patient includes meningitis, encephalitis, brain tumor, and anti-NMDA receptor encephalitis. The patient's MRI of the head was normal, making a brain tumor less likely. The patient's cerebrospinal fluid analysis showed no evidence of infection, making meningitis and encephalitis less likely. The constellation of symptoms including seizure, mood lability, decreased language output, and unsteady gait is concerning for anti-NMDA receptor encephalitis. Furthermore, the patient's symptoms worsened over time and he required intubation and mechanical ventilation, which is consistent with the progression of anti-NMDA receptor encephalitis.\n\nDiagnosis: Anti-NMDA receptor encephalitis is the most likely diagnosis.""
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10.1056/NEJMcpc1807494,"Case 26-2018: A 48-Year-Old Man with Fever, Chills, Myalgias, and Rash","Hemoglobin (g/dl)   12.2   10.4 10.0
Hematocrit (%)   35.2   30.2 29.9
Red-cell count (per mm3) 4,200,000–
5,400,000
3,910,000 3,360,000 3,100,000
White-cell count (per mm3
) 18,300   11,000 6500
Differential count (%)
Neutrophils  24.0   44 45
Lymphocytes 40.3   24 29
Atypical lymphocytes 0 4 0 4 13
Monocytes 2.0–12.0 10.6   2 5
Eosinophils 0–4 24   23 8
Bands 0–10 3 0
Platelet count (per mm3
)   90,000   111,000 107,000
Mean platelet volume (fl) 7. .0 12.7 8.4–12.0
Sodium (mmol/liter)   133   129 135
Potassium (mmol/liter)  3.2   4.0 3.5
Chloride (mmol/liter)  96   95 101
Carbon dioxide (mmol/liter)  26   22 23.7
Urea nitrogen (mg/dl) 6–23 15   17 17
Creatinine (mg/dl) 0.5–1.4 1.2   0.99 1.04
Glucose (mg/dl) 6 9 92   158 104
Calcium (mg/dl)  8.1   8.0 7.8
Total protein (g/dl) 8.3 6. .3 7.5 5.8
Albumin (g/dl)   2.3   2.6 2.2
Globulin (g/dl)  4.9 3.8
Total bilirubin (mg/dl)  0.5  0.5 0.5
Aspartate aminotransferase (U/liter)   95   99 188
Alanine aminotransferase (U/liter)  153 10.55 116 160
Alkaline phosphatase (U/liter) 3 0 811   641 498
Erythrocyte sedimentation rate (mm/hr)   74  
C-reactive protein (mg/liter)  41.33  
Lactate dehydrogenase (U/liter) 725 11 10 490
γ-Glutamyltransferase (U/liter) 286
C3 (mg/dl)  105
C4 (mg/dl)  15
Cryoprotein None present None present
Heterophile antibody Negative Weakly positive
EBV IgM antibody to viral capsid antigen Negative Negative
EBV IgG antibody to viral capsid antigen Negative Positive
EBV IgG antibody to nuclear antigen Negative Positive                                          Cytomegalovirus antigenemia assay Negative Negative
Antitreponemal antibody Negative Negative
HIV-1 and HIV-2 antibody and HIV-1 p24 
antigen
Negative Negative
HIV-1 on PCR assay Not detected Not detected
Hepatitis A virus total antibody Negative Negative
Hepatitis A virus IgM antibody Negative Negative
Hepatitis B virus surface antigen Negative Negative
Hepatitis B virus surface antibody,
 qualitative
Negative Negative
Hepatitis B virus core antibody Negative Negative
Hepatitis C virus antibody Negative Negative
Tryptase (ng/ml) 14.5
Antinuclear antibody Negative at 1:40 
and 1:160
Positive at 1:40 
and 1:160, 
speckled
Urine
Color Yellow Yellow Yellow
pH 6.0   5.5
Specific gravity 1.025   1.008
Glucose Negative Negative Negative
Ketones Negative Negative Negative
Protein Trace Negative Negative
Leukocytes Negative Negative Negative
Blood Negative Negative Negative","The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, associated with human herpesvirus 6 infection or reactivation",The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old man was evaluated at this hospital because of fever, chills, myalgias, diarrhea, and a diffuse rash.
The patient had been in his usual state of good health until about 3 weeks before admission, in the late spring, when he noted the onset of fevers, chills, headache, and diffuse myalgias. He thought that he had influenza. Five days later, he noted an erythematous rash affecting his trunk, legs, feet, and hands. One day after that, mild, diffuse abdominal discomfort developed, along with anorexia and multiple episodes of nonbloody diarrhea. During the next 5 days, he had positional dizziness with syncope. Fourteen days before admission to this hospital, the patient sought medical attention at another hospital.
At the other hospital, examination revealed that the patient had fatigue and a diffuse erythematous rash. The temperature was 37.7[degrees]C. Laboratory evaluation was notable for an absolute eosinophil count of 600 per cubic millimeter (reference range at the other hospital, 0 to 200) and elevated levels on liver-function tests. Computed tomography (CT) of the chest, performed without the intravenous administration of contrast material, reportedly revealed mild, diffuse enlargement of lymph nodes, which were up to 9 mm in diameter in the mediastinum and up to 15 mm in diameter in the porta hepatis. A test of a nasopharyngeal swab for influenza A and B viruses, a rapid test of a throat swab for streptococcal antigen, and tests of the blood for babesia DNA, ehrlichia DNA, hepatitis A virus antibody, hepatitis B virus surface antibody and surface antigen, hepatitis C virus antibody, human immunodeficiency virus (HIV) p24 antigen and antibody, and Lyme disease IgM antibody were negative. The patient was treated with an unknown antibiotic agent, and after 5 days, he was discharged with prescriptions for cetirizine and hydroxyzine. He was scheduled for follow-up with his primary care physician.
The day before admission, the patient observed new mild swelling of the face and hands, with blisters on the palms. He was seen by his primary care physician the next day, and he reported persistent fevers, chills, rash with blistering, anorexia, and positional light-headedness. Laboratory test results are shown in Table 1. On the basis of advice from a rheumatologist located in the same office, the patient was given one dose of oral prednisone and was referred to the emergency department of this hospital.	
Table 1
Additional history was obtained in the emergency department. The patient reported pruritus in the areas of the previous leg rash, fatigue, chronic pain in the cervical spine and low back, and a mostly intentional weight loss of 11 kg over the previous 15 weeks. He had had no known exposures to animals or insects. He had a history of hyperlipidemia, depression, and gastroesophageal reflux disease. Medications included aspirin, mirtazapine, rosuvastatin, omeprazole, and cetirizine, as well as hydroxyzine as needed for pruritus. He reported that he had started to take a new over-the-counter medication for the treatment of pain approximately 5 weeks before admission but had stopped taking it at the onset of his presenting symptoms. He could not recall the name of this new medication. He had had no adverse reactions to medications. His family history was notable for lung cancer in his mother and diabetes and coronary artery disease in his father; there was no history of autoimmune or dermatologic disorders. He had smoked two packs of cigarettes daily and marijuana once weekly for the past 30 years. He did not drink alcohol or use illicit drugs. He worked as a manual laborer and driver. He had not traveled outside of New England. He was single and had had multiple female sexual contacts but had always used barrier protection; the young grandchild of his current sexual partner had recently had a self-limited febrile illness with a diffuse maculopapular, erythematous rash.
On examination, the patient appeared fatigued. The temperature was 37.1[degrees]C, the heart rate 89 beats per minute, the blood pressure 132/57 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. The weight was 79 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 28.1. He had mild periorbital edema and mild exfoliative scale on the temple and forehead. A blanching, maculopapular rash was present on the trunk. On the arms, legs, and dorsal feet, there were thin, faintly violaceous plaques with mild exfoliative scale. Small flaccid bullae, including some that were hemorrhagic, were noted on several fingers and the palms, and a few had ruptured (Figure 1). He did not have a rash on mucosal surfaces or nail changes. There were mildly tender, mobile lymph nodes in the bilateral cervical, submandibular, axillary, and inguinal distributions, including a 1-cm axillary node and a 2-cm inguinal node. There was mild abdominal tenderness in the upper quadrants, with hepatosplenomegaly. The stool was guaiac-negative. The remainder of the examination was normal.	
Figure 1 
Blood levels of thyrotropin, creatine kinase, troponin T, amylase, lipase, and vitamin D were normal, as were the serum osmolality, basophil count, prothrombin time, and activated partial-thromboplastin time. Other laboratory test results are shown in Table 1.
The patient was admitted to the general medicine unit. Two sets of blood cultures were obtained. Examination of a peripheral-blood smear revealed atypical-appearing mononuclear cells.
Dr. Shaunagh McDermott: On the second hospital day, CT of the chest, abdomen, and pelvis was performed after the intravenous administration of contrast material. There were areas of centrilobular emphysema and bronchial-wall thickening, scattered pulmonary nodules (2 to 3 mm in diameter) in the upper lobes, and multiple enlarged lymph nodes (Figure 2A and 2B). There was also splenomegaly (spleen length, 15.2 cm; normal length, <=12.0 cm), with a splenic cyst (Figure 2B).	
Figure 2 
Dr. Tsiaras: On the third hospital day, the temperature rose to 38.4[degrees]C and the heart rate was 110 beats per minute. Laboratory test results are shown in Table 1. Cultures of the urine and blood were obtained. Serum protein electrophoresis revealed mild, diffuse hypergammaglobulinemia, with a level of IgG lambda M component in the gamma region of 0.07 g per deciliter. Levels of serum free kappa and lambda light chains were normal. Additional imaging studies were obtained.
Dr. McDermott: Ultrasonography of the legs and arms was negative for venous thrombosis; however, enlarged lymph nodes were noted incidentally (Figure 2C). CT with positron-emission tomography (PET) was performed on the sixth hospital day. There were multiple lymph nodes with 18F-fluorodeoxyglucose (FDG) avidity in the axillary, cervical, supraclavicular, paratracheal, hilar, subcarinal, portal, iliac, and inguinal distributions, and there was diffuse increase in FDG uptake in the spleen (Figure 2D).
Dr. George Eng: Flow cytometry of a peripheral-blood specimen was negative for a monotypic B-cell population and for T cells with immunophenotypic abnormalities. Biopsy of an enlarged right inguinal lymph node was performed on the seventh hospital day; histopathological examination of the biopsy specimen revealed florid paracortical hyperplasia, without evidence of cancer (Figure 3). Flow cytometry of the biopsy specimen was negative for cancer.	
Figure 3 
Dr. Tsiaras: Diagnostic test results were received
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 48-year-old man was evaluated at this hospital because of fever, chills, myalgias, diarrhea, and a diffuse rash.
The patient had been in his usual state of good health until about 3 weeks before admission, in the late spring, when he noted the onset of fevers, chills, headache, and diffuse myalgias. He thought that he had influenza. Five days later, he noted an erythematous rash affecting his trunk, legs, feet, and hands. One day after that, mild, diffuse abdominal discomfort developed, along with anorexia and multiple episodes of nonbloody diarrhea. During the next 5 days, he had positional dizziness with syncope. Fourteen days before admission to this hospital, the patient sought medical attention at another hospital.
At the other hospital, examination revealed that the patient had fatigue and a diffuse erythematous rash. The temperature was 37.7[degrees]C. Laboratory evaluation was notable for an absolute eosinophil count of 600 per cubic millimeter (reference range at the other hospital, 0 to 200) and elevated levels on liver-function tests. Computed tomography (CT) of the chest, performed without the intravenous administration of contrast material, reportedly revealed mild, diffuse enlargement of lymph nodes, which were up to 9 mm in diameter in the mediastinum and up to 15 mm in diameter in the porta hepatis. A test of a nasopharyngeal swab for influenza A and B viruses, a rapid test of a throat swab for streptococcal antigen, and tests of the blood for babesia DNA, ehrlichia DNA, hepatitis A virus antibody, hepatitis B virus surface antibody and surface antigen, hepatitis C virus antibody, human immunodeficiency virus (HIV) p24 antigen and antibody, and Lyme disease IgM antibody were negative. The patient was treated with an unknown antibiotic agent, and after 5 days, he was discharged with prescriptions for cetirizine and hydroxyzine. He was scheduled for follow-up with his primary care physician.
The day before admission, the patient observed new mild swelling of the face and hands, with blisters on the palms. He was seen by his primary care physician the next day, and he reported persistent fevers, chills, rash with blistering, anorexia, and positional light-headedness. Laboratory test results are shown in Table 1. On the basis of advice from a rheumatologist located in the same office, the patient was given one dose of oral prednisone and was referred to the emergency department of this hospital.	
Table 1
Additional history was obtained in the emergency department. The patient reported pruritus in the areas of the previous leg rash, fatigue, chronic pain in the cervical spine and low back, and a mostly intentional weight loss of 11 kg over the previous 15 weeks. He had had no known exposures to animals or insects. He had a history of hyperlipidemia, depression, and gastroesophageal reflux disease. Medications included aspirin, mirtazapine, rosuvastatin, omeprazole, and cetirizine, as well as hydroxyzine as needed for pruritus. He reported that he had started to take a new over-the-counter medication for the treatment of pain approximately 5 weeks before admission but had stopped taking it at the onset of his presenting symptoms. He could not recall the name of this new medication. He had had no adverse reactions to medications. His family history was notable for lung cancer in his mother and diabetes and coronary artery disease in his father; there was no history of autoimmune or dermatologic disorders. He had smoked two packs of cigarettes daily and marijuana once weekly for the past 30 years. He did not drink alcohol or use illicit drugs. He worked as a manual laborer and driver. He had not traveled outside of New England. He was single and had had multiple female sexual contacts but had always used barrier protection; the young grandchild of his current sexual partner had recently had a self-limited febrile illness with a diffuse maculopapular, erythematous rash.
On examination, the patient appeared fatigued. The temperature was 37.1[degrees]C, the heart rate 89 beats per minute, the blood pressure 132/57 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. The weight was 79 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 28.1. He had mild periorbital edema and mild exfoliative scale on the temple and forehead. A blanching, maculopapular rash was present on the trunk. On the arms, legs, and dorsal feet, there were thin, faintly violaceous plaques with mild exfoliative scale. Small flaccid bullae, including some that were hemorrhagic, were noted on several fingers and the palms, and a few had ruptured (Figure 1). He did not have a rash on mucosal surfaces or nail changes. There were mildly tender, mobile lymph nodes in the bilateral cervical, submandibular, axillary, and inguinal distributions, including a 1-cm axillary node and a 2-cm inguinal node. There was mild abdominal tenderness in the upper quadrants, with hepatosplenomegaly. The stool was guaiac-negative. The remainder of the examination was normal.	
Figure 1 
Blood levels of thyrotropin, creatine kinase, troponin T, amylase, lipase, and vitamin D were normal, as were the serum osmolality, basophil count, prothrombin time, and activated partial-thromboplastin time. Other laboratory test results are shown in Table 1.
The patient was admitted to the general medicine unit. Two sets of blood cultures were obtained. Examination of a peripheral-blood smear revealed atypical-appearing mononuclear cells.
Dr. Shaunagh McDermott: On the second hospital day, CT of the chest, abdomen, and pelvis was performed after the intravenous administration of contrast material. There were areas of centrilobular emphysema and bronchial-wall thickening, scattered pulmonary nodules (2 to 3 mm in diameter) in the upper lobes, and multiple enlarged lymph nodes (Figure 2A and 2B). There was also splenomegaly (spleen length, 15.2 cm; normal length, <=12.0 cm), with a splenic cyst (Figure 2B).	
Figure 2 
Dr. Tsiaras: On the third hospital day, the temperature rose to 38.4[degrees]C and the heart rate was 110 beats per minute. Laboratory test results are shown in Table 1. Cultures of the urine and blood were obtained. Serum protein electrophoresis revealed mild, diffuse hypergammaglobulinemia, with a level of IgG lambda M component in the gamma region of 0.07 g per deciliter. Levels of serum free kappa and lambda light chains were normal. Additional imaging studies were obtained.
Dr. McDermott: Ultrasonography of the legs and arms was negative for venous thrombosis; however, enlarged lymph nodes were noted incidentally (Figure 2C). CT with positron-emission tomography (PET) was performed on the sixth hospital day. There were multiple lymph nodes with 18F-fluorodeoxyglucose (FDG) avidity in the axillary, cervical, supraclavicular, paratracheal, hilar, subcarinal, portal, iliac, and inguinal distributions, and there was diffuse increase in FDG uptake in the spleen (Figure 2D).
Dr. George Eng: Flow cytometry of a peripheral-blood specimen was negative for a monotypic B-cell population and for T cells with immunophenotypic abnormalities. Biopsy of an enlarged right inguinal lymph node was performed on the seventh hospital day; histopathological examination of the biopsy specimen revealed florid paracortical hyperplasia, without evidence of cancer (Figure 3). Flow cytometry of the biopsy specimen was negative for cancer.	
Figure 3 
Dr. Tsiaras: Diagnostic test results were received
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. The patient's symptoms of fever, rash, and organ involvement (hepatitis and lymphadenopathy), along with eosinophilia and a history of new medication initiation, are consistent with DRESS syndrome. This condition is a severe drug reaction that typically occurs two to six weeks after the initiation of a medication. The patient's symptoms began approximately five weeks after he started taking a new over-the-counter medication for pain, which he stopped taking at the onset of his symptoms. The negative results from extensive infectious, rheumatologic, and oncologic workups also support the diagnosis of a drug reaction.""
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        ""content"": ""The patient's symptoms of fever, chills, myalgias, diarrhea, and a diffuse rash, along with the presence of atypical-appearing mononuclear cells in the blood and enlarged lymph nodes, suggest a systemic illness. The negative results for infectious diseases and the absence of a monotypic B-cell population or T cells with immunophenotypic abnormalities make an infectious or lymphoproliferative disorder less likely. The patient's recent use of an unknown over-the-counter medication for pain, which he stopped taking at the onset of his symptoms, raises the possibility of a drug reaction. The presence of eosinophilia, rash, and systemic symptoms, along with the temporal association with the initiation of a new medication, suggest a diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. This syndrome is a severe, idiosyncratic reaction to a drug, characterized by a prolonged latency period, often several weeks, between drug exposure and disease onset.\n\nDiagnosis: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome.""
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        ""content"": ""The patient is a 48-year-old man presenting with fever, chills, myalgias, diarrhea, and a diffuse rash. He also has mild swelling of the face and hands, with blisters on the palms. His symptoms started about 3 weeks prior to admission and he initially thought he had influenza. His symptoms have persisted and he has been treated with an unknown antibiotic and prednisone. His medical history includes hyperlipidemia, depression, and gastroesophageal reflux disease. He has a history of smoking and marijuana use. He has not traveled outside of New England and has no known exposures to animals or insects. He has had multiple female sexual contacts but has always used barrier protection. His family history is notable for lung cancer in his mother and diabetes and coronary artery disease in his father; there is no history of autoimmune or dermatologic disorders. \n\nThe differential diagnosis for this patient includes an infectious process, an autoimmune process, or a drug reaction. Given the patient's history of smoking and marijuana use, a lung infection could be possible. However, his CT scan of the chest only revealed areas of centrilobular emphysema and bronchial-wall thickening, scattered pulmonary nodules in the upper lobes, and multiple enlarged lymph nodes. There was no evidence of pneumonia or other lung infection. His blood cultures were also negative, making a systemic bacterial infection less likely. \n\nAn autoimmune process could also be possible given his symptoms of fever, rash, and myalgias. However, his flow cytometry was negative for a monotypic B-cell population and for T cells with immunophenotypic abnormalities. This makes an autoimmune process less likely. \n\nThe patient also reported starting a new over-the-counter medication for pain approximately 5 weeks before admission. He stopped taking it at the onset of his presenting symptoms. This timeline fits with a possible drug reaction. His symptoms of fever, rash, and myalgias could be consistent with a drug reaction. His lab results also showed an elevated eosinophil count, which can be seen in drug reactions. \n\nGiven the patient's history and lab results, a drug reaction seems to be the most likely diagnosis. \n\nDiagnosis: Drug reaction.""
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10.1056/NEJMcpc1800340,Case 25-2018: A 63-Year-Old Man with Syncope,"Hemoglobin (g/dl)   13.4
Hematocrit (%)   36.7
White-cell count (per mm3)   6200
Platelet count (per mm3)   222,000
Sodium (mmol/liter)   129
Potassium (mmol/liter)   3.1
Chloride (mmol/liter)   92
Carbon dioxide (mmol/liter) 23. 1.9 22.4
Urea nitrogen (mg/dl)   10
Creatinine (mg/dl)   1.17
Glucose (mg/dl)   93
Magnesium (mg/dl)   1.5
Calcium (mg/dl)   8.4
Alanine aminotransferase (U/liter)   38
Aspartate aminotransferase (U/liter)   60
Lipase (U/liter) 13–60 128
Ethanol (mg/liter) Not defined; toxic, >1000 2347
Troponin (ng/ml) <0.03 0.04 0.03
Creatine kinase (U/liter)   887
Creatine kinase isoenzymes (ng/ml) 0.  7.8",Aortocoronary saphenous-vein‚Äö√Ñ√¨graft aneurysm.,Aortocoronary saphenous-vein–graft aneurysm.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 63-year-old man was evaluated at this hospital because of syncope.
Approximately 13 years before admission, the patient had an out-of-hospital cardiac arrest and was found to have multivessel coronary artery disease. He underwent coronary-artery bypass grafting (CABG) at another hospital, with grafting of the left internal mammary artery to the left anterior descending coronary artery, grafting of a segment of a radial artery to an obtuse marginal branch of the left circumflex coronary artery, and grafting of a saphenous vein to the posterior descending artery. Thereafter, he was followed by a local cardiologist, and he remained active and worked full-time, without cardiac symptoms or limitations.
The night before admission, the patient drank 12 beers. Later that night, after he stood up to walk to the bathroom, his wife heard a thud and found him on the floor of the bedroom. He had sustained facial trauma. She noted that he looked gray, and she started to administer chest compressions. She did not check his pulse or observe jerking movements or tongue laceration, but she noted that he may have had some urinary incontinence. The patient regained consciousness after chest compressions had been administered for a few seconds.
On evaluation by emergency medical services personnel, the patient was awake and alert. He did not recall having any prodromal symptoms, although he could not remember anything that had happened before emergency personnel had arrived. The initial heart rate was 50 beats per minute, the blood pressure 65/40 mm Hg, and the blood glucose level 98 mg per deciliter (5.4 mmol per liter) on fingerstick testing. An electrocardiogram reportedly showed horizontal ST-segment depressions of 1 mm in the inferior leads. The patient initially refused medical care, but he stumbled when he stood up, so he was brought to the emergency department of this hospital.
A review of systems was negative for chest pain, dyspnea, palpitations, light-headedness, dizziness, edema, and constitutional symptoms. The patient reported mild, progressive bilateral hearing loss and intermittent numbness of the lower legs. He had a history of hypertension, dyslipidemia, gout, varicose veins, and venous insufficiency, and he had undergone a knee replacement 9 months previously for the treatment of osteoarthritis. Medications included clopidogrel, metoprolol succinate, furosemide, ezetimibe, and allopurinol. Statin therapy had been stopped 3 months previously owing to persistent elevations in the creatine kinase level; in addition, sulfa drugs had caused a rash and aspirin use may have been associated with dyspepsia. The patient had a long-term history of alcohol consumption, typically 8 to 12 beers daily, and withdrawal symptoms had occurred in the hospital after his knee replacement. He smoked currently and had smoked up to 1 pack of cigarettes daily for 35 years. There was no history of illicit-drug use. The patient lived with his wife, had two grown children, and was employed as a mechanic. His father had died from a myocardial infarction at 56 years of age, and his mother had died from colon cancer at 76 years of age.
On examination, the temperature was 36.2[degrees]C, the heart rate 68 beats per minute, the blood pressure 100/60 mm Hg and symmetric in both arms, and the oxygen saturation 99% while the patient was breathing ambient air. He appeared to be comfortable. He had flushed skin and superficial abrasions on the left side of the forehead. The jugular venous pressure was 5 cm of water, and the carotid pulses were 2+ without bruits. A sternotomy incision was well approximated. Cardiac examination revealed a normal apical impulse and a normal rhythm, without murmur or rub. Auscultation of the lung revealed a prolonged expiratory phase, without wheezes or rales. Mild varicosities were present in the lower legs, without edema. Scars from the venectomy, knee replacement, and harvest of the left radial artery were all well healed. The stool was guaiac-negative. The remainder of the examination, including a comprehensive neurologic evaluation, was normal.
Blood levels of thyrotropin, glycated hemoglobin, phosphorus, total protein, albumin, globulin, bilirubin, and alkaline phosphatase were normal, as were the white-cell differential count, prothrombin time, and partial-thromboplastin time. Other laboratory test results are shown in Table 1. An electrocardiogram showed sinus rhythm, borderline first-degree atrioventricular block, left atrial abnormality, and anterolateral J-point elevation but no ST-segment changes (Figure 1A). Aspirin and intravenous heparin were administered, and the patient was admitted to the cardiology service. Imaging studies were obtained.	
Table 1 
Dr. Nandini M. Meyersohn: A portable chest radiograph showed clear lungs. There was borderline enlargement of the cardiomediastinal silhouette and atherosclerotic calcification of the aortic arch. The presence of mediastinal clips and sternotomy wires was consistent with the history of CABG.
Computed tomography (CT) of the head, performed without the administration of contrast material, revealed mild, diffuse cerebral parenchymal volume loss. There was prominence of the cerebrospinal fluid spaces, including the ventricles, sulci, and cisterns. There was no evidence of acute intracranial hemorrhage, territorial infarction, or intracranial mass lesion.
Dr. David M. Dudzinski: A transthoracic echocardiogram (TTE) was notable for normal left ventricular ejection fraction and cavity size, with subtle hypokinesis of the inferior wall and mild hypertrophy in the left ventricle. There was no evidence of pericardial effusion, obstruction of the left ventricular outflow tract, obvious aortic dissection, pulmonary embolism, or right ventricular dysfunction. There was sclerosis of the noncoronary leaflet of the aortic valve and the posterior mitral annulus but no evidence of clinically significant valvular disease. There appeared to be two masses with heterogeneous echotexture, measuring up to 3.8 cm in diameter, each with an echo-bright (bright white) circumference. The masses were located at the right atrioventricular groove and were compressing the tricuspid annulus at the juncture of the right atrium and the right ventricle, resulting in turbulent transtricuspid flow on color Doppler imaging (Figure 1B through 1F; and Videos 1, 2, and 3, available with the full text of this article at
NEJM.org
).
Additional diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 63-year-old man was evaluated at this hospital because of syncope.
Approximately 13 years before admission, the patient had an out-of-hospital cardiac arrest and was found to have multivessel coronary artery disease. He underwent coronary-artery bypass grafting (CABG) at another hospital, with grafting of the left internal mammary artery to the left anterior descending coronary artery, grafting of a segment of a radial artery to an obtuse marginal branch of the left circumflex coronary artery, and grafting of a saphenous vein to the posterior descending artery. Thereafter, he was followed by a local cardiologist, and he remained active and worked full-time, without cardiac symptoms or limitations.
The night before admission, the patient drank 12 beers. Later that night, after he stood up to walk to the bathroom, his wife heard a thud and found him on the floor of the bedroom. He had sustained facial trauma. She noted that he looked gray, and she started to administer chest compressions. She did not check his pulse or observe jerking movements or tongue laceration, but she noted that he may have had some urinary incontinence. The patient regained consciousness after chest compressions had been administered for a few seconds.
On evaluation by emergency medical services personnel, the patient was awake and alert. He did not recall having any prodromal symptoms, although he could not remember anything that had happened before emergency personnel had arrived. The initial heart rate was 50 beats per minute, the blood pressure 65/40 mm Hg, and the blood glucose level 98 mg per deciliter (5.4 mmol per liter) on fingerstick testing. An electrocardiogram reportedly showed horizontal ST-segment depressions of 1 mm in the inferior leads. The patient initially refused medical care, but he stumbled when he stood up, so he was brought to the emergency department of this hospital.
A review of systems was negative for chest pain, dyspnea, palpitations, light-headedness, dizziness, edema, and constitutional symptoms. The patient reported mild, progressive bilateral hearing loss and intermittent numbness of the lower legs. He had a history of hypertension, dyslipidemia, gout, varicose veins, and venous insufficiency, and he had undergone a knee replacement 9 months previously for the treatment of osteoarthritis. Medications included clopidogrel, metoprolol succinate, furosemide, ezetimibe, and allopurinol. Statin therapy had been stopped 3 months previously owing to persistent elevations in the creatine kinase level; in addition, sulfa drugs had caused a rash and aspirin use may have been associated with dyspepsia. The patient had a long-term history of alcohol consumption, typically 8 to 12 beers daily, and withdrawal symptoms had occurred in the hospital after his knee replacement. He smoked currently and had smoked up to 1 pack of cigarettes daily for 35 years. There was no history of illicit-drug use. The patient lived with his wife, had two grown children, and was employed as a mechanic. His father had died from a myocardial infarction at 56 years of age, and his mother had died from colon cancer at 76 years of age.
On examination, the temperature was 36.2[degrees]C, the heart rate 68 beats per minute, the blood pressure 100/60 mm Hg and symmetric in both arms, and the oxygen saturation 99% while the patient was breathing ambient air. He appeared to be comfortable. He had flushed skin and superficial abrasions on the left side of the forehead. The jugular venous pressure was 5 cm of water, and the carotid pulses were 2+ without bruits. A sternotomy incision was well approximated. Cardiac examination revealed a normal apical impulse and a normal rhythm, without murmur or rub. Auscultation of the lung revealed a prolonged expiratory phase, without wheezes or rales. Mild varicosities were present in the lower legs, without edema. Scars from the venectomy, knee replacement, and harvest of the left radial artery were all well healed. The stool was guaiac-negative. The remainder of the examination, including a comprehensive neurologic evaluation, was normal.
Blood levels of thyrotropin, glycated hemoglobin, phosphorus, total protein, albumin, globulin, bilirubin, and alkaline phosphatase were normal, as were the white-cell differential count, prothrombin time, and partial-thromboplastin time. Other laboratory test results are shown in Table 1. An electrocardiogram showed sinus rhythm, borderline first-degree atrioventricular block, left atrial abnormality, and anterolateral J-point elevation but no ST-segment changes (Figure 1A). Aspirin and intravenous heparin were administered, and the patient was admitted to the cardiology service. Imaging studies were obtained.	
Table 1 
Dr. Nandini M. Meyersohn: A portable chest radiograph showed clear lungs. There was borderline enlargement of the cardiomediastinal silhouette and atherosclerotic calcification of the aortic arch. The presence of mediastinal clips and sternotomy wires was consistent with the history of CABG.
Computed tomography (CT) of the head, performed without the administration of contrast material, revealed mild, diffuse cerebral parenchymal volume loss. There was prominence of the cerebrospinal fluid spaces, including the ventricles, sulci, and cisterns. There was no evidence of acute intracranial hemorrhage, territorial infarction, or intracranial mass lesion.
Dr. David M. Dudzinski: A transthoracic echocardiogram (TTE) was notable for normal left ventricular ejection fraction and cavity size, with subtle hypokinesis of the inferior wall and mild hypertrophy in the left ventricle. There was no evidence of pericardial effusion, obstruction of the left ventricular outflow tract, obvious aortic dissection, pulmonary embolism, or right ventricular dysfunction. There was sclerosis of the noncoronary leaflet of the aortic valve and the posterior mitral annulus but no evidence of clinically significant valvular disease. There appeared to be two masses with heterogeneous echotexture, measuring up to 3.8 cm in diameter, each with an echo-bright (bright white) circumference. The masses were located at the right atrioventricular groove and were compressing the tricuspid annulus at the juncture of the right atrium and the right ventricle, resulting in turbulent transtricuspid flow on color Doppler imaging (Figure 1B through 1F; and Videos 1, 2, and 3, available with the full text of this article at
NEJM.org
).
Additional diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 63-year-old man with a history of multivessel coronary artery disease and coronary-artery bypass grafting (CABG) who presented with syncope. He has a history of hypertension, dyslipidemia, gout, varicose veins, and venous insufficiency. He also has a long-term history of alcohol consumption and smoking. The differential diagnosis for this patient includes cardiac arrhythmia, myocardial infarction, transient ischemic attack (TIA), stroke, and alcohol withdrawal. The patient's EKG showed sinus rhythm, borderline first-degree atrioventricular block, left atrial abnormality, and anterolateral J-point elevation but no ST-segment changes, which makes myocardial infarction less likely. The CT of the head did not show any evidence of acute intracranial hemorrhage, territorial infarction, or intracranial mass lesion, which makes TIA or stroke less likely. The patient did not show any signs of alcohol withdrawal. The transthoracic echocardiogram (TTE) showed two masses with heterogeneous echotexture, measuring up to 3.8 cm in diameter, each with an echo-bright (bright white) circumference. The masses were located at the right atrioventricular groove and were compressing the tricuspid annulus at the juncture of the right atrium and the right ventricle, resulting in turbulent transtricuspid flow on color Doppler imaging. This finding is most consistent with cardiac tumors, which could have caused the patient's syncope by obstructing blood flow.\n\nDiagnosis: Cardiac tumors.""
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10.1056/NEJMcpc1802829,Case 24-2018: A 71-Year-Old Man with Acute Renal Failure and Hematuria,"Hemoglobin (g/dl)  13.5 11.0   10.8
Hematocrit (%)  39.8 33.6   32.1
White-cell count (per mm3)   16,500 11,600   16,580
Differential count (%)
Neutrophils 76.1 71.5  
Lymphocytes 12.6 14.5  
Monocytes 9.2 10.2  
Eosinophils 0.6 0.7  
Basophils 0.3 0.3  
Immature granulocytes 1.2 2.8 
Platelet count (per mm3
)   388,000 461,000   300,000
Sodium (mmol/liter)  140 144   143
Potassium (mmol/liter)  4.1 4.0   3.5
Chloride (mmol/liter)  100 109   107
Carbon dioxide (mmol/liter)   26 23   23
Urea nitrogen (mg/dl)  72 58   50
Creatinine (mg/dl)  4.6 3.9   2.78
Glucose (mg/dl) 70–100 101 93   99
Calcium (mg/dl) 8.6–10.3 8.8   7.9
Total protein (g/dl) 6.4–8.3 6.6 6. .3 5.1
Albumin (g/dl) 4.  3.0   2.4
Glycated hemoglobin (%) 4.3–5.9 5.9
Erythrocyte sedimentation rate (mm/hr)  0 82
Antinuclear antibody Negative Negative Negative at 1:40 
and 1:160
Positive at 1:40; 
negative at 1:80 
and 1:160
Antiproteinase 3 antineutrophil cytoplasmic 
antibody
<0.2 U <0.2 U Negative Negative
Antimyeloperoxidase antineutrophil cytoplasmic 
antibody
<0.4 U <0.2 U Negative Negative
C3 (mg/dl) 75–175 153 81–157 114
C4 (mg/dl) 14–40 30 12–39 21
Anti–double-stranded DNA Negative at 1:10 Negative at 1:10
Rheumatoid factor (U/ml)  0 31
Hepatitis B surface antigen Negative Negative
Hepatitis B surface antibody Negative Negative
Hepatitis B core antibody Negative Negative
Hepatitis C antibody Negative Negative
Antitreponemal antibody Negative Negative
Prostate-specific antigen (ng/dl) 0–4.0 <0.10
Kappa light chain (mg/liter)   32.4
Lambda light chain (mg/liter)   30.9                                                          Iron (μg/dl) 45–160 25
Iron-binding capacity (μg/dl) 23 4 146
Ferritin (μg/liter) 2 00 603
Transferrin (mg/dl) 20 60 121
Urine
Color Yellow Yellow Yellow Yellow Rose
Clarity Clear Clear Clear Clear Slightly cloudy
pH 5. .0 5.0 5.0   6.0
Specific gravity 1.003–1.030 1.010 1.009   1.008
Protein Negative 100 mg/dl 100 mg/dl Negative 2+
Glucose Negative Negative Negative Negative Negative
Ketones Negative Negative Negative Negative Negative
Blood Negative Large Negative Negative 3+
Bilirubin Negative Negative Negative Negative Negative
Nitrite Negative Negative Negative Negative Negative
Leukocyte esterase Negative Negative Negative Negative Negative
Red cells (per high-power field)   111 35   >100
Leukocytes (per high-power field) 0–5 15 11   1 0
Eosinophils (%) 0 2
Bacteria Negative Few Negative 1+
Sodium (mmol/liter) <20 43
Creatinine (mg/dl) 39. 59.0 101.0 85.0 57
Total protein (mg/dl) 198.3  .5 325.3
Microalbumin (mg/dl)  .0 194.5
Ratio of total protein (in mg) to creatinine (in mg)  2.3  5.71
Ratio of microalbumin (in mg) to creatinine (in g) 3412.3",Anti‚Äö√Ñ√¨glomerular basement membrane disease.,"Anti–glomerular basement membrane disease causing a crescentic glomerulonephritis.

Diverticulitis due to Bacteroides fragilis and other gram-negative anaerobic bacteria.

Podocytopathy, possibly due to mild diabetic nephropathy.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 71-year-old man was transferred to this hospital because of worsening renal function and hematuria.
Three weeks before this admission, the patient's wife became ill with chills, fatigue, and myalgias, and she thought she had influenza. A few days later, the patient reportedly had a subjective fever, with intermittent shaking chills, fatigue, malaise, anorexia, and mild diffuse myalgias. He noted that he had reduced his fluid intake and that his urine had become darker. His symptoms were temporarily relieved with the administration of acetaminophen.
Approximately 10 days before this admission, the patient was evaluated by his primary care physician, who thought the patient was dehydrated. Laboratory tests were performed, and the results came back later that day, revealing a serum creatinine level of 4.9 mg per deciliter (433 [mu]mol per liter; reference range, 0.6 to 1.4 mg per deciliter [53 to 124 [mu]mol per liter]); the creatinine level had been 0.8 mg per deciliter (71 [mu]mol per liter) 2 months earlier. He was referred to the emergency department of another hospital.
On evaluation at the other hospital, the patient reported persistent constitutional symptoms, intermittent lower abdominal cramping, and increased darkening of the urine, which had become the color of cola. The temperature was 36.9[degrees]C, the heart rate 87 beats per minute, the blood pressure 153/82 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. The weight was 103.2 kg, and the mucous membranes were moist. The remainder of the examination was normal. Testing of a nasopharyngeal swab for influenza A and B viruses was negative, and a urine culture was obtained; other laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
A chest radiograph was reportedly normal. Computed tomography (CT) of the abdomen and pelvis, performed without the intravenous administration of contrast material, reportedly revealed bilateral renal cysts without evidence of hydronephrosis, diverticulosis without evidence of diverticulitis, cholelithiasis without evidence of cholecystitis, and vascular calcifications of the abdominal aorta, with an abdominal aortic aneurysm (3.9 cm in diameter).
Intravenous normal saline was administered, and the patient was admitted to the other hospital. His outpatient medications were aspirin, atorvastatin, amlodipine with benazepril, metformin, cholecalciferol, and n-3 fatty acids, as well as ibuprofen every other day for knee pain. Ibuprofen, aspirin, benazepril, and metformin were discontinued on admission.
Renal ultrasonography revealed normal-sized kidneys (13.3 cm on the right and 11.8 cm on the left), with bilateral cysts (<=5.5 cm in diameter), including one with a thin septation, and no evidence of hydronephrosis. A nephrology consultation was obtained; additional test results are shown in Table 1. On hospital day 4, the creatinine level decreased to 3.2 mg per deciliter (283 [mu]mol per liter), but over the next 2 days, hematuria occurred and the creatinine level increased to 3.9 mg per deciliter (345 [mu]mol per liter). Examination of the urinary sediment revealed red cells, red-cell casts, and white-cell casts. Empirical treatment with intravenous methylprednisolone was started, and a plan was made for kidney biopsy.
Because the patient had temperatures of up to 37.7[degrees]C and persistent leukocytosis, two sets of blood cultures were obtained. Two days later, gram-negative rods grew in the two anaerobic bottles. Treatment with intravenous ceftriaxone was started, and methylprednisolone was discontinued. Repeat cultures of the blood and urine were obtained, ceftriaxone was discontinued, and treatment with cefepime and aztreonam was started.
Repeat CT of the abdomen and pelvis, performed without the intravenous administration of contrast material, revealed an increased amount of perinephric fluid without evidence of a discrete abscess. It also revealed a hyperintense renal cyst (0.9 cm in diameter) in the right upper pole, new evidence of presacral fat stranding, and trace bilateral pleural effusions. An echocardiogram showed normal ventricular function and no valvular calcifications. On hospital day 11, the creatinine level was 3.0 mg per deciliter (265 [mu]mol per liter), and the patient requested transfer to this hospital.
On evaluation at this hospital, a review of systems was notable for gross hematuria with brown urine, fatigue, low-grade fevers, anorexia, and intermittent cough. The patient reported diffuse crampy abdominal pain that he rated at 3 on a scale ranging from 0 (no pain) to 10 (the most severe pain). He reported that he had no dysuria, increase in urinary frequency, flank pain, nausea, vomiting, pharyngitis, dyspnea, rash, headache, or neurologic symptoms.
The patient had a history of impaired glucose tolerance, hypertension, hyperlipidemia, abdominal aortic aneurysm, eczema, benign colonic polyps, diverticulosis, and osteoarthritis of the knees, shoulders, and lumbar spine. He had undergone right inguinal hernia repair, as well as radical prostatectomy for the treatment of prostate cancer 16 years previously. He had had no adverse reactions to medications. Several of his five young grandchildren had been ill during the month before this admission. He had retired 1 year earlier from a job in sales, which had involved travel to Europe and most recently to Mexico. He had drunk 3 or 4 beers daily since he had retired. He had smoked a half pack of cigarettes daily for 50 years but had most recently smoked a few cigarettes per day. His father had had lung cancer and his mother had had diabetes, but there was no family history of autoimmune or renal disease.
On physical examination, the temperature was 37.4[degrees]C, the heart rate 84 beats per minute, the blood pressure 159/90 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. The weight was 103.6 kg, the height 175 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 33.8. The patient appeared comfortable. Dentition was poor, but there were no oropharyngeal lesions. Auscultation of the chest revealed an early-peaking systolic murmur (grade 2/6) at the left base and bibasilar crackles. The abdomen was soft, nontender, and nondistended, and there was no tenderness at the costovertebral angle. A left inguinal hernia was present. There were no septic lesions on the nails and no rashes. Voided urine was rose-colored, without clots. The rest of the examination was normal.
Cultures of the urine and blood were obtained. Blood levels of magnesium, phosphorus, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin were normal. Other laboratory test results are shown in Table 1. Examination of the urinary sediment revealed nondysmorphic red cells that were ""too numerous to count,"" a few granular casts, and no cellular casts. Results of serum protein electrophoresis were normal, and a urine test for Bence Jones protein was negative.
Dr. Jad S. Husseini: CT of the abdomen and pelvis was performed without the intravenous administration of contrast material (Figure 1). There was mild bilateral perinephric stranding with no hydronephrosis. The kidneys contained multiple, bilateral simple renal cortical cysts. There was colonic diverticulosis, predominantly involving the sigmoid colon, with fat stranding and multiple prominent lymph nodes in the sigmoid mesentery. These findings were compatible with acute sigmoid diverticulitis. The peritoneum contained a trace amount of free fluid and no free air. There were vascular calcifications involving the abdominal aorta and its major branches, with an infrarenal abdominal aortic aneurysm (3.9 cm in diameter). The lung bases were clear. There were trace bilateral pleural effusions.	
Figure 1 
Dr. Drago: Intravenous ceftazidime and metronidazole were administered. On hospital day 2, crampy abdominal and suprapubic pain occurred and the urine appeared darker red. Diagnostic tests were performed
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 71-year-old man was transferred to this hospital because of worsening renal function and hematuria.
Three weeks before this admission, the patient's wife became ill with chills, fatigue, and myalgias, and she thought she had influenza. A few days later, the patient reportedly had a subjective fever, with intermittent shaking chills, fatigue, malaise, anorexia, and mild diffuse myalgias. He noted that he had reduced his fluid intake and that his urine had become darker. His symptoms were temporarily relieved with the administration of acetaminophen.
Approximately 10 days before this admission, the patient was evaluated by his primary care physician, who thought the patient was dehydrated. Laboratory tests were performed, and the results came back later that day, revealing a serum creatinine level of 4.9 mg per deciliter (433 [mu]mol per liter; reference range, 0.6 to 1.4 mg per deciliter [53 to 124 [mu]mol per liter]); the creatinine level had been 0.8 mg per deciliter (71 [mu]mol per liter) 2 months earlier. He was referred to the emergency department of another hospital.
On evaluation at the other hospital, the patient reported persistent constitutional symptoms, intermittent lower abdominal cramping, and increased darkening of the urine, which had become the color of cola. The temperature was 36.9[degrees]C, the heart rate 87 beats per minute, the blood pressure 153/82 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. The weight was 103.2 kg, and the mucous membranes were moist. The remainder of the examination was normal. Testing of a nasopharyngeal swab for influenza A and B viruses was negative, and a urine culture was obtained; other laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
A chest radiograph was reportedly normal. Computed tomography (CT) of the abdomen and pelvis, performed without the intravenous administration of contrast material, reportedly revealed bilateral renal cysts without evidence of hydronephrosis, diverticulosis without evidence of diverticulitis, cholelithiasis without evidence of cholecystitis, and vascular calcifications of the abdominal aorta, with an abdominal aortic aneurysm (3.9 cm in diameter).
Intravenous normal saline was administered, and the patient was admitted to the other hospital. His outpatient medications were aspirin, atorvastatin, amlodipine with benazepril, metformin, cholecalciferol, and n-3 fatty acids, as well as ibuprofen every other day for knee pain. Ibuprofen, aspirin, benazepril, and metformin were discontinued on admission.
Renal ultrasonography revealed normal-sized kidneys (13.3 cm on the right and 11.8 cm on the left), with bilateral cysts (<=5.5 cm in diameter), including one with a thin septation, and no evidence of hydronephrosis. A nephrology consultation was obtained; additional test results are shown in Table 1. On hospital day 4, the creatinine level decreased to 3.2 mg per deciliter (283 [mu]mol per liter), but over the next 2 days, hematuria occurred and the creatinine level increased to 3.9 mg per deciliter (345 [mu]mol per liter). Examination of the urinary sediment revealed red cells, red-cell casts, and white-cell casts. Empirical treatment with intravenous methylprednisolone was started, and a plan was made for kidney biopsy.
Because the patient had temperatures of up to 37.7[degrees]C and persistent leukocytosis, two sets of blood cultures were obtained. Two days later, gram-negative rods grew in the two anaerobic bottles. Treatment with intravenous ceftriaxone was started, and methylprednisolone was discontinued. Repeat cultures of the blood and urine were obtained, ceftriaxone was discontinued, and treatment with cefepime and aztreonam was started.
Repeat CT of the abdomen and pelvis, performed without the intravenous administration of contrast material, revealed an increased amount of perinephric fluid without evidence of a discrete abscess. It also revealed a hyperintense renal cyst (0.9 cm in diameter) in the right upper pole, new evidence of presacral fat stranding, and trace bilateral pleural effusions. An echocardiogram showed normal ventricular function and no valvular calcifications. On hospital day 11, the creatinine level was 3.0 mg per deciliter (265 [mu]mol per liter), and the patient requested transfer to this hospital.
On evaluation at this hospital, a review of systems was notable for gross hematuria with brown urine, fatigue, low-grade fevers, anorexia, and intermittent cough. The patient reported diffuse crampy abdominal pain that he rated at 3 on a scale ranging from 0 (no pain) to 10 (the most severe pain). He reported that he had no dysuria, increase in urinary frequency, flank pain, nausea, vomiting, pharyngitis, dyspnea, rash, headache, or neurologic symptoms.
The patient had a history of impaired glucose tolerance, hypertension, hyperlipidemia, abdominal aortic aneurysm, eczema, benign colonic polyps, diverticulosis, and osteoarthritis of the knees, shoulders, and lumbar spine. He had undergone right inguinal hernia repair, as well as radical prostatectomy for the treatment of prostate cancer 16 years previously. He had had no adverse reactions to medications. Several of his five young grandchildren had been ill during the month before this admission. He had retired 1 year earlier from a job in sales, which had involved travel to Europe and most recently to Mexico. He had drunk 3 or 4 beers daily since he had retired. He had smoked a half pack of cigarettes daily for 50 years but had most recently smoked a few cigarettes per day. His father had had lung cancer and his mother had had diabetes, but there was no family history of autoimmune or renal disease.
On physical examination, the temperature was 37.4[degrees]C, the heart rate 84 beats per minute, the blood pressure 159/90 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. The weight was 103.6 kg, the height 175 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 33.8. The patient appeared comfortable. Dentition was poor, but there were no oropharyngeal lesions. Auscultation of the chest revealed an early-peaking systolic murmur (grade 2/6) at the left base and bibasilar crackles. The abdomen was soft, nontender, and nondistended, and there was no tenderness at the costovertebral angle. A left inguinal hernia was present. There were no septic lesions on the nails and no rashes. Voided urine was rose-colored, without clots. The rest of the examination was normal.
Cultures of the urine and blood were obtained. Blood levels of magnesium, phosphorus, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin were normal. Other laboratory test results are shown in Table 1. Examination of the urinary sediment revealed nondysmorphic red cells that were ""too numerous to count,"" a few granular casts, and no cellular casts. Results of serum protein electrophoresis were normal, and a urine test for Bence Jones protein was negative.
Dr. Jad S. Husseini: CT of the abdomen and pelvis was performed without the intravenous administration of contrast material (Figure 1). There was mild bilateral perinephric stranding with no hydronephrosis. The kidneys contained multiple, bilateral simple renal cortical cysts. There was colonic diverticulosis, predominantly involving the sigmoid colon, with fat stranding and multiple prominent lymph nodes in the sigmoid mesentery. These findings were compatible with acute sigmoid diverticulitis. The peritoneum contained a trace amount of free fluid and no free air. There were vascular calcifications involving the abdominal aorta and its major branches, with an infrarenal abdominal aortic aneurysm (3.9 cm in diameter). The lung bases were clear. There were trace bilateral pleural effusions.	
Figure 1 
Dr. Drago: Intravenous ceftazidime and metronidazole were administered. On hospital day 2, crampy abdominal and suprapubic pain occurred and the urine appeared darker red. Diagnostic tests were performed
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fever, fatigue, myalgias, and dark urine, along with the laboratory findings of elevated creatinine levels and hematuria, suggest a renal disorder. The presence of red cells, red-cell casts, and white-cell casts in the urinary sediment further supports a glomerular disease. The patient's recent history of a possible influenza-like illness raises the possibility of a post-infectious glomerulonephritis. However, the patient's age and the presence of gram-negative rods in blood cultures suggest an infectious process, possibly endocarditis, which can also cause glomerulonephritis. The absence of valvular vegetations on echocardiogram makes endocarditis less likely. The patient's recent travel to Mexico and daily beer consumption raise the possibility of an infection with leptospirosis, which can cause a similar clinical picture. The patient's exposure to young grandchildren who had been ill could suggest an infection with adenovirus, which can also cause glomerulonephritis. However, the presence of gram-negative rods in blood cultures and the patient's response to antibiotic therapy suggest a bacterial infection as the most likely cause of the patient's symptoms.\n\nDiagnosis: Bacterial endocarditis-induced glomerulonephritis.""
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        ""content"": ""The patient's symptoms of fever, fatigue, malaise, anorexia, myalgias, and dark urine, along with the laboratory findings of elevated creatinine levels and hematuria, suggest a kidney-related issue. The presence of red cells, red-cell casts, and white-cell casts in the urinary sediment further supports this. The patient's history of hypertension, hyperlipidemia, abdominal aortic aneurysm, and prostate cancer, along with his smoking and alcohol habits, put him at risk for kidney disease. The patient's symptoms did not improve with hydration, suggesting that the kidney issue is not simply due to dehydration. The presence of gram-negative rods in the blood cultures suggests a bacterial infection, which could have spread to the kidneys, causing an infection there. The CT scan revealed bilateral renal cysts, which could be the source of the infection. The patient's symptoms and lab findings did not improve with antibiotic treatment, suggesting that the kidney issue is not solely due to a bacterial infection. The patient's history of prostate cancer raises the possibility of cancer spreading to the kidneys, but this is less likely given the lack of other symptoms of cancer, such as weight loss. The patient's symptoms and lab findings are most consistent with glomerulonephritis, an inflammation of the glomeruli in the kidneys. This can be caused by a variety of conditions, including infections, autoimmune diseases, and certain medications. The patient's history of prostate cancer and use of certain medications, such as ibuprofen and aspirin, could have contributed to the development of glomerulonephritis.\n\nDiagnosis: Glomerulonephritis.""
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        ""content"": ""This is a 71-year-old man with a history of hypertension, hyperlipidemia, abdominal aortic aneurysm, eczema, benign colonic polyps, diverticulosis, and osteoarthritis who presents with worsening renal function and hematuria. His symptoms began with a subjective fever, chills, fatigue, malaise, anorexia, and myalgias, which were temporarily relieved with acetaminophen. He also reported reduced fluid intake and darkening of his urine. His creatinine level was found to be significantly elevated compared to two months prior. He was admitted to the hospital and his outpatient medications were adjusted. His creatinine level initially decreased, but then increased again and he developed hematuria. He was started on methylprednisolone and a plan was made for a kidney biopsy. However, he developed a fever and leukocytosis, and blood cultures grew gram-negative rods. He was started on antibiotics and transferred to this hospital. \n\nThe differential diagnosis for this patient includes acute interstitial nephritis, glomerulonephritis, and infection-related glomerulonephritis. Acute interstitial nephritis is often drug-induced and can present with fever, rash, and eosinophilia, but this patient's presentation is not typical and he does not have eosinophilia. Glomerulonephritis can present with hematuria and renal failure, but it is usually associated with hypertension, edema, and proteinuria, which this patient does not have. Infection-related glomerulonephritis can occur after a bacterial infection and can present with hematuria, hypertension, edema, and renal failure. This patient does have a bacterial infection and hematuria, but he does not have hypertension or edema. \n\nGiven the patient's presentation and the fact that his symptoms began after his wife had influenza-like symptoms, it is possible that he has an infection-related glomerulonephritis. His renal failure and hematuria could be due to glomerular damage caused by an immune response to the infection. The presence of gram-negative rods in his blood cultures suggests a bacterial infection, which could have triggered the immune response. \n\nDiagnosis: Infection-related glomerulonephritis.""
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10.1056/NEJMcpc1802828,Case 23-2018: A 36-Year-Old Man with Episodes of Confusion and Hypoglycemia,,"Well-differentiated pancreatic neuroendocrine tumor, grade 1",Insulinoma,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 36-year-old man was admitted to this hospital because of episodes of altered mental status.
The patient had been well until 6 years before admission, when his wife observed an episode of unusual behavior. During the episode, the patient was found wandering through his home, confused about where he was. He had nonsensical speech and nonpurposeful movements of the arms, and he described having blurry vision. The patient's wife noted that he appeared to be aware that his speech was nonsensical. The patient returned to his normal baseline mental status after 30 minutes. He was not able to recall the details of the episode and did not seek medical care.
Two years before admission, the patient began to have similar episodes one or two times per year. Four months before admission, the episodes became more frequent, occurring one or two times per month. The episodes most often occurred at night after the patient had consumed alcohol. Despite decreasing his alcohol intake from five to six beers several times per week to two to four beers several times per week, he continued to have intermittent periods of altered mental status and nonsensical speech. He attributed the episodes to stress and did not seek medical care.
One day before admission, the patient's wife noted that the patient was ""not himself"" when he became uncharacteristically upset after learning, while he and his wife were out to dinner, that one of their daughters had had nausea, vomiting, and fever at home. He again had nonsensical speech, along with nonpurposeful jerking movements of his hands. These symptoms diminished after he ate the meal. After the symptoms resolved, the patient noted that he had eaten very little during the day.
On the day of admission, the patient vomited early in the morning. Afterward, he appeared diaphoretic, was intermittently confused during the day, and had symptoms similar to those of previous episodes. In the afternoon, he had a telephone conversation with a friend during which he was speaking nonsensically, and the friend became concerned. After speaking with the patient's wife, the friend brought the patient to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported no headaches, numbness, tingling, paralysis, gait changes, weakness, or incontinence. He had no tongue biting, fevers, chills, weight loss, abdominal pain, diarrhea, dysuria, shortness of breath, or chest pain. Thirteen years before admission, he had received a diagnosis of eosinophilic esophagitis, which had been complicated by multiple episodes of food impaction that necessitated esophageal dilation. Eleven years before admission, he had undergone sternotomy and laparotomy for repair of an inferior vena cava injury after he had received an abdominal stab wound. The patient took no medications and had no known allergies. He lived with his wife and two young children and worked as a firefighter. He drank two to four beers twice weekly and had quit smoking tobacco 14 years before this presentation. He did not use illicit drugs. His two paternal uncles had alcohol-use disorder. His father had melanoma, his mother had an arteriovenous malformation involving the central nervous system, and a younger brother had lung cancer. There was no family history of heart, pancreatic, or autoimmune disease, and no one in the patient's home used insulin or other diabetes medications.
On examination, the temperature was 36.5[degrees]C, the blood pressure 135/85 mm Hg, the heart rate 103 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 69 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 22.5. Seven months before admission, the weight had been 70 kg. The patient was confused and agitated, rocking back and forth. He intermittently placed his head between the side rails of his stretcher. He was oriented to person and place and knew the name of the president but did not know the date. Attention, concentration, abstract reasoning, and memory were poor. The patient was unable to calculate the number of quarters (a coin worth 25 cents) in $2.25 but could calculate the number of quarters in $1.00. Asterixis and vertical nystagmus were present; the remainder of the neurologic and general examination was normal.
In the emergency department, the blood glucose level was 38 mg per deciliter (2.1 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). A complete blood count and levels of electrolytes, thyrotropin, and creatine kinase were normal, as were results of liver- and renal-function tests. Serum and urine toxicology screening tests were negative. The C-reactive protein level was 48 mg per liter (reference range,  .0), and the erythrocyte sedimentation rate was 38 mm per hour (reference range, 0 to 20). Ninety minutes after the initial blood glucose level was obtained, the glucose level, obtained by fingerstick testing, was 20 mg per deciliter (1.1 mmol per liter). A bolus containing a solution of 20% dextrose in water was administered intravenously. The glucose level, obtained by fingerstick testing, rose to 257 mg per deciliter (14.3 mmol per liter), and the patient was no longer confused or agitated. On a repeat neurologic examination, the mental-status examination was normal. Urinalysis performed after the administration of glucose revealed 3+ glucose and 1+ ketones and was otherwise normal. Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 36-year-old man was admitted to this hospital because of episodes of altered mental status.
The patient had been well until 6 years before admission, when his wife observed an episode of unusual behavior. During the episode, the patient was found wandering through his home, confused about where he was. He had nonsensical speech and nonpurposeful movements of the arms, and he described having blurry vision. The patient's wife noted that he appeared to be aware that his speech was nonsensical. The patient returned to his normal baseline mental status after 30 minutes. He was not able to recall the details of the episode and did not seek medical care.
Two years before admission, the patient began to have similar episodes one or two times per year. Four months before admission, the episodes became more frequent, occurring one or two times per month. The episodes most often occurred at night after the patient had consumed alcohol. Despite decreasing his alcohol intake from five to six beers several times per week to two to four beers several times per week, he continued to have intermittent periods of altered mental status and nonsensical speech. He attributed the episodes to stress and did not seek medical care.
One day before admission, the patient's wife noted that the patient was ""not himself"" when he became uncharacteristically upset after learning, while he and his wife were out to dinner, that one of their daughters had had nausea, vomiting, and fever at home. He again had nonsensical speech, along with nonpurposeful jerking movements of his hands. These symptoms diminished after he ate the meal. After the symptoms resolved, the patient noted that he had eaten very little during the day.
On the day of admission, the patient vomited early in the morning. Afterward, he appeared diaphoretic, was intermittently confused during the day, and had symptoms similar to those of previous episodes. In the afternoon, he had a telephone conversation with a friend during which he was speaking nonsensically, and the friend became concerned. After speaking with the patient's wife, the friend brought the patient to the emergency department of this hospital for evaluation.
In the emergency department, the patient reported no headaches, numbness, tingling, paralysis, gait changes, weakness, or incontinence. He had no tongue biting, fevers, chills, weight loss, abdominal pain, diarrhea, dysuria, shortness of breath, or chest pain. Thirteen years before admission, he had received a diagnosis of eosinophilic esophagitis, which had been complicated by multiple episodes of food impaction that necessitated esophageal dilation. Eleven years before admission, he had undergone sternotomy and laparotomy for repair of an inferior vena cava injury after he had received an abdominal stab wound. The patient took no medications and had no known allergies. He lived with his wife and two young children and worked as a firefighter. He drank two to four beers twice weekly and had quit smoking tobacco 14 years before this presentation. He did not use illicit drugs. His two paternal uncles had alcohol-use disorder. His father had melanoma, his mother had an arteriovenous malformation involving the central nervous system, and a younger brother had lung cancer. There was no family history of heart, pancreatic, or autoimmune disease, and no one in the patient's home used insulin or other diabetes medications.
On examination, the temperature was 36.5[degrees]C, the blood pressure 135/85 mm Hg, the heart rate 103 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 69 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 22.5. Seven months before admission, the weight had been 70 kg. The patient was confused and agitated, rocking back and forth. He intermittently placed his head between the side rails of his stretcher. He was oriented to person and place and knew the name of the president but did not know the date. Attention, concentration, abstract reasoning, and memory were poor. The patient was unable to calculate the number of quarters (a coin worth 25 cents) in $2.25 but could calculate the number of quarters in $1.00. Asterixis and vertical nystagmus were present; the remainder of the neurologic and general examination was normal.
In the emergency department, the blood glucose level was 38 mg per deciliter (2.1 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). A complete blood count and levels of electrolytes, thyrotropin, and creatine kinase were normal, as were results of liver- and renal-function tests. Serum and urine toxicology screening tests were negative. The C-reactive protein level was 48 mg per liter (reference range,  .0), and the erythrocyte sedimentation rate was 38 mm per hour (reference range, 0 to 20). Ninety minutes after the initial blood glucose level was obtained, the glucose level, obtained by fingerstick testing, was 20 mg per deciliter (1.1 mmol per liter). A bolus containing a solution of 20% dextrose in water was administered intravenously. The glucose level, obtained by fingerstick testing, rose to 257 mg per deciliter (14.3 mmol per liter), and the patient was no longer confused or agitated. On a repeat neurologic examination, the mental-status examination was normal. Urinalysis performed after the administration of glucose revealed 3+ glucose and 1+ ketones and was otherwise normal. Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Insulinoma. The patient's episodes of altered mental status, nonsensical speech, and nonpurposeful movements of the arms, which were often triggered by alcohol consumption or fasting and resolved with food intake, suggest hypoglycemia. The patient's low blood glucose level in the emergency department confirms this. The presence of glucose and ketones in the urine after administration of glucose suggests that the patient's body had been breaking down fat for energy, a process that occurs when insulin is not available to help cells take in glucose. This, along with the fact that the patient's symptoms resolved after administration of glucose, suggests that the hypoglycemia was due to an excess of insulin. The most likely cause of this is an insulinoma, a tumor of the insulin-producing cells in the pancreas.""
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        ""content"": ""The patient's episodes of altered mental status, nonsensical speech, and nonpurposeful movements of the arms, along with blurry vision, are suggestive of a neurological issue. However, the fact that these symptoms are resolved after eating, and the extremely low blood glucose levels recorded in the emergency department, suggest that these episodes are due to hypoglycemia. The patient's symptoms improve after administration of glucose, further supporting this diagnosis. The patient does not have a history of diabetes and is not on any medications, ruling out iatrogenic hypoglycemia. The presence of ketones in the urine after glucose administration suggests that the body had been breaking down fats for energy due to lack of glucose, which is consistent with insulinoma, a tumor of the pancreas that overproduces insulin leading to hypoglycemia. \n\nDiagnosis: Insulinoma.""
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        ""content"": ""The patient is a 36-year-old man presenting with episodes of altered mental status, nonsensical speech, nonpurposeful movements of the arms, and blurry vision. These episodes are often preceded by alcohol consumption and stress, and are resolved by eating. The patient also has a history of eosinophilic esophagitis. The differential diagnosis for this patient includes hypoglycemia, transient ischemic attack (TIA), epilepsy, and psychiatric disorders such as schizophrenia or bipolar disorder. The patient's symptoms do not include headaches, numbness, tingling, paralysis, gait changes, weakness, or incontinence, which makes TIA less likely. The patient's symptoms are also not consistent with the typical presentation of epilepsy, which often includes a loss of consciousness and convulsions. The patient's symptoms are also not consistent with the typical presentation of schizophrenia or bipolar disorder, which often include delusions, hallucinations, and mood swings. The patient's symptoms are most consistent with hypoglycemia, which can cause altered mental status, nonsensical speech, and blurry vision. The patient's symptoms are often preceded by alcohol consumption and stress, both of which can cause hypoglycemia. The patient's symptoms are also resolved by eating, which increases blood glucose levels. The patient's blood glucose level was found to be 38 mg per deciliter, which is significantly below the normal range of 70 to 110 mg per deciliter. The patient's symptoms resolved after administration of a glucose solution, further supporting the diagnosis of hypoglycemia.\n\nDiagnosis: Hypoglycemia.""
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10.1056/NEJMcpc1802826,"Case 22-2018: A 64-Year-Old Man with Progressive Leg Weakness, Recurrent Falls, and Anemia","Hematocrit (%)   36.1
Hemoglobin (g/dl)   12.7
White-cell count (per mm3)   6090
Differential count (%)
Neutrophils   69
Lymphocytes   18
Monocytes   12
Eosinophils   0.5
Basophils   0.3
Platelet count (per mm3
)   236,000
Red-cell count (per mm3
)   3,970,000
Mean corpuscular volume (fl)   90.9
Mean corpuscular hemoglobin (pg) 26–34 32
Mean corpuscular hemoglobin level (g/dl) 31–37 35.2
Red-cell distribution width (%)   14.5
Reticulocyte count (%) 0.5–2.5 2.1
Erythrocyte sedimentation rate (mm/hr)   36
Sodium (mmol/liter)   126
Potassium (mmol/liter)   3.9
Chloride (mmol/liter)   83
Carbon dioxide (mmol/liter)   23
Glucose (mg/dl)   95
Urea nitrogen (mg/dl)   14
Creatinine (mg/dl)   1.1
Prothrombin time (sec) 11–14 15.2
Prothrombin-time international normalized ratio   1.2
Alkaline phosphatase (U/liter)   142
Bilirubin (mg/dl)
Total 0–1.0 1.3
Direct   0.5
Alanine aminotransferase (U/liter)   58
Aspartate aminotransferase (U/liter)   79
Osmolality in blood (mOsm/kg of water) 28 96 263
Osmolality in random urine (mOsm/kg of water) 15 50 153
Sodium in random urine (mmol/liter) NA  ","Vitamin C deficiency (scurvy). Vitamin B6, folate, zinc, and selenium deficiencies. Alcohol-use disorder.",Vitamin C deficiency (scurvy).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old man was admitted to this hospital because of progressive leg weakness, recurrent falls, and anemia.
The patient had been in his usual state of health until 8 months before this admission, when fatigue on exertion and subjective leg weakness developed. During the next 3 months, the distance he was able to walk became progressively shorter, because he frequently needed to stop and rest owing to fatigue and leg weakness; he had previously been able to walk long distances. Five months before this admission, intermittent hypoesthesias and paresthesias developed in the feet. Four months before this admission, two lower teeth became loose and fell out, with no preceding trauma.
Four months before this admission, the patient fell in his garage and attributed the fall to tripping over an object on the ground. He did not hit his head, lose consciousness, or need assistance to stand or walk after the fall. He was evaluated by his primary care provider. On evaluation, he reported 3 months of increased alcohol consumption (up to 6 or 7 glasses of wine each night) and several months of voluntarily restricted food intake to achieve weight loss. On physical examination, the vital signs were normal. The height was 166.6 cm, and the weight was 128.4 kg (6 months earlier, the weight had been 140.6 kg); the body-mass index (the weight in kilograms divided by the square of the height in meters) was 46. Ecchymoses were present on the knees. Two lower front teeth were absent, and there were areas of gingival bleeding; the remainder of the physical examination was normal. The patient was counseled on unhealthy alcohol use, but he declined a referral to an outpatient alcohol-cessation program.
During the next 4 months, fatigue and leg weakness gradually progressed, and the patient needed to use his arms to rise from a seated position. He had three additional falls, which he described as his legs ""giving out"" while he was walking. Two days before admission, the patient fell while he was carrying a bag of groceries and struck the left side of his face on the ground. With each fall, there was no loss of consciousness or associated light-headedness, dizziness, chest pain, dyspnea, palpitations, nausea, or incontinence. The patient rented a wheelchair to avoid walking long distances and presented to his primary care clinic at this hospital for evaluation.
On evaluation in the clinic, the patient reported mild pain above the left eye but no headache, neck pain, back pain, urinary retention, fecal incontinence, fever, chills, morning stiffness, muscle pain, muscle swelling, dark stools, melena, or hematemesis. He had a history of atrial fibrillation, hypertension, gout, osteoarthritis of the knees, gastroesophageal reflux disease, and Barrett's esophagus, which had been diagnosed by means of biopsy 7 years before this admission. Roux-en-Y gastric bypass had been performed 6 years before this admission. Medications were allopurinol, amlodipine, furosemide, indomethacin, losartan, metoprolol, omeprazole, rivaroxaban, bupropion, cyanocobalamin, ergocalciferol, and a thiamine supplement. The patient was divorced, lived alone, and worked as a store manager. He did not smoke tobacco. His father and brother had both died of esophageal cancer.
On evaluation in the clinic, the temperature was 36.3[degrees]C, the blood pressure 139/81 mm Hg, the pulse 98 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 124.3 kg. Purple ecchymoses were present on the left side of the face and left flank, and brown ecchymoses were present around the right eye. Two lower front teeth were absent (Figure 1A). The first and second heart sounds were normal, without murmurs. The breath sounds were normal bilaterally, without wheezing or rhonchi. Bowel sounds were present, and the abdomen was soft, nondistended, and nontender on palpation. The edge of the liver was not palpable, and the spleen was not enlarged. Motor strength was 3 out of 5 bilaterally on hip flexion and 4 out of 5 bilaterally on hip extension; the patient could not rise from a seated position, even when he used his arms for assistance. The remainder of the motor examination was normal. There was no muscle atrophy, swelling, or tenderness on palpation. Perception of pinprick was diminished in the legs from the toes to above the knees. Perception of light touch was diminished on the plantar surface of the feet. Proprioception was decreased in the big toes. Reflexes were normal, as were the results of finger-nose-finger testing. An evaluation for the Babinski sign and a Romberg test were not performed. Hair was thin and fragile on the arms and absent on the legs. The stool was brown and negative for occult blood. The remainder of the physical examination was normal. The patient was referred to the emergency department of this hospital for further evaluation.	
Figure 1
In the emergency department, laboratory evaluation revealed normal blood levels of calcium, phosphorus, magnesium, total protein, albumin, troponin T, creatine kinase, vitamin B12, 1,25-dihydroxyvitamin D, thyrotropin, and glycated hemoglobin. Urinalysis revealed a specific gravity of 1.009 (reference range, 1.001 to 1.035), a pH of 5 (reference range, 5 to 9), and ketones, with no protein, glucose, bilirubin, or blood. Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and HIV type 1 and type 2 antibodies were negative; other laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
Computed tomography of the head, performed without the administration of intravenous contrast material, revealed soft-tissue swelling on the left anterior side of the face, with no evidence of fracture, intracranial hemorrhage, infarction, hydrocephalus, or mass lesion. A chest radiograph showed degenerative changes of the bony thorax, with no evidence of pneumonia or pulmonary edema.
The patient was admitted to the hospital, and a high-dose thiamine infusion, a folate supplement, and a multivitamin were administered, in addition to his usual medications. One hour after admission, the blood pressure was 89/47 mm Hg and the heart rate was 90 beats per minute while the patient was sitting; after he stood up, the blood pressure was 75/40 mm Hg and the heart rate was 100 beats per minute. Amlodipine, furosemide, losartan, and metoprolol were discontinued, and fluids were administered intravenously. Two days later, the blood pressure was 124/72 and the heart rate was 91 beats per minute while the patient was sitting; after he stood up, the blood pressure was 80/50 mm Hg and the heart rate was 89 beats per minute. He could rise from a seated position with minimal use of his arms. An area of bruising (10 cm in diameter) developed on the right forearm, where a peripheral intravenous catheter had been placed (Figure 1B).
A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 64-year-old man was admitted to this hospital because of progressive leg weakness, recurrent falls, and anemia.
The patient had been in his usual state of health until 8 months before this admission, when fatigue on exertion and subjective leg weakness developed. During the next 3 months, the distance he was able to walk became progressively shorter, because he frequently needed to stop and rest owing to fatigue and leg weakness; he had previously been able to walk long distances. Five months before this admission, intermittent hypoesthesias and paresthesias developed in the feet. Four months before this admission, two lower teeth became loose and fell out, with no preceding trauma.
Four months before this admission, the patient fell in his garage and attributed the fall to tripping over an object on the ground. He did not hit his head, lose consciousness, or need assistance to stand or walk after the fall. He was evaluated by his primary care provider. On evaluation, he reported 3 months of increased alcohol consumption (up to 6 or 7 glasses of wine each night) and several months of voluntarily restricted food intake to achieve weight loss. On physical examination, the vital signs were normal. The height was 166.6 cm, and the weight was 128.4 kg (6 months earlier, the weight had been 140.6 kg); the body-mass index (the weight in kilograms divided by the square of the height in meters) was 46. Ecchymoses were present on the knees. Two lower front teeth were absent, and there were areas of gingival bleeding; the remainder of the physical examination was normal. The patient was counseled on unhealthy alcohol use, but he declined a referral to an outpatient alcohol-cessation program.
During the next 4 months, fatigue and leg weakness gradually progressed, and the patient needed to use his arms to rise from a seated position. He had three additional falls, which he described as his legs ""giving out"" while he was walking. Two days before admission, the patient fell while he was carrying a bag of groceries and struck the left side of his face on the ground. With each fall, there was no loss of consciousness or associated light-headedness, dizziness, chest pain, dyspnea, palpitations, nausea, or incontinence. The patient rented a wheelchair to avoid walking long distances and presented to his primary care clinic at this hospital for evaluation.
On evaluation in the clinic, the patient reported mild pain above the left eye but no headache, neck pain, back pain, urinary retention, fecal incontinence, fever, chills, morning stiffness, muscle pain, muscle swelling, dark stools, melena, or hematemesis. He had a history of atrial fibrillation, hypertension, gout, osteoarthritis of the knees, gastroesophageal reflux disease, and Barrett's esophagus, which had been diagnosed by means of biopsy 7 years before this admission. Roux-en-Y gastric bypass had been performed 6 years before this admission. Medications were allopurinol, amlodipine, furosemide, indomethacin, losartan, metoprolol, omeprazole, rivaroxaban, bupropion, cyanocobalamin, ergocalciferol, and a thiamine supplement. The patient was divorced, lived alone, and worked as a store manager. He did not smoke tobacco. His father and brother had both died of esophageal cancer.
On evaluation in the clinic, the temperature was 36.3[degrees]C, the blood pressure 139/81 mm Hg, the pulse 98 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 124.3 kg. Purple ecchymoses were present on the left side of the face and left flank, and brown ecchymoses were present around the right eye. Two lower front teeth were absent (Figure 1A). The first and second heart sounds were normal, without murmurs. The breath sounds were normal bilaterally, without wheezing or rhonchi. Bowel sounds were present, and the abdomen was soft, nondistended, and nontender on palpation. The edge of the liver was not palpable, and the spleen was not enlarged. Motor strength was 3 out of 5 bilaterally on hip flexion and 4 out of 5 bilaterally on hip extension; the patient could not rise from a seated position, even when he used his arms for assistance. The remainder of the motor examination was normal. There was no muscle atrophy, swelling, or tenderness on palpation. Perception of pinprick was diminished in the legs from the toes to above the knees. Perception of light touch was diminished on the plantar surface of the feet. Proprioception was decreased in the big toes. Reflexes were normal, as were the results of finger-nose-finger testing. An evaluation for the Babinski sign and a Romberg test were not performed. Hair was thin and fragile on the arms and absent on the legs. The stool was brown and negative for occult blood. The remainder of the physical examination was normal. The patient was referred to the emergency department of this hospital for further evaluation.	
Figure 1
In the emergency department, laboratory evaluation revealed normal blood levels of calcium, phosphorus, magnesium, total protein, albumin, troponin T, creatine kinase, vitamin B12, 1,25-dihydroxyvitamin D, thyrotropin, and glycated hemoglobin. Urinalysis revealed a specific gravity of 1.009 (reference range, 1.001 to 1.035), a pH of 5 (reference range, 5 to 9), and ketones, with no protein, glucose, bilirubin, or blood. Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and HIV type 1 and type 2 antibodies were negative; other laboratory test results are shown in Table 1. Imaging studies were obtained.	
Table 1 
Computed tomography of the head, performed without the administration of intravenous contrast material, revealed soft-tissue swelling on the left anterior side of the face, with no evidence of fracture, intracranial hemorrhage, infarction, hydrocephalus, or mass lesion. A chest radiograph showed degenerative changes of the bony thorax, with no evidence of pneumonia or pulmonary edema.
The patient was admitted to the hospital, and a high-dose thiamine infusion, a folate supplement, and a multivitamin were administered, in addition to his usual medications. One hour after admission, the blood pressure was 89/47 mm Hg and the heart rate was 90 beats per minute while the patient was sitting; after he stood up, the blood pressure was 75/40 mm Hg and the heart rate was 100 beats per minute. Amlodipine, furosemide, losartan, and metoprolol were discontinued, and fluids were administered intravenously. Two days later, the blood pressure was 124/72 and the heart rate was 91 beats per minute while the patient was sitting; after he stood up, the blood pressure was 80/50 mm Hg and the heart rate was 89 beats per minute. He could rise from a seated position with minimal use of his arms. An area of bruising (10 cm in diameter) developed on the right forearm, where a peripheral intravenous catheter had been placed (Figure 1B).
A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of progressive leg weakness, recurrent falls, anemia, and tooth loss, along with his history of increased alcohol consumption and restricted food intake, suggest a nutritional deficiency. The presence of hypoesthesia and paresthesia in the feet, diminished perception of pinprick and light touch, and decreased proprioception in the big toes suggest peripheral neuropathy, which can be caused by vitamin B12 deficiency. However, the patient's vitamin B12 levels were normal. The patient's history of gastric bypass surgery increases his risk for nutritional deficiencies, particularly of fat-soluble vitamins and minerals. The patient's ecchymoses and gingival bleeding suggest a coagulopathy, which can be caused by vitamin K deficiency. However, vitamin K deficiency would not explain the patient's neurological symptoms. The patient's symptoms, history, and physical examination findings are consistent with a diagnosis of scurvy, which is caused by vitamin C deficiency. Scurvy can cause weakness, anemia, tooth loss, and bleeding problems, including ecchymoses and gingival bleeding. The patient's history of restricted food intake and increased alcohol consumption, along with his history of gastric bypass surgery, increase his risk for vitamin C deficiency.\n\nDiagnosis: Scurvy (Vitamin C deficiency)""
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        ""content"": ""The patient's symptoms of progressive leg weakness, recurrent falls, anemia, and tooth loss, along with the presence of ecchymoses and thin, fragile hair, suggest a nutritional deficiency. The patient's history of increased alcohol consumption and restricted food intake for weight loss further supports this. The patient's history of gastric bypass surgery could have led to malabsorption of nutrients. The patient's symptoms improved with the administration of high-dose thiamine, folate, and a multivitamin, suggesting that these deficiencies were the cause of his symptoms. The patient's symptoms and their improvement with supplementation suggest a diagnosis of nutritional deficiency, specifically scurvy due to vitamin C deficiency. Scurvy can cause weakness, anemia, tooth loss, and easy bruising, all of which were present in this patient.\n\nDiagnosis: Scurvy due to Vitamin C deficiency.""
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}",Scurvy due to Vitamin C deficiency,Y,"{
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        ""content"": ""The patient is a 64-year-old man presenting with progressive leg weakness, recurrent falls, and anemia. He also reports fatigue on exertion, subjective leg weakness, intermittent hypoesthesias and paresthesias in the feet, and tooth loss. He has a history of increased alcohol consumption and restricted food intake for weight loss. His physical examination reveals ecchymoses on the knees and areas of gingival bleeding. His motor strength is diminished, particularly in the hip flexion and extension, and he has decreased perception of pinprick in the legs and light touch on the plantar surface of the feet. His proprioception is also decreased in the big toes. His hair is thin and fragile on the arms and absent on the legs. His laboratory evaluation reveals normal levels of calcium, phosphorus, magnesium, total protein, albumin, troponin T, creatine kinase, vitamin B12, 1,25-dihydroxyvitamin D, thyrotropin, and glycated hemoglobin. His urinalysis reveals ketones, with no protein, glucose, bilirubin, or blood. His blood tests for HIV type 1 p24 antigen and HIV type 1 and type 2 antibodies are negative. \n\nThe differential diagnosis for this patient includes alcoholic neuropathy, malnutrition, vitamin deficiencies (particularly B vitamins), and peripheral neuropathy due to other causes such as diabetes or autoimmune diseases. The patient's history of increased alcohol consumption and restricted food intake, along with his symptoms of leg weakness, paresthesias, and decreased proprioception, are suggestive of alcoholic neuropathy. His tooth loss and gingival bleeding could be due to vitamin C deficiency, while his anemia could be due to vitamin B12 or folate deficiency. However, his laboratory evaluation reveals normal levels of these vitamins. His thin and fragile hair could be due to malnutrition or vitamin deficiencies. His negative HIV tests rule out HIV-associated neuropathy. \n\nGiven the patient's history of increased alcohol consumption and restricted food intake, along with his symptoms and the absence of other causes in his laboratory evaluation, the most likely diagnosis is alcoholic neuropathy.\n\nDiagnosis: Alcoholic neuropathy.""
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}",Alcoholic neuropathy,N
10.1056/NEJMcpc1712229,"Case 21-2018: A 61-Year-Old Man with Grandiosity, Impulsivity, and Decreased Sleep","Hematocrit (%)   44.4
Hemoglobin (g/dl)   15.2
Mean corpuscular volume (fl)   95.3
White-cell count (per mm3
)   7840
Platelet count (per mm3
)   192,000
Sodium (mmol/liter)   142
Potassium (mmol/liter)   4.3
Chloride (mmol/liter)   94
Carbon dioxide (mmol/liter)   33
Urea nitrogen (mg/dl)   17
Creatinine (mg/dl)   0.73
Glucose (mg/dl)   116
N-terminal pro–B-type natriuretic peptide (pg/ml)   878
Troponin T (ng/ml) <0.03  
Thyrotropin (μIU/ml) 0.4 0 1.60
Albumin (g/dl)   3.2
Cholesterol (mg/dl)
Total <200 139
Low-density lipoprotein   64
High-density lipoprotein   57
Triglycerides (mg/dl)   91
Erythrocyte sedimentation rate (mm/hr)   29
C-reactive protein (mg/liter)  .0 11.1
Vitamin B12 (pg/ml) >250 446
Antitreponemal antibody Nonreactive Nonreactive
Acetaminophen (μg/ml) 10. 5.0 <5.0
Salicylates (mg/dl) 10. 0.0 <3.0
Ethanol (mg/dl) Negative Negative
Tricyclic antidepressants Negative Negative
Urine
Urine toxicology screen Negative for amphetamines, 
barbiturates, benzodiaz‚Äë
epines, cannabinoids, 
cocaine, opiates, phen‚Äë
cyclidine
Negative",Poststroke mania and the frontal lobe syndrome.,Poststroke mania and the frontal lobe syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 61-year-old man was brought to the emergency department of this hospital by his family because of concerns about grandiosity, impulsivity, decreased sleep, and increased alcohol use.
The patient had a history of alcohol-use disorder; he had started drinking heavily in his 20s. Sixteen years before this presentation, he was involved in a high-speed motor vehicle accident. He was admitted to this hospital because of multiple traumatic rib fractures with pneumothoraxes. An evaluation was notable for a serum ethanol level of 2659 mg per liter (reference range,  00), a creatine kinase level of 670 U per liter (reference range, 60 to 400), and an aspartate aminotransferase level of 95 U per liter (reference range, 10 to 40); a comprehensive urine and serum toxicology screen was otherwise negative. Bilateral chest tubes were placed for the pneumothoraxes. The patient was evaluated by psychiatry and addiction consultants, but longitudinal follow-up was not maintained.
Eight years before this presentation, the patient was evaluated for an episode of severe depression; an unspecified antidepressant medication was prescribed, but he declined to follow up with psychiatry. Four years before this presentation, during a period in which he reportedly felt impulsive, he was arrested three times within 2 weeks for driving under the influence of alcohol; he was sentenced to jail and was forced to surrender his driver's license. Thereafter, he abstained from drinking alcohol and participated in an intensive outpatient program and Alcoholics Anonymous. He was referred to a psychiatrist for persistent severe depression, but he declined to attend the appointments. His primary care physician initiated several trials of antidepressants, including selective serotonin-reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, but the treatments had no clear benefit.
One year before this presentation, the patient was admitted to a second hospital after he had a fall in the context of acute weakness and numbness of an arm and leg. Magnetic resonance imaging (MRI) of the head reportedly revealed evidence of remote infarcts of the right frontal and left parietal lobes, as well as diffuse white-matter disease. Aspirin, atorvastatin, and duloxetine were prescribed. On discharge, there were no residual neurologic deficits.
Three months before this presentation, after 3.5 years of sobriety, the patient began to drink 1 pint of vodka per day. A few days after resuming alcohol intake, the patient noted dyspnea and presented to the second hospital, where atrial flutter was detected. Transesophageal echocardiography revealed moderate left ventricular systolic dysfunction, mild-to-moderate mitral regurgitation, a patent foramen ovale, and no evidence of thrombus in the left atrial appendage. Direct-current cardioversion was performed, resulting in sinus rhythm. Aspirin and duloxetine were discontinued, and therapy with apixaban, torsemide, lisinopril, and metoprolol tartrate was initiated.
The next month, during a period in which the patient reportedly felt reckless and out of control, he borrowed his wife's car and drove for the first time since surrendering his license. He lost control of the car and crashed into a barn, sustaining spinal fractures that necessitated the use of a cane. During the same period, the patient was also noted to spend impulsively, to need less sleep, and to be increasingly physically and verbally abusive toward family members. He was seen by his primary care physician, who thought that his affect was manic, representing a marked change from his baseline of depression.
One month before this presentation, the patient reportedly had increased energy, irritability, a euphoric mood, and a decreased need to sleep. He was spending impulsively, including $25,000 on home renovations that were viewed to be unnecessary by his family. The patient increased his consumption to more than 1 pint of vodka daily. He was evaluated by a psychiatrist at another institution, and a diagnosis of bipolar disorder was considered. Lurasidone was prescribed, but the patient took it for only 10 days.
Three days before this presentation, the patient traveled to Boston by bus and taxi from his home state. He checked into several hotels, gambled, shopped extravagantly, and invited strangers for a steak dinner. He ran out of money and contacted friends and family in Boston, including his son, for money. Although the patient threatened to assault his son, his son brought him to the emergency department at this hospital.
On presentation, history was obtained from the patient, as well as his wife and son. The patient reported having a high energy level and racing thoughts and needing to sleep only 3 hours per night. He had no weakness, numbness, vision changes, headache, dysarthria, dysphagia, or hallucinations. He reported no fever, abdominal pain, chest pain, palpitations, or dyspnea. He had not had a previous psychiatric hospitalization. The medical history was notable for stroke, atrial dysrhythmia, hypertension, dyslipidemia, and remote migraines. Medications on presentation were apixaban, atorvastatin, torsemide, lisinopril, and metoprolol tartrate. There was no history of adverse reactions to medications.
The patient's father had had one psychiatric hospitalization for an unclear diagnosis and had died of stomach cancer; the patient's brother had schizophrenia, and his mother had died of heart failure. There was no family history of substance-use disorder, stroke, or suicide. The patient reported no illicit-drug use and had smoked 1 to 2 packs of cigarettes daily for 40 years. He had been born and raised in the Boston area and had completed community college before working as a sales manager. He lived with his wife in New England and had two adult children living near Boston.
On examination, the temperature was 36.4[degrees]C, the heart rate 78 beats per minute, the blood pressure 175/90 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. He was described as agitated and belligerent, with some pressured and rapid but interruptible speech. He had a ruddy complexion and mild, symmetric pitting edema of the legs. The results of a comprehensive neurologic examination were normal, except for the presence of mild dysmetria on bilateral finger-nose-finger tests and a low-amplitude action tremor. A mental status examination was notable for impaired short-term recall and tangential answers to questions. The patient was described as having an expansive mood, with some emotional lability, including intermittent tearfulness.
Results of urinalysis, chest radiography, and liver-function tests were normal, as were blood levels of calcium, magnesium, phosphorus, total protein, and lipase. Other laboratory test results are shown in Table 1. Transthoracic echocardiography revealed left ventricular dilatation and dysfunction (ejection fraction, 38%), right ventricular hypokinesis, biatrial dilatation, a patent foramen ovale with an interatrial septal aneurysm, aortic-valve sclerosis, and mild mitral regurgitation.	
Table 1 
The patient was admitted to the hospital, and a diagnosis was made
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
A 61-year-old man was brought to the emergency department of this hospital by his family because of concerns about grandiosity, impulsivity, decreased sleep, and increased alcohol use.
The patient had a history of alcohol-use disorder; he had started drinking heavily in his 20s. Sixteen years before this presentation, he was involved in a high-speed motor vehicle accident. He was admitted to this hospital because of multiple traumatic rib fractures with pneumothoraxes. An evaluation was notable for a serum ethanol level of 2659 mg per liter (reference range,  00), a creatine kinase level of 670 U per liter (reference range, 60 to 400), and an aspartate aminotransferase level of 95 U per liter (reference range, 10 to 40); a comprehensive urine and serum toxicology screen was otherwise negative. Bilateral chest tubes were placed for the pneumothoraxes. The patient was evaluated by psychiatry and addiction consultants, but longitudinal follow-up was not maintained.
Eight years before this presentation, the patient was evaluated for an episode of severe depression; an unspecified antidepressant medication was prescribed, but he declined to follow up with psychiatry. Four years before this presentation, during a period in which he reportedly felt impulsive, he was arrested three times within 2 weeks for driving under the influence of alcohol; he was sentenced to jail and was forced to surrender his driver's license. Thereafter, he abstained from drinking alcohol and participated in an intensive outpatient program and Alcoholics Anonymous. He was referred to a psychiatrist for persistent severe depression, but he declined to attend the appointments. His primary care physician initiated several trials of antidepressants, including selective serotonin-reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, but the treatments had no clear benefit.
One year before this presentation, the patient was admitted to a second hospital after he had a fall in the context of acute weakness and numbness of an arm and leg. Magnetic resonance imaging (MRI) of the head reportedly revealed evidence of remote infarcts of the right frontal and left parietal lobes, as well as diffuse white-matter disease. Aspirin, atorvastatin, and duloxetine were prescribed. On discharge, there were no residual neurologic deficits.
Three months before this presentation, after 3.5 years of sobriety, the patient began to drink 1 pint of vodka per day. A few days after resuming alcohol intake, the patient noted dyspnea and presented to the second hospital, where atrial flutter was detected. Transesophageal echocardiography revealed moderate left ventricular systolic dysfunction, mild-to-moderate mitral regurgitation, a patent foramen ovale, and no evidence of thrombus in the left atrial appendage. Direct-current cardioversion was performed, resulting in sinus rhythm. Aspirin and duloxetine were discontinued, and therapy with apixaban, torsemide, lisinopril, and metoprolol tartrate was initiated.
The next month, during a period in which the patient reportedly felt reckless and out of control, he borrowed his wife's car and drove for the first time since surrendering his license. He lost control of the car and crashed into a barn, sustaining spinal fractures that necessitated the use of a cane. During the same period, the patient was also noted to spend impulsively, to need less sleep, and to be increasingly physically and verbally abusive toward family members. He was seen by his primary care physician, who thought that his affect was manic, representing a marked change from his baseline of depression.
One month before this presentation, the patient reportedly had increased energy, irritability, a euphoric mood, and a decreased need to sleep. He was spending impulsively, including $25,000 on home renovations that were viewed to be unnecessary by his family. The patient increased his consumption to more than 1 pint of vodka daily. He was evaluated by a psychiatrist at another institution, and a diagnosis of bipolar disorder was considered. Lurasidone was prescribed, but the patient took it for only 10 days.
Three days before this presentation, the patient traveled to Boston by bus and taxi from his home state. He checked into several hotels, gambled, shopped extravagantly, and invited strangers for a steak dinner. He ran out of money and contacted friends and family in Boston, including his son, for money. Although the patient threatened to assault his son, his son brought him to the emergency department at this hospital.
On presentation, history was obtained from the patient, as well as his wife and son. The patient reported having a high energy level and racing thoughts and needing to sleep only 3 hours per night. He had no weakness, numbness, vision changes, headache, dysarthria, dysphagia, or hallucinations. He reported no fever, abdominal pain, chest pain, palpitations, or dyspnea. He had not had a previous psychiatric hospitalization. The medical history was notable for stroke, atrial dysrhythmia, hypertension, dyslipidemia, and remote migraines. Medications on presentation were apixaban, atorvastatin, torsemide, lisinopril, and metoprolol tartrate. There was no history of adverse reactions to medications.
The patient's father had had one psychiatric hospitalization for an unclear diagnosis and had died of stomach cancer; the patient's brother had schizophrenia, and his mother had died of heart failure. There was no family history of substance-use disorder, stroke, or suicide. The patient reported no illicit-drug use and had smoked 1 to 2 packs of cigarettes daily for 40 years. He had been born and raised in the Boston area and had completed community college before working as a sales manager. He lived with his wife in New England and had two adult children living near Boston.
On examination, the temperature was 36.4[degrees]C, the heart rate 78 beats per minute, the blood pressure 175/90 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. He was described as agitated and belligerent, with some pressured and rapid but interruptible speech. He had a ruddy complexion and mild, symmetric pitting edema of the legs. The results of a comprehensive neurologic examination were normal, except for the presence of mild dysmetria on bilateral finger-nose-finger tests and a low-amplitude action tremor. A mental status examination was notable for impaired short-term recall and tangential answers to questions. The patient was described as having an expansive mood, with some emotional lability, including intermittent tearfulness.
Results of urinalysis, chest radiography, and liver-function tests were normal, as were blood levels of calcium, magnesium, phosphorus, total protein, and lipase. Other laboratory test results are shown in Table 1. Transthoracic echocardiography revealed left ventricular dilatation and dysfunction (ejection fraction, 38%), right ventricular hypokinesis, biatrial dilatation, a patent foramen ovale with an interatrial septal aneurysm, aortic-valve sclerosis, and mild mitral regurgitation.	
Table 1 
The patient was admitted to the hospital, and a diagnosis was made
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of grandiosity, impulsivity, decreased need for sleep, and increased alcohol use are indicative of a manic episode. His history of severe depression suggests that these manic episodes are part of a larger pattern of mood swings. This pattern of alternating depressive and manic episodes is characteristic of bipolar disorder. The patient's reckless behavior, such as driving without a license and spending impulsively, further supports this diagnosis. His symptoms did not improve with the use of antidepressants, which is common in cases of bipolar disorder as mood stabilizers or antipsychotics are often more effective. \n\nDiagnosis: Bipolar Disorder""
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        ""content"": ""The patient is a 61-year-old man with a history of alcohol-use disorder, depression, and stroke. He presents with grandiosity, impulsivity, decreased sleep, and increased alcohol use. The differential diagnosis for this patient includes bipolar disorder, alcohol-induced mood disorder, and a mood disorder due to a general medical condition. The patient's history of alcohol use disorder and recent increase in alcohol consumption could suggest an alcohol-induced mood disorder. However, the patient's symptoms persisted during periods of sobriety, making this diagnosis less likely. A mood disorder due to a general medical condition could also be considered given the patient's history of stroke and the presence of white-matter disease on MRI. However, the patient's symptoms are not clearly related to the timing of his stroke or to any other medical condition. The patient's symptoms of grandiosity, decreased need for sleep, and impulsivity, along with a history of severe depression, are most consistent with bipolar disorder. The patient's symptoms represent a marked change from his baseline depressive state and meet the criteria for a manic episode, which is necessary for a diagnosis of bipolar disorder. \n\nDiagnosis: Bipolar disorder.""
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10.1056/NEJMcpc1800334,"Case 20-2018: A 64-Year-Old Man with Fever, Arthralgias, and Testicular Pain",,Polyarteritis nodosa.,Polyarteritis nodosa.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 64-year-old man was admitted to this hospital with a 2-week history of fever, chills, arthralgias, abdominal and testicular pain, and leukocytosis.

Twenty-five years before the current admission, while the patient was living in China, he received a diagnosis of pulmonary tuberculosis. At that time, he completed a 14-month course of a four-drug regimen for tuberculosis (with unknown medications). Although the treatment was completed, a chronic cough that produced scant white sputum persisted. Two years later, the patient immigrated to the United States, and examination of an induced sputum sample for Mycobacterium tuberculosis was reportedly negative.

The patient also had a history of hepatitis B virus (HBV) infection; 12 years before the current admission, he had a positive test for HBV surface antigen. At that time, a nucleic acid amplification test for HBV DNA was negative. Thereafter, annual surveillance for cancer was performed with abdominal ultrasonography and measurement of the blood alpha-fetoprotein level. An elevated alpha-fetoprotein level was never detected. Ultrasonography was notable for the presence of simple hepatic and renal cysts and heterogeneous hepatic echotexture, but follow-up examination with magnetic resonance imaging (MRI) of the liver revealed no signal abnormality.

Three years before the current admission, the patient was evaluated for chronic cough. Radiography of the chest revealed a nodular opacity at the apex of the right lung. Follow-up examination with computed tomography (CT) of the chest revealed a calcified granuloma at the right apex and evidence of bronchiectasis, and plans were made for annual surveillance with CT.

Fourteen days before the current admission, anorexia and fatigue developed, along with pain and tightness in the back and calves. Six days later, the patient was seen by his primary care physician at this hospital. He reported no antecedent trauma. The temperature was 37.0°C. There was tenderness in the bilateral lumbar paraspinal muscles. Results of a neurologic examination — including tests of motor strength, sensation, reflexes, coordination, and gait — were normal. Radiography of the lumbar spine revealed multilevel degenerative disk disease that was most pronounced at the L4 to L5 level, with preserved vertebral-body height. Ibuprofen was prescribed.

Table 1.

Laboratory Data.
Later that day, the temperature reached 38.9°C. Fever, chills, sweats, and rigors persisted and were associated with myalgias of the back and calves that were severe enough to impair walking. Ibuprofen provided only temporary relief of the fever and myalgias. The patient visited a traditional Chinese doctor, who performed moxibustion (i.e., the application of burning dried mugwort directly to the body) and administered a cathartic agent, which had no effect. Left testicular pain and swelling developed, and the patient returned to his primary care physician 5 days after the previous visit. He reported no dysuria, hematuria, lymphadenopathy, headache, nuchal rigidity, or rash. The examination was notable for a temperature of 37.8°C shortly after the administration of ibuprofen, the presence of moxibustion marks on the upper back, and a swollen, tender area on the upper lateral aspect of the left testicle. Screening tests for Lyme disease and nucleic acid amplification tests for babesia, ehrlichia, and anaplasma DNA were negative; other laboratory test results are shown in Table 1. Blood and urine cultures and imaging studies were performed.

Dr. Aoife Kilcoyne: On ultrasonography of the scrotum, both testes had normal echotexture and normal Doppler flow, with no focal lesions. Bilateral subcentimeter epididymal cysts were identified. Radiography of the chest revealed a nodular opacity at the apex of the right lung, which had not changed from previous studies and was most likely related to previous granulomatous disease. There were new ill-defined opacities at the lung bases that, in the appropriate clinical context, could reflect multifocal pneumonia.

Dr. Schneider: A 7-day course of levofloxacin was prescribed. Fever recurred (with a temperature of up to 39.0°C) and was associated with chills, rigors, anorexia, myalgias, and arthralgias. These symptoms persisted for the next 3 days, and the myalgias and arthralgias appeared to worsen when the temperature was highest. The patient also had intermittent sharp abdominal pain, two episodes of nonbloody diarrhea, and a weight loss of 1 kg. His primary care physician referred him to the emergency department of this hospital.

Additional patient history was obtained in the emergency department. The patient reported brief, sharp, stabbing chest pain that was not related to exertion, as well as a chronic cough that produced thin, white sputum. He also noted that blurry vision had developed in the left eye 2 days earlier, with no vision loss. He had pruritus and tinea cruris. A review of systems was negative for headache, jaw claudication, other rashes, and joint pain. No sick contacts were reported.

Medications included levofloxacin, aspirin, nystatin powder, and triamcinolone cream. The use of tamsulosin had caused nasal discharge. The patient had smoked a half pack of cigarettes per day for more than 40 years, but he did not use illicit drugs. He drank one glass of wine per night, although he had previously consumed up to two drinks of whiskey daily. The patient had retired from restaurant work 2 years earlier, and his last international trip had been to China 3 years earlier. His father died from lung cancer at 71 years of age, and his mother died at 39 years of age from an unknown cause. The patient had six siblings, a son who had a hemangioma, and a daughter who had an irregular heartbeat. There was no family history of pulmonary, ocular, infectious, or rheumatologic diseases.

On examination, the temperature was 37.8°C and then rose to 38.3°C, the blood pressure 126/64 mm Hg, the heart rate 74 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. He was awake and alert, and he appeared somewhat fatigued. The eyes had no scleral icterus, and the oropharynx had no erythema, exudates, or ulcerations. The neck was supple, with a normal range of motion, and the spine and paraspinal muscles were nontender. There was no cervical or axillary lymphadenopathy. Auscultation revealed faint rales at the lung bases and scattered bilateral rhonchi and wheezes, with no cardiac murmur or rub. The bowel sounds were normal, and the abdomen was soft, nontender, and nondistended, with no rebound, guarding, or hepatosplenomegaly. There was no rash, joint deformity, erythema, warmth, swelling, effusion, or tenderness. The joints had full range of motion. The stool was guaiac-negative. Motor strength was normal and symmetric in the arms and legs, and distal pulses were intact.

The levels of troponin T, creatine kinase, lipase, lactate dehydrogenase, prostate-specific antigen, and thyrotropin were normal; other laboratory test results are shown in Table 1. Cultures of urine and blood were performed. A respiratory viral panel was negative for adenovirus, influenza virus, parainfluenza virus, and metapneumovirus. An electrocardiogram showed sinus rhythm with premature atrial beats and was otherwise normal. Additional imaging studies were obtained.

Dr. Kilcoyne: Radiography of the chest revealed persistent opacities at the lung bases and right apex. Contrast-enhanced CT of the abdomen and pelvis revealed mildly increased enhancement of the gallbladder wall, as well as pericholecystic fluid. These findings are nonspecific; in the absence of gallstones, they could occur in the context of volume overload or as manifestations of a systemic condition, such as chronic liver disease. Scattered subcentimeter hypodensities were present in the liver that most likely represented simple cysts. Bilateral small pleural effusions and trace peritoneal fluid were present. Ultrasonography of the right upper quadrant revealed thickening of the gallbladder wall, along with gallbladder sludge. Sonographic Murphy’s sign was negative.

Table 2.

Additional Laboratory Data.
Dr. Schneider: The patient was admitted to the hospital. Levofloxacin was discontinued, and acetaminophen and one dose of doxycycline were administered. Over the next 6 days, the patient remained febrile, with a temperature ranging from 38.1 to 39.6°C. Additional tests were performed (Table 2). Hepatobiliary radionuclide scanning revealed patent cystic and common bile ducts, with no evidence of acute cholecystitis. Ophthalmologic evaluation revealed only mild cataracts and dry eyes, with no evidence of an eye infection or retinopathy.

Dr. Kilcoyne: Contrast-enhanced CT of the chest, performed on the fifth hospital day, revealed bilateral pleural effusions that were larger than they had been on the day of admission. Gadolinium-enhanced MRI of the cervical, thoracic, and lumbar spine revealed no evidence of diskitis, osteomyelitis, or epidural abscesses. Gadolinium-enhanced MRI of the liver revealed scattered subcentimeter simple hepatic cysts. Thoracentesis was performed on the right side with the use of ultrasonographic guidance.

Dr. Schneider: The pleural fluid was consistent with a transudative effusion. A test of the pleural fluid for adenosine deaminase was negative, as was a Gram’s stain and an acid-fast smear; cultures for bacteria, mycobacteria, and fungi were performed. Cytologic examination of the urine, which was performed because of the history of smoking and microscopic hematuria, revealed no malignant cells. Transthoracic echocardiography and transesophageal echocardiography revealed no valvular vegetation.

On the seventh hospital day, swelling, pain, and tenderness recurred in the left scrotum. The temperature reached 40.1°C. Urinalysis revealed 2+ blood and 10 to 20 red cells per high-power field.

Figure 1.

Ultrasound Images of the Scrotum.
Dr. Kilcoyne: Follow-up ultrasonography of the scrotum (Figure 1), performed 10 days after the first ultrasound study had been obtained, revealed new engorgement of testicular vessels that was greater on the left side than on the right side. Both testes were heterogeneous in echotexture. The findings were suggestive of epididymo-orchitis.

Dr. Schneider: Ceftriaxone was administered, and additional diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 64-year-old man was admitted to this hospital with a 2-week history of fever, chills, arthralgias, abdominal and testicular pain, and leukocytosis.

Twenty-five years before the current admission, while the patient was living in China, he received a diagnosis of pulmonary tuberculosis. At that time, he completed a 14-month course of a four-drug regimen for tuberculosis (with unknown medications). Although the treatment was completed, a chronic cough that produced scant white sputum persisted. Two years later, the patient immigrated to the United States, and examination of an induced sputum sample for Mycobacterium tuberculosis was reportedly negative.

The patient also had a history of hepatitis B virus (HBV) infection; 12 years before the current admission, he had a positive test for HBV surface antigen. At that time, a nucleic acid amplification test for HBV DNA was negative. Thereafter, annual surveillance for cancer was performed with abdominal ultrasonography and measurement of the blood alpha-fetoprotein level. An elevated alpha-fetoprotein level was never detected. Ultrasonography was notable for the presence of simple hepatic and renal cysts and heterogeneous hepatic echotexture, but follow-up examination with magnetic resonance imaging (MRI) of the liver revealed no signal abnormality.

Three years before the current admission, the patient was evaluated for chronic cough. Radiography of the chest revealed a nodular opacity at the apex of the right lung. Follow-up examination with computed tomography (CT) of the chest revealed a calcified granuloma at the right apex and evidence of bronchiectasis, and plans were made for annual surveillance with CT.

Fourteen days before the current admission, anorexia and fatigue developed, along with pain and tightness in the back and calves. Six days later, the patient was seen by his primary care physician at this hospital. He reported no antecedent trauma. The temperature was 37.0°C. There was tenderness in the bilateral lumbar paraspinal muscles. Results of a neurologic examination — including tests of motor strength, sensation, reflexes, coordination, and gait — were normal. Radiography of the lumbar spine revealed multilevel degenerative disk disease that was most pronounced at the L4 to L5 level, with preserved vertebral-body height. Ibuprofen was prescribed.

Table 1.

Laboratory Data.
Later that day, the temperature reached 38.9°C. Fever, chills, sweats, and rigors persisted and were associated with myalgias of the back and calves that were severe enough to impair walking. Ibuprofen provided only temporary relief of the fever and myalgias. The patient visited a traditional Chinese doctor, who performed moxibustion (i.e., the application of burning dried mugwort directly to the body) and administered a cathartic agent, which had no effect. Left testicular pain and swelling developed, and the patient returned to his primary care physician 5 days after the previous visit. He reported no dysuria, hematuria, lymphadenopathy, headache, nuchal rigidity, or rash. The examination was notable for a temperature of 37.8°C shortly after the administration of ibuprofen, the presence of moxibustion marks on the upper back, and a swollen, tender area on the upper lateral aspect of the left testicle. Screening tests for Lyme disease and nucleic acid amplification tests for babesia, ehrlichia, and anaplasma DNA were negative; other laboratory test results are shown in Table 1. Blood and urine cultures and imaging studies were performed.

Dr. Aoife Kilcoyne: On ultrasonography of the scrotum, both testes had normal echotexture and normal Doppler flow, with no focal lesions. Bilateral subcentimeter epididymal cysts were identified. Radiography of the chest revealed a nodular opacity at the apex of the right lung, which had not changed from previous studies and was most likely related to previous granulomatous disease. There were new ill-defined opacities at the lung bases that, in the appropriate clinical context, could reflect multifocal pneumonia.

Dr. Schneider: A 7-day course of levofloxacin was prescribed. Fever recurred (with a temperature of up to 39.0°C) and was associated with chills, rigors, anorexia, myalgias, and arthralgias. These symptoms persisted for the next 3 days, and the myalgias and arthralgias appeared to worsen when the temperature was highest. The patient also had intermittent sharp abdominal pain, two episodes of nonbloody diarrhea, and a weight loss of 1 kg. His primary care physician referred him to the emergency department of this hospital.

Additional patient history was obtained in the emergency department. The patient reported brief, sharp, stabbing chest pain that was not related to exertion, as well as a chronic cough that produced thin, white sputum. He also noted that blurry vision had developed in the left eye 2 days earlier, with no vision loss. He had pruritus and tinea cruris. A review of systems was negative for headache, jaw claudication, other rashes, and joint pain. No sick contacts were reported.

Medications included levofloxacin, aspirin, nystatin powder, and triamcinolone cream. The use of tamsulosin had caused nasal discharge. The patient had smoked a half pack of cigarettes per day for more than 40 years, but he did not use illicit drugs. He drank one glass of wine per night, although he had previously consumed up to two drinks of whiskey daily. The patient had retired from restaurant work 2 years earlier, and his last international trip had been to China 3 years earlier. His father died from lung cancer at 71 years of age, and his mother died at 39 years of age from an unknown cause. The patient had six siblings, a son who had a hemangioma, and a daughter who had an irregular heartbeat. There was no family history of pulmonary, ocular, infectious, or rheumatologic diseases.

On examination, the temperature was 37.8°C and then rose to 38.3°C, the blood pressure 126/64 mm Hg, the heart rate 74 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. He was awake and alert, and he appeared somewhat fatigued. The eyes had no scleral icterus, and the oropharynx had no erythema, exudates, or ulcerations. The neck was supple, with a normal range of motion, and the spine and paraspinal muscles were nontender. There was no cervical or axillary lymphadenopathy. Auscultation revealed faint rales at the lung bases and scattered bilateral rhonchi and wheezes, with no cardiac murmur or rub. The bowel sounds were normal, and the abdomen was soft, nontender, and nondistended, with no rebound, guarding, or hepatosplenomegaly. There was no rash, joint deformity, erythema, warmth, swelling, effusion, or tenderness. The joints had full range of motion. The stool was guaiac-negative. Motor strength was normal and symmetric in the arms and legs, and distal pulses were intact.

The levels of troponin T, creatine kinase, lipase, lactate dehydrogenase, prostate-specific antigen, and thyrotropin were normal; other laboratory test results are shown in Table 1. Cultures of urine and blood were performed. A respiratory viral panel was negative for adenovirus, influenza virus, parainfluenza virus, and metapneumovirus. An electrocardiogram showed sinus rhythm with premature atrial beats and was otherwise normal. Additional imaging studies were obtained.

Dr. Kilcoyne: Radiography of the chest revealed persistent opacities at the lung bases and right apex. Contrast-enhanced CT of the abdomen and pelvis revealed mildly increased enhancement of the gallbladder wall, as well as pericholecystic fluid. These findings are nonspecific; in the absence of gallstones, they could occur in the context of volume overload or as manifestations of a systemic condition, such as chronic liver disease. Scattered subcentimeter hypodensities were present in the liver that most likely represented simple cysts. Bilateral small pleural effusions and trace peritoneal fluid were present. Ultrasonography of the right upper quadrant revealed thickening of the gallbladder wall, along with gallbladder sludge. Sonographic Murphy’s sign was negative.

Table 2.

Additional Laboratory Data.
Dr. Schneider: The patient was admitted to the hospital. Levofloxacin was discontinued, and acetaminophen and one dose of doxycycline were administered. Over the next 6 days, the patient remained febrile, with a temperature ranging from 38.1 to 39.6°C. Additional tests were performed (Table 2). Hepatobiliary radionuclide scanning revealed patent cystic and common bile ducts, with no evidence of acute cholecystitis. Ophthalmologic evaluation revealed only mild cataracts and dry eyes, with no evidence of an eye infection or retinopathy.

Dr. Kilcoyne: Contrast-enhanced CT of the chest, performed on the fifth hospital day, revealed bilateral pleural effusions that were larger than they had been on the day of admission. Gadolinium-enhanced MRI of the cervical, thoracic, and lumbar spine revealed no evidence of diskitis, osteomyelitis, or epidural abscesses. Gadolinium-enhanced MRI of the liver revealed scattered subcentimeter simple hepatic cysts. Thoracentesis was performed on the right side with the use of ultrasonographic guidance.

Dr. Schneider: The pleural fluid was consistent with a transudative effusion. A test of the pleural fluid for adenosine deaminase was negative, as was a Gram’s stain and an acid-fast smear; cultures for bacteria, mycobacteria, and fungi were performed. Cytologic examination of the urine, which was performed because of the history of smoking and microscopic hematuria, revealed no malignant cells. Transthoracic echocardiography and transesophageal echocardiography revealed no valvular vegetation.

On the seventh hospital day, swelling, pain, and tenderness recurred in the left scrotum. The temperature reached 40.1°C. Urinalysis revealed 2+ blood and 10 to 20 red cells per high-power field.

Figure 1.

Ultrasound Images of the Scrotum.
Dr. Kilcoyne: Follow-up ultrasonography of the scrotum (Figure 1), performed 10 days after the first ultrasound study had been obtained, revealed new engorgement of testicular vessels that was greater on the left side than on the right side. Both testes were heterogeneous in echotexture. The findings were suggestive of epididymo-orchitis.

Dr. Schneider: Ceftriaxone was administered, and additional diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Disseminated tuberculosis. The patient has a history of pulmonary tuberculosis and has been experiencing symptoms such as fever, chills, arthralgias, abdominal and testicular pain, and leukocytosis. His symptoms have not improved with antibiotics, suggesting that the cause may not be a typical bacterial infection. The patient's history of tuberculosis, along with his persistent cough and the finding of a nodular opacity in his lung, suggest that his tuberculosis may have reactivated and become disseminated, causing his systemic symptoms. The patient's testicular pain and swelling, along with the ultrasound findings, suggest epididymo-orchitis, which can be caused by disseminated tuberculosis. The patient's leukocytosis could also be a response to a systemic infection such as disseminated tuberculosis.""
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        ""content"": ""This is a 64-year-old man with a history of pulmonary tuberculosis and hepatitis B virus infection who presents with fever, chills, arthralgias, abdominal and testicular pain, and leukocytosis. His symptoms have been ongoing for 2 weeks. The differential diagnosis for this patient includes a recurrence of tuberculosis, a flare of hepatitis B, a new infection such as a urinary tract infection or epididymitis, or a malignancy. His history of pulmonary tuberculosis is notable, but his sputum sample was negative for Mycobacterium tuberculosis after he completed treatment. His hepatitis B surface antigen was positive, but his HBV DNA was negative, suggesting he is not currently infected. His symptoms do not seem to be consistent with a flare of hepatitis B. His testicular pain and swelling could be due to epididymitis, which is supported by the ultrasound findings. His leukocytosis could be due to an infection or a malignancy. However, his alpha-fetoprotein level was never elevated, which makes a liver malignancy less likely. His chest radiography revealed a nodular opacity at the apex of the right lung, which could be due to his previous tuberculosis infection or a new malignancy. However, the opacity did not change from previous studies, which makes a new malignancy less likely. His abdominal and testicular pain, along with his leukocytosis, are most consistent with an infection such as epididymitis.\n\nDiagnosis: Epididymitis.""
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10.1056/NEJMcpc1802827,Case 19-2018: A 15-Year-Old Girl with Acute Kidney Injury,,Atypical hemolytic–uremic syndrome.,"The hemolytic–uremic syndrome, probably atypical.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 15-year-old girl was admitted to this hospital during the summer because of acute kidney injury.

The patient had been well until 8 days before admission, when painful cramping in the lower abdomen and bloody diarrhea developed. Bowel movements occurred approximately every hour, and the patient was unable to sleep. She took ibuprofen but had no relief of the abdominal pain.

On the third day of illness, two episodes of nonbloody, nonbilious emesis occurred. The following day, the patient was seen by her primary care pediatrician. She reported that she felt fatigued and that the diarrhea, abdominal cramping, and vomiting had persisted; she had not had a fever. The results of a physical examination were normal. Stool samples were obtained for cultures for salmonella, shigella, campylobacter, aeromonas, plesiomonas, and Escherichia coli O157:H7, and antigen-detection tests were performed for rotavirus, giardia, and Clostridium difficile toxin. The patient was advised to stop taking ibuprofen, to take loperamide and acetaminophen as needed, and to drink an electrolyte-containing oral rehydration solution. During the next 3 days, the diarrhea resolved, but the patient continued to vomit several times each day and the abdominal cramping became localized to the epigastrium. The stool cultures and antigen-detection tests were negative. Her mother called the pediatrician’s office on the seventh day of illness, and ondansetron was prescribed.

The following morning, the patient returned to the pediatrician’s office because of persistent painful cramping in the epigastrium. On examination, she appeared mildly ill and slightly pale. The temperature was 36.5°C, and the pulse 98 beats per minute. The abdomen was soft, with normal bowel sounds and mild, diffuse tenderness and with no distention, masses, or guarding. The remainder of the examination was normal. Ranitidine and a probiotic were recommended. Two hours after this appointment, the patient’s mother called the office to report that the patient had vomited again; she was advised to take the patient to the emergency department at a local hospital for further evaluation and treatment.

Table 1.

Laboratory Data.
In the emergency department at the other hospital, the patient reported that the volume of urine output had decreased. On examination, she appeared slightly pale. The temperature was 36.9°C, the pulse 80 beats per minute, the blood pressure 111/69 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The remainder of the examination was unchanged. Laboratory test results are shown in Table 1. Imaging studies of the abdomen were performed.

Figure 1.

Abdominal Ultrasound Images.
Dr. Pallavi Sagar: An abdominal radiograph was normal. Abdominal ultrasonography revealed a large amount of layering sludge in the gallbladder, with no thickening of the gallbladder wall (Figure 1A). Both kidneys were normal in size (length of the right kidney, 11.5 cm; length of the left kidney, 10.6 cm), with mildly echogenic renal parenchyma (Figure 1B and 1C). The urinary tract was not dilated, and the bladder was partially distended. A moderate amount of ascites was present in the lower abdomen, and a trace amount was present in Morison’s pouch (Figure 1D).

Dr. Healy: Two liters of normal saline were administered intravenously; afterward, the patient did not have any urine output. After consultation with a pediatric nephrologist, the patient was transferred to the emergency department at this hospital.

On arrival, the patient rated her abdominal pain at 3 on a scale of 0 to 10, with 10 indicating the most severe pain. She reported that, during the past week, her weight had decreased by 3 kg and then increased by 1 kg. She had a history of attention deficit–hyperactivity disorder, anxiety, and labial adhesions. During the previous 7 months, she had been seen by her pediatrician on three occasions because of intermittent dysuria; tests for urinary tract infection, chlamydia, and gonorrhea had been negative. Medications included citalopram and methylphenidate; she had an allergy to azithromycin, which had caused a rash. The patient lived with her parents and siblings in New England. Just before the onset of the current illness, she had spent several days in New York City, where she had eaten food purchased from street vendors. She had had no known exposure to sick persons, was not sexually active, and did not smoke cigarettes, drink alcohol, or use illicit drugs. Her maternal grandfather had the antiphospholipid syndrome, her paternal grandmother had hypothyroidism, and her mother had had gestational hypertension; there was no known family history of kidney disease or inflammatory bowel disease.

On examination, the patient appeared tired but otherwise well. The temperature was 36.9°C, the pulse 71 beats per minute, the blood pressure 124/75 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The abdomen was soft, with normal bowel sounds and mild tenderness of the upper abdomen and with no distention, masses, or hepatosplenomegaly. There was no pedal or pretibial edema, and the remainder of the examination was unchanged. Laboratory test results are shown in Table 1. An electrocardiogram was normal. After the intravenous administration of 1 liter of normal saline, the patient voided only 2 ml of urine. Urinalysis revealed turbid, amber urine, with 2+ blood, 3+ albumin, 3+ leukocyte esterase, a specific gravity of 1.012, and a pH of 5.0 by dipstick; microscopic examination of the sediment revealed transitional cells, squamous cells, amorphous crystals, mucin, bacteria, and white-cell clumps, as well as 20 to 50 red cells per high-power field and more than 100 white cells per high-power field. A urine pregnancy test was negative. Ultrasonography of the bladder, performed at the bedside, revealed that the bladder was collapsed. Ondansetron was administered intravenously.

The patient was admitted to the hospital, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 15-year-old girl was admitted to this hospital during the summer because of acute kidney injury.

The patient had been well until 8 days before admission, when painful cramping in the lower abdomen and bloody diarrhea developed. Bowel movements occurred approximately every hour, and the patient was unable to sleep. She took ibuprofen but had no relief of the abdominal pain.

On the third day of illness, two episodes of nonbloody, nonbilious emesis occurred. The following day, the patient was seen by her primary care pediatrician. She reported that she felt fatigued and that the diarrhea, abdominal cramping, and vomiting had persisted; she had not had a fever. The results of a physical examination were normal. Stool samples were obtained for cultures for salmonella, shigella, campylobacter, aeromonas, plesiomonas, and Escherichia coli O157:H7, and antigen-detection tests were performed for rotavirus, giardia, and Clostridium difficile toxin. The patient was advised to stop taking ibuprofen, to take loperamide and acetaminophen as needed, and to drink an electrolyte-containing oral rehydration solution. During the next 3 days, the diarrhea resolved, but the patient continued to vomit several times each day and the abdominal cramping became localized to the epigastrium. The stool cultures and antigen-detection tests were negative. Her mother called the pediatrician’s office on the seventh day of illness, and ondansetron was prescribed.

The following morning, the patient returned to the pediatrician’s office because of persistent painful cramping in the epigastrium. On examination, she appeared mildly ill and slightly pale. The temperature was 36.5°C, and the pulse 98 beats per minute. The abdomen was soft, with normal bowel sounds and mild, diffuse tenderness and with no distention, masses, or guarding. The remainder of the examination was normal. Ranitidine and a probiotic were recommended. Two hours after this appointment, the patient’s mother called the office to report that the patient had vomited again; she was advised to take the patient to the emergency department at a local hospital for further evaluation and treatment.

Table 1.

Laboratory Data.
In the emergency department at the other hospital, the patient reported that the volume of urine output had decreased. On examination, she appeared slightly pale. The temperature was 36.9°C, the pulse 80 beats per minute, the blood pressure 111/69 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The remainder of the examination was unchanged. Laboratory test results are shown in Table 1. Imaging studies of the abdomen were performed.

Figure 1.

Abdominal Ultrasound Images.
Dr. Pallavi Sagar: An abdominal radiograph was normal. Abdominal ultrasonography revealed a large amount of layering sludge in the gallbladder, with no thickening of the gallbladder wall (Figure 1A). Both kidneys were normal in size (length of the right kidney, 11.5 cm; length of the left kidney, 10.6 cm), with mildly echogenic renal parenchyma (Figure 1B and 1C). The urinary tract was not dilated, and the bladder was partially distended. A moderate amount of ascites was present in the lower abdomen, and a trace amount was present in Morison’s pouch (Figure 1D).

Dr. Healy: Two liters of normal saline were administered intravenously; afterward, the patient did not have any urine output. After consultation with a pediatric nephrologist, the patient was transferred to the emergency department at this hospital.

On arrival, the patient rated her abdominal pain at 3 on a scale of 0 to 10, with 10 indicating the most severe pain. She reported that, during the past week, her weight had decreased by 3 kg and then increased by 1 kg. She had a history of attention deficit–hyperactivity disorder, anxiety, and labial adhesions. During the previous 7 months, she had been seen by her pediatrician on three occasions because of intermittent dysuria; tests for urinary tract infection, chlamydia, and gonorrhea had been negative. Medications included citalopram and methylphenidate; she had an allergy to azithromycin, which had caused a rash. The patient lived with her parents and siblings in New England. Just before the onset of the current illness, she had spent several days in New York City, where she had eaten food purchased from street vendors. She had had no known exposure to sick persons, was not sexually active, and did not smoke cigarettes, drink alcohol, or use illicit drugs. Her maternal grandfather had the antiphospholipid syndrome, her paternal grandmother had hypothyroidism, and her mother had had gestational hypertension; there was no known family history of kidney disease or inflammatory bowel disease.

On examination, the patient appeared tired but otherwise well. The temperature was 36.9°C, the pulse 71 beats per minute, the blood pressure 124/75 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The abdomen was soft, with normal bowel sounds and mild tenderness of the upper abdomen and with no distention, masses, or hepatosplenomegaly. There was no pedal or pretibial edema, and the remainder of the examination was unchanged. Laboratory test results are shown in Table 1. An electrocardiogram was normal. After the intravenous administration of 1 liter of normal saline, the patient voided only 2 ml of urine. Urinalysis revealed turbid, amber urine, with 2+ blood, 3+ albumin, 3+ leukocyte esterase, a specific gravity of 1.012, and a pH of 5.0 by dipstick; microscopic examination of the sediment revealed transitional cells, squamous cells, amorphous crystals, mucin, bacteria, and white-cell clumps, as well as 20 to 50 red cells per high-power field and more than 100 white cells per high-power field. A urine pregnancy test was negative. Ultrasonography of the bladder, performed at the bedside, revealed that the bladder was collapsed. Ondansetron was administered intravenously.

The patient was admitted to the hospital, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""This is a 15-year-old girl who presents with acute kidney injury, abdominal cramping, bloody diarrhea, vomiting, and decreased urine output. The differential diagnosis for this patient includes hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), acute glomerulonephritis, and acute interstitial nephritis. The patient's history of bloody diarrhea and vomiting prior to the onset of kidney injury is suggestive of HUS, which is often preceded by a gastrointestinal infection. The negative stool cultures and antigen-detection tests make an infectious cause less likely, but they do not rule out infection with Shiga toxin-producing E. coli, which is a common cause of HUS. The patient's abdominal pain, vomiting, and decreased urine output could also be explained by acute glomerulonephritis or acute interstitial nephritis, but these conditions would not typically cause bloody diarrhea. TTP could cause kidney injury and abdominal pain, but it would also typically cause neurological symptoms, which this patient does not have. The patient's lab results show anemia, thrombocytopenia, and elevated creatinine, which are consistent with HUS. The presence of sludge in the gallbladder on ultrasound could be a result of dehydration, which could also contribute to kidney injury. \n\nDiagnosis: Hemolytic Uremic Syndrome (HUS) is the most likely diagnosis.""
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}",Hemolytic Uremic Syndrome (HUS),Y
10.1056/NEJMcpc1802825,"Case 18-2018: A 45-Year-Old Woman with Hypertension, Fatigue, and Altered Mental Status",,"Cushing’s syndrome due to a well-differentiated, low-grade thymic neuroendocrine tumor with corticotropin secretion.",Cushing’s syndrome due to ectopic corticotropin secretion.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 45-year-old woman was admitted to this hospital because of dyspnea on exertion, fatigue, and confusion.

The patient had been in her usual state of health until 18 months before the current admission, when the blood pressure was noted to be 140/90 mm Hg during a routine appointment with her primary care physician. Therapy with oral contraceptive pills was discontinued, but the blood pressure was persistently elevated when it was measured at home and during subsequent clinical evaluations. Results of duplex ultrasonography of the bilateral renal arterial vasculature were normal, as were levels of thyrotropin, plasma free catecholamines, plasma metanephrines, and aldosterone. Transthoracic echocardiography revealed normal ventricular function, with no evidence of valvular disease or left ventricular hypertrophy; the interventricular septal wall thickness was 11 mm (normal range, 7 to 11). Lisinopril was administered, and the blood pressure decreased to 120/80 mm Hg.

Table 1.

Laboratory Data.
Four weeks before the current admission, swelling of the legs, abdominal distention, intermittent dyspnea on exertion, and fatigue developed, and the patient was evaluated in the emergency department of this hospital. She reported a weight gain of 4.5 kg during the previous month, occasional episodes of confusion, and two episodes of burning chest pain during exercise that had lasted for 2 minutes each and were relieved with rest. On examination, the temperature was 36.8°C, the blood pressure 180/110 mm Hg, the heart rate 73 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 66.9 kg; approximately 5 months earlier, at a clinic visit, it had been 67.1 kg. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 22. A systolic murmur (grade 2/6) was best heard at the left sternal border. The jugular venous pressure was estimated to be 10 cm of water. The abdomen was soft, nontender, and slightly distended. There was trace nonpitting edema in the legs. The remainder of the physical examination was normal. An electrocardiogram showed a normal sinus rhythm and left-axis deviation. Laboratory test results are shown in Table 1. A chest radiograph showed a normal cardiac silhouette and small bilateral pleural effusions, with no opacities or pulmonary edema. The patient was admitted to this hospital.

The patient had a history of endometriosis and dysmenorrhea, conditions that had been treated with a levonorgestrel-releasing intrauterine system. She had a remote history of palpitations that were not associated with evidence of arrhythmia on Holter monitoring. The only medication was lisinopril. The patient’s mother and sister had both had venous thromboses and miscarriages. Her maternal uncle had hypertrophic cardiomyopathy; there was no family history of sudden cardiac death. The patient did not drink alcohol, smoke tobacco, or use illicit drugs. She was married and worked as a lawyer.

Furosemide was administered intravenously, and the patient reported a decrease in the dyspnea and swelling. Daily therapy with a low dose of oral furosemide was initiated. A transthoracic echocardiogram showed hyperdynamic left ventricular systolic function, with an ejection fraction of 76% (normal range, 50 to 75), as well as biventricular hypertrophy, an interventricular septal wall thickness of 14 mm, mild mitral regurgitation, systolic anterior motion of the mitral-valve leaflets, and accelerated flow in the left ventricular outflow tract. Because the blood pressure was persistently elevated, the dose of lisinopril was increased and treatment with metoprolol and nifedipine was initiated. On the third hospital day, the patient was discharged home.

Three weeks before the current admission, dyspnea on exertion and fatigue recurred, and the patient was again evaluated in the emergency department of this hospital. She reported a 3-day history of malaise and night sweats. On examination, the temperature was 36.8°C, the blood pressure 148/96 mm Hg, the heart rate 84 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while she was breathing ambient air. The weight was 65.3 kg. Jugular venous pulsation was not visible, and there was no leg edema; otherwise, the results of the physical examination had not changed from the previous week. Laboratory test results are shown in Table 1. Blood and urine cultures were sterile. Tests for human immunodeficiency virus (HIV) type 1 p24 antigen and HIV type 1 and type 2 antibodies were negative. An interferon-_ release assay for tuberculosis was nonreactive. A chest radiograph showed that the pleural effusions had resolved and that no opacities or pulmonary edema had developed. The patient was admitted to this hospital, and additional cardiac imaging studies were obtained.

Figure 1.

MRI and CT Angiogram of the Chest.
Dr. Michael T. Lu: Magnetic resonance imaging (MRI) of the chest, performed before and after the administration of gadolinium, revealed asymmetric left ventricular septal hypertrophy (maximal wall thickness, 21 mm) and mild left ventricular enlargement with hyperdynamic systolic function (ejection fraction, 71%). There was no evidence of myocardial iron overload, and there were small areas of late gadolinium enhancement in the midwall. These findings were compatible with fibrosis due to hypertrophic cardiomyopathy (Figure 1A and 1B).

Dr. Ingham: The patient’s prescribed dose of oral furosemide was administered, but orthostatic hypotension developed. She received intravenous fluids, and furosemide therapy was discontinued. She did not have a fever during the hospitalization. The white-cell count decreased but did not normalize. On the sixth hospital day, the patient was discharged home. The weight was 62.1 kg.

At home, the fatigue continued to decrease until 2 weeks after discharge, when recurrent fatigue, fevers, and palpitations developed. The patient was again evaluated in the emergency department of this hospital. The patient’s husband reported that she had become increasingly confused, irritable, and anxious. He also noted that she appeared to be weak globally, with increased respiratory effort on exertion. The patient reported frequent urination and increased thirst.

On examination, the temperature was 36.2°C, the blood pressure 135/80 mm Hg, the heart rate 98 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 60.0 kg. The patient was awake, alert, and cooperative, but she was unable to state the year or to count backward from 100 in increments of 7. She occasionally responded to questions inappropriately and with confabulation. Cranial-nerve function was normal, although the first cranial nerve was not tested. Strength was 4/5 in the proximal muscles of the arms and legs. Sensation was normal. A systolic murmur (grade 3/6) was best heard at the left sternal border. Jugular venous pulsation was not visible, and there was no leg edema. The amount of scalp hair had decreased, and hair growth on the upper lip and chin had increased. She had no rashes, bruises, striae, or hyperpigmentation. The remainder of the physical examination was normal. Laboratory test results are shown in Table 1. Additional imaging studies were obtained.

Dr. Lu: Computed tomographic (CT) angiography of the chest, performed after the administration of intravenous contrast material, revealed segmental and subsegmental pulmonary emboli in the right lower lobe, with no evidence of strain on the right side of the heart or of pulmonary infarction. There was diffuse thickening of both adrenal glands (Figure 1C and 1D). MRI, angiography, and venography of the head revealed no evidence of a mass, acute infarction, arterial abnormalities, or venous sinus thrombosis.

Dr. Ingham: The patient was admitted to this hospital. A continuous infusion of heparin was administered intravenously, and her prescribed medications were continued. Despite having a normal diet, the patient had persistent hypokalemia and received aggressive potassium supplementation.

A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 45-year-old woman was admitted to this hospital because of dyspnea on exertion, fatigue, and confusion.

The patient had been in her usual state of health until 18 months before the current admission, when the blood pressure was noted to be 140/90 mm Hg during a routine appointment with her primary care physician. Therapy with oral contraceptive pills was discontinued, but the blood pressure was persistently elevated when it was measured at home and during subsequent clinical evaluations. Results of duplex ultrasonography of the bilateral renal arterial vasculature were normal, as were levels of thyrotropin, plasma free catecholamines, plasma metanephrines, and aldosterone. Transthoracic echocardiography revealed normal ventricular function, with no evidence of valvular disease or left ventricular hypertrophy; the interventricular septal wall thickness was 11 mm (normal range, 7 to 11). Lisinopril was administered, and the blood pressure decreased to 120/80 mm Hg.

Table 1.

Laboratory Data.
Four weeks before the current admission, swelling of the legs, abdominal distention, intermittent dyspnea on exertion, and fatigue developed, and the patient was evaluated in the emergency department of this hospital. She reported a weight gain of 4.5 kg during the previous month, occasional episodes of confusion, and two episodes of burning chest pain during exercise that had lasted for 2 minutes each and were relieved with rest. On examination, the temperature was 36.8°C, the blood pressure 180/110 mm Hg, the heart rate 73 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 66.9 kg; approximately 5 months earlier, at a clinic visit, it had been 67.1 kg. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 22. A systolic murmur (grade 2/6) was best heard at the left sternal border. The jugular venous pressure was estimated to be 10 cm of water. The abdomen was soft, nontender, and slightly distended. There was trace nonpitting edema in the legs. The remainder of the physical examination was normal. An electrocardiogram showed a normal sinus rhythm and left-axis deviation. Laboratory test results are shown in Table 1. A chest radiograph showed a normal cardiac silhouette and small bilateral pleural effusions, with no opacities or pulmonary edema. The patient was admitted to this hospital.

The patient had a history of endometriosis and dysmenorrhea, conditions that had been treated with a levonorgestrel-releasing intrauterine system. She had a remote history of palpitations that were not associated with evidence of arrhythmia on Holter monitoring. The only medication was lisinopril. The patient’s mother and sister had both had venous thromboses and miscarriages. Her maternal uncle had hypertrophic cardiomyopathy; there was no family history of sudden cardiac death. The patient did not drink alcohol, smoke tobacco, or use illicit drugs. She was married and worked as a lawyer.

Furosemide was administered intravenously, and the patient reported a decrease in the dyspnea and swelling. Daily therapy with a low dose of oral furosemide was initiated. A transthoracic echocardiogram showed hyperdynamic left ventricular systolic function, with an ejection fraction of 76% (normal range, 50 to 75), as well as biventricular hypertrophy, an interventricular septal wall thickness of 14 mm, mild mitral regurgitation, systolic anterior motion of the mitral-valve leaflets, and accelerated flow in the left ventricular outflow tract. Because the blood pressure was persistently elevated, the dose of lisinopril was increased and treatment with metoprolol and nifedipine was initiated. On the third hospital day, the patient was discharged home.

Three weeks before the current admission, dyspnea on exertion and fatigue recurred, and the patient was again evaluated in the emergency department of this hospital. She reported a 3-day history of malaise and night sweats. On examination, the temperature was 36.8°C, the blood pressure 148/96 mm Hg, the heart rate 84 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while she was breathing ambient air. The weight was 65.3 kg. Jugular venous pulsation was not visible, and there was no leg edema; otherwise, the results of the physical examination had not changed from the previous week. Laboratory test results are shown in Table 1. Blood and urine cultures were sterile. Tests for human immunodeficiency virus (HIV) type 1 p24 antigen and HIV type 1 and type 2 antibodies were negative. An interferon-_ release assay for tuberculosis was nonreactive. A chest radiograph showed that the pleural effusions had resolved and that no opacities or pulmonary edema had developed. The patient was admitted to this hospital, and additional cardiac imaging studies were obtained.

Figure 1.

MRI and CT Angiogram of the Chest.
Dr. Michael T. Lu: Magnetic resonance imaging (MRI) of the chest, performed before and after the administration of gadolinium, revealed asymmetric left ventricular septal hypertrophy (maximal wall thickness, 21 mm) and mild left ventricular enlargement with hyperdynamic systolic function (ejection fraction, 71%). There was no evidence of myocardial iron overload, and there were small areas of late gadolinium enhancement in the midwall. These findings were compatible with fibrosis due to hypertrophic cardiomyopathy (Figure 1A and 1B).

Dr. Ingham: The patient’s prescribed dose of oral furosemide was administered, but orthostatic hypotension developed. She received intravenous fluids, and furosemide therapy was discontinued. She did not have a fever during the hospitalization. The white-cell count decreased but did not normalize. On the sixth hospital day, the patient was discharged home. The weight was 62.1 kg.

At home, the fatigue continued to decrease until 2 weeks after discharge, when recurrent fatigue, fevers, and palpitations developed. The patient was again evaluated in the emergency department of this hospital. The patient’s husband reported that she had become increasingly confused, irritable, and anxious. He also noted that she appeared to be weak globally, with increased respiratory effort on exertion. The patient reported frequent urination and increased thirst.

On examination, the temperature was 36.2°C, the blood pressure 135/80 mm Hg, the heart rate 98 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The weight was 60.0 kg. The patient was awake, alert, and cooperative, but she was unable to state the year or to count backward from 100 in increments of 7. She occasionally responded to questions inappropriately and with confabulation. Cranial-nerve function was normal, although the first cranial nerve was not tested. Strength was 4/5 in the proximal muscles of the arms and legs. Sensation was normal. A systolic murmur (grade 3/6) was best heard at the left sternal border. Jugular venous pulsation was not visible, and there was no leg edema. The amount of scalp hair had decreased, and hair growth on the upper lip and chin had increased. She had no rashes, bruises, striae, or hyperpigmentation. The remainder of the physical examination was normal. Laboratory test results are shown in Table 1. Additional imaging studies were obtained.

Dr. Lu: Computed tomographic (CT) angiography of the chest, performed after the administration of intravenous contrast material, revealed segmental and subsegmental pulmonary emboli in the right lower lobe, with no evidence of strain on the right side of the heart or of pulmonary infarction. There was diffuse thickening of both adrenal glands (Figure 1C and 1D). MRI, angiography, and venography of the head revealed no evidence of a mass, acute infarction, arterial abnormalities, or venous sinus thrombosis.

Dr. Ingham: The patient was admitted to this hospital. A continuous infusion of heparin was administered intravenously, and her prescribed medications were continued. Despite having a normal diet, the patient had persistent hypokalemia and received aggressive potassium supplementation.

A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 45-year-old woman presenting with dyspnea on exertion, fatigue, and confusion. She has a history of hypertension, endometriosis, and dysmenorrhea. She also has a family history of venous thromboses, miscarriages, and hypertrophic cardiomyopathy. Her symptoms have been ongoing for 18 months, with recent worsening including leg swelling, abdominal distention, weight gain, and episodes of confusion and chest pain. She has been found to have biventricular hypertrophy, systolic anterior motion of the mitral-valve leaflets, and accelerated flow in the left ventricular outflow tract on echocardiogram. Her blood pressure has been persistently elevated despite medication. \n\nThe differential diagnosis for this patient includes hypertrophic cardiomyopathy, pheochromocytoma, Cushing's syndrome, and hyperaldosteronism. The patient's family history of hypertrophic cardiomyopathy and her echocardiogram findings make this a strong possibility. However, her persistent hypertension despite medication, hypokalemia, and recent weight gain also suggest a possible endocrine cause. Pheochromocytoma could cause hypertension and tachycardia, but this is less likely given the patient's normal plasma free catecholamines and metanephrines. Hyperaldosteronism could cause hypertension and hypokalemia, but the patient's normal aldosterone level makes this less likely. Cushing's syndrome could cause hypertension, weight gain, and hypokalemia, and could also explain the patient's recent confusion and increased hair growth. \n\nGiven the patient's symptoms and lab findings, the most likely diagnosis is Cushing's syndrome. This is supported by the patient's persistent hypertension, hypokalemia, weight gain, confusion, and increased hair growth. The diffuse thickening of both adrenal glands seen on CT angiography also supports this diagnosis. \n\nDiagnosis: Cushing's syndrome.""
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10.1056/NEJMcpc1712228,Case 17-2018: A 40-Year-Old Woman with Leg Swelling and Abdominal Distention and Pain,,"Membranous nephropathy, PLA2R type.","Primary membranous nephropathy, complicated by thromboembolic disease.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 40-year-old woman was evaluated at this hospital because of progressive edema of the legs, as well as abdominal distention and pain.

The patient had been in good health until approximately 10 months before this evaluation, when episodes of pain and swelling developed in the feet and ankles. Initially, the episodes occurred during the evening, after prolonged standing during the day. During subsequent months, the episodes became more frequent and began to occur earlier in the day. The swelling progressed to involve the lower legs and thighs. The patient was evaluated by her primary care physician, and compression stockings were recommended.

Five months before this evaluation, pain developed in the back and flank on the left side, and the patient was evaluated in the emergency department of another hospital. A provisional diagnosis of musculoskeletal pain was made, and benzodiazepines and muscle relaxants were prescribed.

Despite the administration of these medications, the back and flank pain persisted, and the patient was evaluated in the emergency department of a second hospital. The weight was 82 kg. The platelet count, results of kidney-function tests, and blood levels of hemoglobin, electrolytes, and glucose were normal. Tests were negative for hepatitis C virus antibody and for hepatitis B virus surface antigen and surface antibody. The blood albumin level was 1.9 g per deciliter (reference range, 4.0 to 5.0), and the white-cell count was 12,500 per cubic millimeter (reference range, 4500 to 11,000), with a normal differential count. The d-dimer level was more than 20 _g per milliliter (reference range, 0.27 to 20). An imaging study of the chest was scheduled, and nitrofurantoin was prescribed for a suspected urinary tract infection.

Dr. Midhir J. Patel: The next day, computed tomographic (CT) angiography of the chest revealed findings consistent with a calcified granuloma (measuring 3 mm in diameter) in the right upper lobe and multiple pulmonary emboli involving the main, lobar, segmental, and subsegmental pulmonary arteries bilaterally.

Dr. Wolf: Anticoagulation with low-molecular-weight heparin was administered, and the patient was admitted to the second hospital. Over a period of 3 days, the anticoagulation regimen was transitioned to apixaban, and the back and flank pain diminished. The patient was discharged home with prescriptions for apixaban and nitrofurantoin. The pulmonary emboli were considered to be unprovoked, and evaluation by a hematologist was recommended.

While the patient was receiving anticoagulation, she had persistent leg swelling, but the back and flank pain did not recur. Evaluation by a hematologist did not reveal an underlying cause of the pulmonary embolism, and anticoagulation of indefinite duration was advised.

Four weeks before this evaluation, the swelling of the legs worsened and abdominal distention developed. Intermittent swelling of the hands occurred, as did swelling around the eyes in the morning upon awakening. The patient had a consultation with a vascular specialist, but no primary venous disease of the legs was identified.

The abdominal distention worsened, and 1 week before this evaluation, diffuse, crampy abdominal pain with nausea developed. The abdominal pain waxed and waned for several days but worsened on the day of this evaluation. The patient also had dyspnea, and she presented to the emergency department of the second hospital, where additional imaging studies were obtained.

Figure 1.

CT Scan of the Abdomen and Pelvis.
Dr. Patel: CT of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed a nonocclusive thrombus in the right renal vein. Wall thickening of the gastric antrum and proximal small bowel, multiple enlarged mesenteric lymph nodes, mild mesenteric edema, and evidence of small-volume ascites were also noted (Figure 1).

Dr. Wolf: On the basis of the results of these imaging studies, the patient sought evaluation in the emergency department of this hospital. She reported ongoing abdominal pain, nausea, and loose stools. She noted an unintentional weight gain of 10 kg since the leg swelling had begun 10 months previously, despite no change in appetite or food intake. She also reported increases in urinary frequency and sensation of thirst. She had no chest pain, hematuria, hemoptysis, dark stools, night sweats, fatigue, joint symptoms, or eye or ear symptoms.

The patient, who was black, had a medical history that was notable for hypothyroidism, latent tuberculosis with a previous negative chest radiograph, two spontaneous vaginal deliveries, and ectopic pregnancy. She had undergone an ovary-sparing abdominal hysterectomy for fibroid uterus and an appendectomy. Medications included levothyroxine and apixaban. There had been no adverse reactions to medications. She did not use nonsteroidal antiinflammatory drugs. The patient had grown up on a Caribbean island and had immigrated to the United States when she was 19 years of age. She worked as an assistant in a health care facility and lived with her husband and two healthy children. There was no history of alcohol, tobacco, or illicit-drug use. There was no family history of renal, thromboembolic, or autoimmune disease.

On examination, the temperature was 36.8°C, the pulse 76 beats per minute, the blood pressure 131/70 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 88.5 kg, the height 173 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 29.7. There was 2+ edema of the lower and upper legs. The jugular venous pressure was 8 cm of water. There was no periorbital or hand edema. The abdomen was distended and mildly, diffusely tender, with well-healed surgical scars. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Blood levels of globulin, phosphorus, magnesium, lipase, lactic acid, bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were normal, as were the prothrombin time and partial-thromboplastin time. Urinalysis was negative for glucose, bilirubin, ketones, nitrite, and leukocyte esterase. Tests were negative for anti–double-stranded DNA, rheumatoid factor antibody, human immunodeficiency virus (HIV) antibody, antitreponemal antibody, and hepatitis C virus antibody, as well as for hepatitis B virus surface antibody, surface antigen, and core antibody. The serum protein electrophoresis pattern was normal, except for a diffuse decrease in gamma globulin. Other laboratory test results are shown in Table 1. An electrocardiogram was normal, and ultrasonography of the kidneys revealed normal kidney size and echotexture.

Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 40-year-old woman was evaluated at this hospital because of progressive edema of the legs, as well as abdominal distention and pain.

The patient had been in good health until approximately 10 months before this evaluation, when episodes of pain and swelling developed in the feet and ankles. Initially, the episodes occurred during the evening, after prolonged standing during the day. During subsequent months, the episodes became more frequent and began to occur earlier in the day. The swelling progressed to involve the lower legs and thighs. The patient was evaluated by her primary care physician, and compression stockings were recommended.

Five months before this evaluation, pain developed in the back and flank on the left side, and the patient was evaluated in the emergency department of another hospital. A provisional diagnosis of musculoskeletal pain was made, and benzodiazepines and muscle relaxants were prescribed.

Despite the administration of these medications, the back and flank pain persisted, and the patient was evaluated in the emergency department of a second hospital. The weight was 82 kg. The platelet count, results of kidney-function tests, and blood levels of hemoglobin, electrolytes, and glucose were normal. Tests were negative for hepatitis C virus antibody and for hepatitis B virus surface antigen and surface antibody. The blood albumin level was 1.9 g per deciliter (reference range, 4.0 to 5.0), and the white-cell count was 12,500 per cubic millimeter (reference range, 4500 to 11,000), with a normal differential count. The d-dimer level was more than 20 _g per milliliter (reference range, 0.27 to 20). An imaging study of the chest was scheduled, and nitrofurantoin was prescribed for a suspected urinary tract infection.

Dr. Midhir J. Patel: The next day, computed tomographic (CT) angiography of the chest revealed findings consistent with a calcified granuloma (measuring 3 mm in diameter) in the right upper lobe and multiple pulmonary emboli involving the main, lobar, segmental, and subsegmental pulmonary arteries bilaterally.

Dr. Wolf: Anticoagulation with low-molecular-weight heparin was administered, and the patient was admitted to the second hospital. Over a period of 3 days, the anticoagulation regimen was transitioned to apixaban, and the back and flank pain diminished. The patient was discharged home with prescriptions for apixaban and nitrofurantoin. The pulmonary emboli were considered to be unprovoked, and evaluation by a hematologist was recommended.

While the patient was receiving anticoagulation, she had persistent leg swelling, but the back and flank pain did not recur. Evaluation by a hematologist did not reveal an underlying cause of the pulmonary embolism, and anticoagulation of indefinite duration was advised.

Four weeks before this evaluation, the swelling of the legs worsened and abdominal distention developed. Intermittent swelling of the hands occurred, as did swelling around the eyes in the morning upon awakening. The patient had a consultation with a vascular specialist, but no primary venous disease of the legs was identified.

The abdominal distention worsened, and 1 week before this evaluation, diffuse, crampy abdominal pain with nausea developed. The abdominal pain waxed and waned for several days but worsened on the day of this evaluation. The patient also had dyspnea, and she presented to the emergency department of the second hospital, where additional imaging studies were obtained.

Figure 1.

CT Scan of the Abdomen and Pelvis.
Dr. Patel: CT of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed a nonocclusive thrombus in the right renal vein. Wall thickening of the gastric antrum and proximal small bowel, multiple enlarged mesenteric lymph nodes, mild mesenteric edema, and evidence of small-volume ascites were also noted (Figure 1).

Dr. Wolf: On the basis of the results of these imaging studies, the patient sought evaluation in the emergency department of this hospital. She reported ongoing abdominal pain, nausea, and loose stools. She noted an unintentional weight gain of 10 kg since the leg swelling had begun 10 months previously, despite no change in appetite or food intake. She also reported increases in urinary frequency and sensation of thirst. She had no chest pain, hematuria, hemoptysis, dark stools, night sweats, fatigue, joint symptoms, or eye or ear symptoms.

The patient, who was black, had a medical history that was notable for hypothyroidism, latent tuberculosis with a previous negative chest radiograph, two spontaneous vaginal deliveries, and ectopic pregnancy. She had undergone an ovary-sparing abdominal hysterectomy for fibroid uterus and an appendectomy. Medications included levothyroxine and apixaban. There had been no adverse reactions to medications. She did not use nonsteroidal antiinflammatory drugs. The patient had grown up on a Caribbean island and had immigrated to the United States when she was 19 years of age. She worked as an assistant in a health care facility and lived with her husband and two healthy children. There was no history of alcohol, tobacco, or illicit-drug use. There was no family history of renal, thromboembolic, or autoimmune disease.

On examination, the temperature was 36.8°C, the pulse 76 beats per minute, the blood pressure 131/70 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The weight was 88.5 kg, the height 173 cm, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 29.7. There was 2+ edema of the lower and upper legs. The jugular venous pressure was 8 cm of water. There was no periorbital or hand edema. The abdomen was distended and mildly, diffusely tender, with well-healed surgical scars. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Blood levels of globulin, phosphorus, magnesium, lipase, lactic acid, bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were normal, as were the prothrombin time and partial-thromboplastin time. Urinalysis was negative for glucose, bilirubin, ketones, nitrite, and leukocyte esterase. Tests were negative for anti–double-stranded DNA, rheumatoid factor antibody, human immunodeficiency virus (HIV) antibody, antitreponemal antibody, and hepatitis C virus antibody, as well as for hepatitis B virus surface antibody, surface antigen, and core antibody. The serum protein electrophoresis pattern was normal, except for a diffuse decrease in gamma globulin. Other laboratory test results are shown in Table 1. An electrocardiogram was normal, and ultrasonography of the kidneys revealed normal kidney size and echotexture.

Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 40-year-old woman presenting with progressive edema of the legs, abdominal distention and pain, and a history of pulmonary emboli. The differential diagnosis for this patient includes nephrotic syndrome, liver disease, congestive heart failure, and malignancy. The patient's lab results show a low albumin level, which is consistent with nephrotic syndrome, liver disease, and malnutrition. However, the patient does not have any signs of liver disease such as jaundice or ascites, and her liver function tests are normal. She also does not have any signs of congestive heart failure such as shortness of breath or jugular venous distention. The patient's weight gain despite no change in appetite or food intake, along with her edema, suggests that she is retaining fluid, which is consistent with nephrotic syndrome. The patient's history of thromboembolic events is also consistent with nephrotic syndrome, as this condition can increase the risk of blood clots. The patient's urinalysis is negative for protein, which is unusual for nephrotic syndrome, but it is possible that her proteinuria is intermittent or that it was missed on this test. The patient's renal ultrasound is normal, which makes a renal malignancy less likely. \n\nDiagnosis: Nephrotic Syndrome.""
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10.1056/NEJMcpc1712227,"Case 16-2018: A 45-Year-Old Man with Fever, Thrombocytopenia, and Elevated Aminotransferase Levels",,Anaplasma phagocytophilum infection,"Tickborne disease, most likely anaplasmosis.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 45-year-old man presented to the emergency department of this hospital during the summer with fever, thrombocytopenia, and elevated aminotransferase levels.

Three weeks before presentation, fever occurred (with temperatures as high as 40.0°C), along with fatigue and malaise. The patient took acetaminophen and diphenhydramine to alleviate the symptoms. After approximately 5 days, the fever and fatigue had subsided but an erythematous, maculopapular rash had developed on the scalp. The rash lasted for 3 days and then spontaneously resolved.

Three days before presentation, fever recurred, along with chills and malaise. Despite the administration of acetaminophen, the fever persisted. After 2 days, the patient sought medical attention at an urgent care clinic. His temperature was 40.0°C, and laboratory test results were notable for a platelet count of 45,000 per cubic millimeter (reference range, 140,000 to 400,000). He was instructed to return the next day. When he returned, his temperature was 38.9°C, the platelet count was 21,000 per cubic millimeter, and the serum sodium level was 124 mmol per liter (reference range, 135 to 146). Ibuprofen was administered orally, and he was referred to the emergency department of this hospital and was admitted for evaluation.

In the emergency department, a review of systems was notable for the presence of anorexia during the previous 3 weeks and the occurrence of loose, nonbloody stools for 3 days. The patient had no weight loss, bleeding, or other gastrointestinal, pulmonary, neurologic, joint, or genitourinary symptoms; he reported no contacts with sick persons. He had no notable events in his medical history, except for an evaluation for mild bilateral gynecomastia 5 years earlier. He took no medications and had no known allergies. He worked as a manager of a craft shop. He lived in a wooded area in Massachusetts with his wife and two healthy daughters, and he ran once or twice weekly in a marshy area near his home. He had a house cat that was permitted to go outdoors. There was no history of use of tobacco or illicit substances; he consumed two alcoholic beverages weekly. He traveled to Mexico annually during the winter. His mother had had atrial fibrillation and heart failure, and his father had had lung cancer. He had one brother and one sister, and they were both healthy.

On examination, the temperature was 36.7°C, the blood pressure 117/60 mm Hg, the pulse 113 beats per minute, and the oxygen saturation 97% while the patient was breathing ambient air. Six hours later, the temperature was 39.3°C. The patient was described as appearing well. There was a faint erythematous, macular rash on the chest. Conjunctival erythema was present, with no icterus. There was no cervical, supraclavicular, axillary, or inguinal lymphadenopathy. Cardiac examination revealed a tachycardic rhythm, with no murmur. Neurologic examination was normal. A circular skin lesion (measuring 1 cm in diameter) with a central scab was noted below the left lateral malleolus.

Table 1.

Laboratory Data.
A chest radiograph was normal. An electrocardiogram showed sinus tachycardia and was otherwise normal. Levels of calcium, magnesium, lactate, total protein, globulin, amylase, and lipase were normal, as were the prothrombin time, partial-thromboplastin time, and white-cell differential count. Tests for hepatitis A virus antibody and hepatitis B virus surface antibody were positive. Screening blood tests for human immunodeficiency virus (HIV) antibody, hepatitis C virus antibody, and hepatitis B virus IgM antibody and surface antigen were negative. Other laboratory test results are shown in Table 1. Samples of the blood and urine were obtained for culture, and normal saline was administered intravenously.

Diagnostic tests were performed.

Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 45-year-old man presented to the emergency department of this hospital during the summer with fever, thrombocytopenia, and elevated aminotransferase levels.

Three weeks before presentation, fever occurred (with temperatures as high as 40.0°C), along with fatigue and malaise. The patient took acetaminophen and diphenhydramine to alleviate the symptoms. After approximately 5 days, the fever and fatigue had subsided but an erythematous, maculopapular rash had developed on the scalp. The rash lasted for 3 days and then spontaneously resolved.

Three days before presentation, fever recurred, along with chills and malaise. Despite the administration of acetaminophen, the fever persisted. After 2 days, the patient sought medical attention at an urgent care clinic. His temperature was 40.0°C, and laboratory test results were notable for a platelet count of 45,000 per cubic millimeter (reference range, 140,000 to 400,000). He was instructed to return the next day. When he returned, his temperature was 38.9°C, the platelet count was 21,000 per cubic millimeter, and the serum sodium level was 124 mmol per liter (reference range, 135 to 146). Ibuprofen was administered orally, and he was referred to the emergency department of this hospital and was admitted for evaluation.

In the emergency department, a review of systems was notable for the presence of anorexia during the previous 3 weeks and the occurrence of loose, nonbloody stools for 3 days. The patient had no weight loss, bleeding, or other gastrointestinal, pulmonary, neurologic, joint, or genitourinary symptoms; he reported no contacts with sick persons. He had no notable events in his medical history, except for an evaluation for mild bilateral gynecomastia 5 years earlier. He took no medications and had no known allergies. He worked as a manager of a craft shop. He lived in a wooded area in Massachusetts with his wife and two healthy daughters, and he ran once or twice weekly in a marshy area near his home. He had a house cat that was permitted to go outdoors. There was no history of use of tobacco or illicit substances; he consumed two alcoholic beverages weekly. He traveled to Mexico annually during the winter. His mother had had atrial fibrillation and heart failure, and his father had had lung cancer. He had one brother and one sister, and they were both healthy.

On examination, the temperature was 36.7°C, the blood pressure 117/60 mm Hg, the pulse 113 beats per minute, and the oxygen saturation 97% while the patient was breathing ambient air. Six hours later, the temperature was 39.3°C. The patient was described as appearing well. There was a faint erythematous, macular rash on the chest. Conjunctival erythema was present, with no icterus. There was no cervical, supraclavicular, axillary, or inguinal lymphadenopathy. Cardiac examination revealed a tachycardic rhythm, with no murmur. Neurologic examination was normal. A circular skin lesion (measuring 1 cm in diameter) with a central scab was noted below the left lateral malleolus.

Table 1.

Laboratory Data.
A chest radiograph was normal. An electrocardiogram showed sinus tachycardia and was otherwise normal. Levels of calcium, magnesium, lactate, total protein, globulin, amylase, and lipase were normal, as were the prothrombin time, partial-thromboplastin time, and white-cell differential count. Tests for hepatitis A virus antibody and hepatitis B virus surface antibody were positive. Screening blood tests for human immunodeficiency virus (HIV) antibody, hepatitis C virus antibody, and hepatitis B virus IgM antibody and surface antigen were negative. Other laboratory test results are shown in Table 1. Samples of the blood and urine were obtained for culture, and normal saline was administered intravenously.

Diagnostic tests were performed.

Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fever, thrombocytopenia, and elevated aminotransferase levels, along with the presence of an erythematous, maculopapular rash and a circular skin lesion with a central scab, suggest a tick-borne illness. The patient's location in Massachusetts and his frequent running in a marshy area near his home further support this diagnosis. The most common tick-borne illnesses in this area are Lyme disease, anaplasmosis, and babesiosis. However, the patient's lack of neurologic, joint, or genitourinary symptoms make Lyme disease less likely. Between anaplasmosis and babesiosis, the latter is more likely to cause the patient's severe thrombocytopenia. Therefore, the most likely diagnosis is babesiosis.""
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        ""content"": ""The patient's symptoms of fever, thrombocytopenia, and elevated aminotransferase levels, along with the presence of a circular skin lesion with a central scab, suggest a tick-borne illness. The patient's location in Massachusetts and his frequent running in marshy areas further support this diagnosis. The most common tick-borne illnesses in this area are Lyme disease, babesiosis, and anaplasmosis. The patient's negative screening for other infectious diseases such as HIV and hepatitis C also support a tick-borne illness. The presence of thrombocytopenia and elevated aminotransferase levels are more consistent with anaplasmosis than with Lyme disease or babesiosis.\n\nDiagnosis: Anaplasmosis.""
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        ""content"": ""The patient is a 45-year-old man who presents with fever, thrombocytopenia, and elevated aminotransferase levels. He also has a history of an erythematous, maculopapular rash on the scalp, and a circular skin lesion with a central scab below the left lateral malleolus. He lives in a wooded area in Massachusetts and runs in a marshy area near his home. The differential diagnosis for this patient includes Lyme disease, Ehrlichiosis, Babesiosis, and Rocky Mountain Spotted Fever. The patient's rash is not the characteristic \""bull's eye\"" rash of Lyme disease, making this less likely. Rocky Mountain Spotted Fever typically presents with a rash on the wrists and ankles, which this patient does not have, making this less likely. Babesiosis typically presents with hemolytic anemia, which this patient does not have, making this less likely. Ehrlichiosis is a tick-borne illness that presents with fever, thrombocytopenia, and elevated aminotransferase levels, which this patient has. It is also common in the area where the patient lives and exercises. \n\nDiagnosis:\nThe most likely diagnosis is Ehrlichiosis.""
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10.1056/NEJMcpc1800339,"Case 15-2018: An 83-Year-Old Woman with Nausea, Vomiting, and Confusion",,Digoxin toxicity.,Digoxin toxicity.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:An 83-year-old woman was admitted to this hospital in the winter because of nausea, vomiting, diarrhea, and confusion.

One week before admission, rhinorrhea, sore throat, and nonproductive cough developed. The patient felt feverish but did not measure her temperature at home. No family members or recent contacts had been ill. Two days before admission, nausea, vomiting, and diarrhea developed. One day before admission, the patient asked her daughter repetitive questions and appeared to not recognize family members. On the day of admission, the patient reported global weakness and was brought by her daughter to the emergency department of this hospital for evaluation.

In the emergency department, the patient reported no headache, changes in vision, chest pain, shortness of breath, or abdominal pain. She had a history of rheumatic heart disease, with mitral-valve stenosis and regurgitation, atrial fibrillation, and heart failure with a preserved ejection fraction of 60%. Other medical history included osteoporosis, compression fracture of thoracic vertebrae, and chronic kidney disease with a creatinine level of 1.2 mg per deciliter (106 _mol per liter; reference range, 0.6 to 1.5 mg per deciliter [53 to 133 _mol per liter]) and an estimated glomerular filtration rate (GFR) of 50 ml per minute per 1.73 m2 of body-surface area (reference range, >60) according to the Modification of Diet in Renal Disease (MDRD) formula. Fifteen years earlier, she had undergone open mitral-valve commissurotomy and ring annuloplasty, procedures that were complicated by the development of recurrent severe mitral-valve regurgitation, which led to pulmonary hypertension, right ventricular dilatation and hypokinesis, and severe tricuspid-valve regurgitation. Nine years earlier, she had undergone bioprosthetic mitral-valve replacement and tricuspid-valve reconstruction with annuloplasty, with placement of a permanent pacemaker for persistent atrial fibrillation with bradycardia. Eight years earlier, transthoracic echocardiography had revealed a well-seated prosthetic mitral valve, an annular ring in the tricuspid position, mild tricuspid-valve regurgitation, and normal right ventricular size and function. In addition, 10 years earlier, a cholecystectomy had been performed.

The patient lived at home with one of her grown children, was independent in activities of daily living, and walked for 30 minutes daily. Medications included furosemide, spironolactone, metoprolol, digoxin, and warfarin. She took her daily medications from a pillbox organizer that her daughter filled on a weekly basis. Warfarin therapy was monitored monthly with measurement of the prothrombin time and international normalized ratio; almost all results had been in the therapeutic range. The patient was born in Uganda but had moved to New England when she was 64 years of age to live with her children. She did not smoke tobacco, drink alcohol, or use illicit drugs.

Table 1.

Laboratory Data.
On examination, the temperature was 36.9°C, the blood pressure 153/60 mm Hg, the pulse 64 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The weight was 39.2 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 18.7. The patient was cachectic and appeared ill. She was awake but lethargic, and she responded to questions with nonsensical answers in her native language. She intermittently followed simple one-step commands and could move her arms and legs. Results of cranial-nerve examinations were normal (although the function of the first cranial nerve was not tested). The mucous membranes were dry. Bowel sounds were present, and the abdomen was nondistended, soft, and nontender on palpation. The cardiac rhythm was irregularly irregular, with a loud S2 heart sound and a systolic murmur throughout the precordium; the jugular vein was nondistended. Crackles were present in the lower lung fields. There was no leg edema. The complete blood count was normal, as were results of liver-function tests and blood levels of calcium, phosphorus, and lipase. Urinalysis was normal, except for the presence of 1+ ketones (reference range, negative). Nucleic acid testing of a nasal-swab specimen for influenza A and B viruses and respiratory syncytial virus was negative. Other laboratory test results are shown in Table 1.

Figure 1.

Chest Radiographs.
Dr. Victorine V. Muse: Chest radiography (Figure 1) revealed wires associated with median sternotomy, a single-lead pacemaker on the left side of the heart, and evidence of mitral-valve and tricuspid-valve repairs. There was evidence of stable, massive, global cardiomegaly and mild interstitial pulmonary edema. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed prominent ventricles and sulci, as well as nonspecific, scattered periventricular white-matter hypodensities; there was no evidence of intracranial hemorrhage, large territorial infarction, or intracranial mass lesion.

Dr. Hoekzema: The patient was admitted to the hospital, and a diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:An 83-year-old woman was admitted to this hospital in the winter because of nausea, vomiting, diarrhea, and confusion.

One week before admission, rhinorrhea, sore throat, and nonproductive cough developed. The patient felt feverish but did not measure her temperature at home. No family members or recent contacts had been ill. Two days before admission, nausea, vomiting, and diarrhea developed. One day before admission, the patient asked her daughter repetitive questions and appeared to not recognize family members. On the day of admission, the patient reported global weakness and was brought by her daughter to the emergency department of this hospital for evaluation.

In the emergency department, the patient reported no headache, changes in vision, chest pain, shortness of breath, or abdominal pain. She had a history of rheumatic heart disease, with mitral-valve stenosis and regurgitation, atrial fibrillation, and heart failure with a preserved ejection fraction of 60%. Other medical history included osteoporosis, compression fracture of thoracic vertebrae, and chronic kidney disease with a creatinine level of 1.2 mg per deciliter (106 _mol per liter; reference range, 0.6 to 1.5 mg per deciliter [53 to 133 _mol per liter]) and an estimated glomerular filtration rate (GFR) of 50 ml per minute per 1.73 m2 of body-surface area (reference range, >60) according to the Modification of Diet in Renal Disease (MDRD) formula. Fifteen years earlier, she had undergone open mitral-valve commissurotomy and ring annuloplasty, procedures that were complicated by the development of recurrent severe mitral-valve regurgitation, which led to pulmonary hypertension, right ventricular dilatation and hypokinesis, and severe tricuspid-valve regurgitation. Nine years earlier, she had undergone bioprosthetic mitral-valve replacement and tricuspid-valve reconstruction with annuloplasty, with placement of a permanent pacemaker for persistent atrial fibrillation with bradycardia. Eight years earlier, transthoracic echocardiography had revealed a well-seated prosthetic mitral valve, an annular ring in the tricuspid position, mild tricuspid-valve regurgitation, and normal right ventricular size and function. In addition, 10 years earlier, a cholecystectomy had been performed.

The patient lived at home with one of her grown children, was independent in activities of daily living, and walked for 30 minutes daily. Medications included furosemide, spironolactone, metoprolol, digoxin, and warfarin. She took her daily medications from a pillbox organizer that her daughter filled on a weekly basis. Warfarin therapy was monitored monthly with measurement of the prothrombin time and international normalized ratio; almost all results had been in the therapeutic range. The patient was born in Uganda but had moved to New England when she was 64 years of age to live with her children. She did not smoke tobacco, drink alcohol, or use illicit drugs.

Table 1.

Laboratory Data.
On examination, the temperature was 36.9°C, the blood pressure 153/60 mm Hg, the pulse 64 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The weight was 39.2 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 18.7. The patient was cachectic and appeared ill. She was awake but lethargic, and she responded to questions with nonsensical answers in her native language. She intermittently followed simple one-step commands and could move her arms and legs. Results of cranial-nerve examinations were normal (although the function of the first cranial nerve was not tested). The mucous membranes were dry. Bowel sounds were present, and the abdomen was nondistended, soft, and nontender on palpation. The cardiac rhythm was irregularly irregular, with a loud S2 heart sound and a systolic murmur throughout the precordium; the jugular vein was nondistended. Crackles were present in the lower lung fields. There was no leg edema. The complete blood count was normal, as were results of liver-function tests and blood levels of calcium, phosphorus, and lipase. Urinalysis was normal, except for the presence of 1+ ketones (reference range, negative). Nucleic acid testing of a nasal-swab specimen for influenza A and B viruses and respiratory syncytial virus was negative. Other laboratory test results are shown in Table 1.

Figure 1.

Chest Radiographs.
Dr. Victorine V. Muse: Chest radiography (Figure 1) revealed wires associated with median sternotomy, a single-lead pacemaker on the left side of the heart, and evidence of mitral-valve and tricuspid-valve repairs. There was evidence of stable, massive, global cardiomegaly and mild interstitial pulmonary edema. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed prominent ventricles and sulci, as well as nonspecific, scattered periventricular white-matter hypodensities; there was no evidence of intracranial hemorrhage, large territorial infarction, or intracranial mass lesion.

Dr. Hoekzema: The patient was admitted to the hospital, and a diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of nausea, vomiting, diarrhea, and confusion, along with her history of heart disease and chronic kidney disease, suggest a possible electrolyte imbalance. The presence of ketones in her urine could indicate diabetic ketoacidosis, but this is less likely given that her blood glucose levels are not mentioned as being elevated. Her confusion could be due to a number of causes, including infection, metabolic derangement, or a neurological condition. However, her negative infectious workup and the nonspecific findings on her head CT make these less likely. The most likely diagnosis, given her symptoms and history, is hypernatremia due to dehydration. This is supported by her dry mucous membranes and the presence of ketones in her urine, which can occur with dehydration. Her confusion could be a symptom of severe hypernatremia.\n\nDiagnosis: Hypernatremia due to dehydration.""
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        ""content"": ""The patient's symptoms of nausea, vomiting, diarrhea, and confusion, along with her history of heart disease and chronic kidney disease, suggest a possible electrolyte imbalance. The presence of ketones in her urine could indicate diabetic ketoacidosis, but this is less likely given that her blood glucose levels are not mentioned as being elevated. Her confusion could be due to a number of causes, including infection, metabolic imbalance, or a neurological condition. However, her negative infectious workup and normal CT scan of the head make these less likely. The patient's symptoms began with rhinorrhea, sore throat, and nonproductive cough, suggesting a possible respiratory infection, but her negative nucleic acid testing for influenza A and B viruses and respiratory syncytial virus make this less likely. Given her history of heart disease and the presence of mild interstitial pulmonary edema on her chest radiograph, her symptoms could be due to congestive heart failure. However, her symptoms of gastrointestinal upset and confusion are more suggestive of a metabolic or electrolyte imbalance.\n\nDiagnosis: Electrolyte imbalance due to chronic kidney disease.""
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        ""content"": ""The patient is an elderly woman presenting with gastrointestinal symptoms (nausea, vomiting, diarrhea) and confusion. She also has a history of upper respiratory symptoms (rhinorrhea, sore throat, nonproductive cough). Her medical history is significant for rheumatic heart disease, mitral-valve stenosis and regurgitation, atrial fibrillation, heart failure, osteoporosis, compression fracture of thoracic vertebrae, and chronic kidney disease. The differential diagnosis for this patient includes infectious causes (such as gastroenteritis or a systemic infection), medication side effects or interactions, metabolic or electrolyte abnormalities, and cardiac causes (such as heart failure or arrhythmia). The patient's lab results show an elevated blood urea nitrogen (BUN) level and a slightly elevated creatinine level, indicating possible renal dysfunction. However, her estimated glomerular filtration rate (GFR) is within the normal range, suggesting that her kidneys are still functioning adequately. Her symptoms of confusion could be due to a urinary tract infection, but her urinalysis is normal except for the presence of ketones. The presence of ketones in the urine could indicate starvation, dehydration, or a metabolic state such as diabetic ketoacidosis. However, the patient does not have a history of diabetes, and her blood glucose level is normal. The patient's symptoms of nausea, vomiting, and diarrhea could be due to gastroenteritis, but this would not explain her confusion. Her confusion could be due to a medication side effect or interaction, but her medication list does not include any drugs that are commonly associated with confusion in the elderly. Her symptoms could also be due to a cardiac cause, such as heart failure or arrhythmia. However, her echocardiogram shows a well-seated prosthetic mitral valve, an annular ring in the tricuspid position, mild tricuspid-valve regurgitation, and normal right ventricular size and function, making a cardiac cause less likely. Given the patient's symptoms and lab results, the most likely diagnosis is a metabolic or electrolyte abnormality, possibly due to dehydration from her gastrointestinal symptoms.\n\nDiagnosis: Dehydration leading to metabolic or electrolyte abnormality.""
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10.1056/NEJMcpc1800337,"Case 14-2018: A 68-Year-Old Woman with a Rash, Hyponatremia, and Uveitis",,Rickettsiosis of the spotted fever group.,Indian tick typhus caused by Rickettsia conorii subspecies indica.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 68-year-old woman was admitted to this hospital during the winter because of a rash, hyponatremia, and anterior uveitis.

One month before admission, the patient traveled abroad. She spent a week in Sweden visiting family members, including her young grandchildren, and then she traveled to India 25 days before admission. She was well until 14 days before admission, when malaise and a nonpainful, nonpruritic, erythematous, maculopapular rash developed. The rash first appeared on the thighs; by the following day, it had become diffuse, involving the legs and feet (including the soles), arms and hands (including the palms), abdomen, chest, and flanks. On the fifth day of illness, the patient was seen by a physician in India. A complete blood count was reportedly normal. An unspecified medication was administered intramuscularly, and fexofenadine, ranitidine, a 9-day tapering course of prednisone, and a 5-day course of erythromycin were prescribed.

During the next 10 days, malaise persisted, the rash did not improve, and a mild, dry cough developed. The patient also noted mild blurred vision, which was worse in the left eye than in the right eye and was accompanied by mild photophobia and floaters with a spiderweb appearance. One or two episodes of diarrhea occurred each day, and she took loperamide.

Two days before admission, the patient returned to Sweden to visit family members. While she was there, arthralgias of the knees developed and the left eye became red. The patient then took a flight back to the United States, which landed on the day of admission; when she arrived, she presented to the emergency department of this hospital for evaluation.

In the emergency department, the patient reported fatigue, decreased appetite, diffuse myalgias, and mild, generalized swelling that was most prominent around the ankles. She had not noted fever or headache. She had a history of hypertension, hyperlipidemia, anxiety, depression, cataracts, and osteopenia, and she had undergone tonsillectomy during childhood, myomectomy and ovarian cystectomy 32 years before this admission, and allograft reconstruction of an injured right anterior cruciate ligament 11 years before this admission. The patient was taking lisinopril and had no known allergies to medications; amitriptyline had caused paresthesias, and she had had anxiety while she was taking oxycodone and acetaminophen in combination. Immunizations were reportedly current; in preparation for her trip to India, she had received an unspecified hepatitis vaccine.

The patient was married, lived with her husband in a suburban area of New England, and was retired. She had traveled extensively, including trips to northern and eastern Europe, Africa, and Central America. During her recent trip, she visited a national park in central India, where she received multiple mosquito bites. She observed a variety of wild animals but did not have contact with them. While she was in the park, approximately 23 days before admission, she found an engorged tick on her right leg. She reported that she does not drink alcohol or use illicit drugs and had stopped smoking tobacco 34 years earlier, with a history of 14 pack-years. There was a family history of diabetes mellitus, hypertension, coronary artery disease, and stroke.

Figure 1.

Clinical Photographs.
On examination, the patient had a labile affect; she appeared to be confused intermittently and made nonsensical statements occasionally. The temperature was 36.2°C, the pulse 88 beats per minute, the blood pressure 163/89 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. Mild photophobia was present, and there were flat patches of subconjunctival hemorrhage in the left eye and petechiae on the hard palate. She coughed with deep breathing, but the lungs were clear on auscultation. There was trace edema of the feet but no erythema, swelling, pain with movement, or warmth of the knees. There was a diffuse erythematous rash, which was macular and nonblanching on the lower legs and on the palms and soles (Figure 1) and was maculopapular and blanching, without coalescence, on the thighs, abdomen, chest, and arms. The remainder of the general examination was normal.

Table 1.

Laboratory Data.
The hemoglobin level, hematocrit, red-cell indexes, platelet count, anion gap, and results of renal-function tests were normal, as were blood levels of calcium, total protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, lactic acid, and thyrotropin; other laboratory test results are shown in Table 1. Urinalysis showed clear, yellow urine, with 2+ ketones, 2+ leukocyte esterase, a specific gravity of 1.015, and a pH of 5.0; on microscopic examination, there were 0 to 2 red cells per high-power field, 20 to 50 white cells per high-power field, and 1+ bacteria. An electrocardiogram showed a normal sinus rhythm, with sinus arrhythmia, poor R-wave progression, and minor, nonspecific ST-segment and T-wave abnormalities. Posteroanterior and lateral chest radiographs were normal.

Normal saline was administered. The patient was seen by an ophthalmologist. The visual acuity was 20/25 with eyeglasses. In the left eye, there was trace injection of the conjunctivas, with flat patches of subconjunctival hemorrhage inferiorly, temporally, and nasally. Slit-lamp examination revealed fine keratic precipitates on the left inferior cornea, with a single white cell in the right anterior chamber, 3 white cells per high-power field in the left anterior chamber, and 2+ nuclear sclerosis in both lenses. Indirect ophthalmoscopy revealed trace vitreous debris in both eyes. The remainder of the ophthalmologic examination was normal.

The patient was admitted to this hospital. Ophthalmic prednisolone and cyclopentolate (1% solutions) were administered in the left eye. Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 68-year-old woman was admitted to this hospital during the winter because of a rash, hyponatremia, and anterior uveitis.

One month before admission, the patient traveled abroad. She spent a week in Sweden visiting family members, including her young grandchildren, and then she traveled to India 25 days before admission. She was well until 14 days before admission, when malaise and a nonpainful, nonpruritic, erythematous, maculopapular rash developed. The rash first appeared on the thighs; by the following day, it had become diffuse, involving the legs and feet (including the soles), arms and hands (including the palms), abdomen, chest, and flanks. On the fifth day of illness, the patient was seen by a physician in India. A complete blood count was reportedly normal. An unspecified medication was administered intramuscularly, and fexofenadine, ranitidine, a 9-day tapering course of prednisone, and a 5-day course of erythromycin were prescribed.

During the next 10 days, malaise persisted, the rash did not improve, and a mild, dry cough developed. The patient also noted mild blurred vision, which was worse in the left eye than in the right eye and was accompanied by mild photophobia and floaters with a spiderweb appearance. One or two episodes of diarrhea occurred each day, and she took loperamide.

Two days before admission, the patient returned to Sweden to visit family members. While she was there, arthralgias of the knees developed and the left eye became red. The patient then took a flight back to the United States, which landed on the day of admission; when she arrived, she presented to the emergency department of this hospital for evaluation.

In the emergency department, the patient reported fatigue, decreased appetite, diffuse myalgias, and mild, generalized swelling that was most prominent around the ankles. She had not noted fever or headache. She had a history of hypertension, hyperlipidemia, anxiety, depression, cataracts, and osteopenia, and she had undergone tonsillectomy during childhood, myomectomy and ovarian cystectomy 32 years before this admission, and allograft reconstruction of an injured right anterior cruciate ligament 11 years before this admission. The patient was taking lisinopril and had no known allergies to medications; amitriptyline had caused paresthesias, and she had had anxiety while she was taking oxycodone and acetaminophen in combination. Immunizations were reportedly current; in preparation for her trip to India, she had received an unspecified hepatitis vaccine.

The patient was married, lived with her husband in a suburban area of New England, and was retired. She had traveled extensively, including trips to northern and eastern Europe, Africa, and Central America. During her recent trip, she visited a national park in central India, where she received multiple mosquito bites. She observed a variety of wild animals but did not have contact with them. While she was in the park, approximately 23 days before admission, she found an engorged tick on her right leg. She reported that she does not drink alcohol or use illicit drugs and had stopped smoking tobacco 34 years earlier, with a history of 14 pack-years. There was a family history of diabetes mellitus, hypertension, coronary artery disease, and stroke.

Figure 1.

Clinical Photographs.
On examination, the patient had a labile affect; she appeared to be confused intermittently and made nonsensical statements occasionally. The temperature was 36.2°C, the pulse 88 beats per minute, the blood pressure 163/89 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. Mild photophobia was present, and there were flat patches of subconjunctival hemorrhage in the left eye and petechiae on the hard palate. She coughed with deep breathing, but the lungs were clear on auscultation. There was trace edema of the feet but no erythema, swelling, pain with movement, or warmth of the knees. There was a diffuse erythematous rash, which was macular and nonblanching on the lower legs and on the palms and soles (Figure 1) and was maculopapular and blanching, without coalescence, on the thighs, abdomen, chest, and arms. The remainder of the general examination was normal.

Table 1.

Laboratory Data.
The hemoglobin level, hematocrit, red-cell indexes, platelet count, anion gap, and results of renal-function tests were normal, as were blood levels of calcium, total protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, lactic acid, and thyrotropin; other laboratory test results are shown in Table 1. Urinalysis showed clear, yellow urine, with 2+ ketones, 2+ leukocyte esterase, a specific gravity of 1.015, and a pH of 5.0; on microscopic examination, there were 0 to 2 red cells per high-power field, 20 to 50 white cells per high-power field, and 1+ bacteria. An electrocardiogram showed a normal sinus rhythm, with sinus arrhythmia, poor R-wave progression, and minor, nonspecific ST-segment and T-wave abnormalities. Posteroanterior and lateral chest radiographs were normal.

Normal saline was administered. The patient was seen by an ophthalmologist. The visual acuity was 20/25 with eyeglasses. In the left eye, there was trace injection of the conjunctivas, with flat patches of subconjunctival hemorrhage inferiorly, temporally, and nasally. Slit-lamp examination revealed fine keratic precipitates on the left inferior cornea, with a single white cell in the right anterior chamber, 3 white cells per high-power field in the left anterior chamber, and 2+ nuclear sclerosis in both lenses. Indirect ophthalmoscopy revealed trace vitreous debris in both eyes. The remainder of the ophthalmologic examination was normal.

The patient was admitted to this hospital. Ophthalmic prednisolone and cyclopentolate (1% solutions) were administered in the left eye. Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Rickettsial infection (Indian tick typhus)\n\nThe patient's history of travel to India, exposure to a tick, and the presence of a rash, hyponatremia, and anterior uveitis are all indicative of a rickettsial infection. Rickettsial infections are zoonotic diseases transmitted by arthropods such as ticks, fleas, and lice. The patient's symptoms of malaise, rash, cough, blurred vision, and arthralgias are consistent with a systemic rickettsial infection. The presence of anterior uveitis is also a common feature of rickettsial diseases. The patient's hyponatremia could be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is a known complication of rickettsial infections. The lack of improvement with antibiotics and steroids also suggests a disease that is not typically responsive to these treatments, such as a rickettsial infection.""
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        ""content"": ""The patient's symptoms of a rash, hyponatremia, and anterior uveitis, along with her recent travel history to India and exposure to a tick, suggest a tick-borne illness. The erythematous, maculopapular rash that spread to include the palms and soles is characteristic of a rickettsial infection, such as Rocky Mountain spotted fever or Mediterranean spotted fever. However, these conditions are typically associated with a high fever, which this patient did not report. The patient's hyponatremia could be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which can be caused by pulmonary disorders, CNS disorders, malignancies, and certain drugs, but can also be seen in some infections. The anterior uveitis could be a manifestation of a systemic infection or an autoimmune condition, but in the context of the patient's other symptoms and travel history, it is more likely related to an infectious process. The patient's confusion and labile affect could be due to encephalitis, which can be caused by a variety of pathogens, including those transmitted by ticks. Given all these factors, the most likely diagnosis is a tick-borne illness, possibly a rickettsial infection.\n\nDiagnosis: Tick-borne illness, possibly a rickettsial infection.""
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}","Tick-borne illness, possibly a rickettsial infection",Y,"{
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        ""content"": ""The patient is a 68-year-old woman who presents with a rash, hyponatremia, and anterior uveitis. She has a recent travel history to Sweden and India. The differential diagnosis for this patient includes tick-borne diseases, viral exanthems, drug reactions, and autoimmune diseases. The patient's rash is described as a nonpainful, nonpruritic, erythematous, maculopapular rash that first appeared on the thighs and then became diffuse. This is not characteristic of a drug reaction, which would typically present as a morbilliform rash. The patient also does not have a recent history of starting any new medications, making a drug reaction less likely. The patient's symptoms of malaise, dry cough, blurred vision, photophobia, floaters, and diarrhea could be consistent with a viral exanthem. However, her symptoms have persisted for 14 days, which is longer than the typical duration of a viral exanthem. The patient's symptoms could also be consistent with an autoimmune disease such as lupus. However, she does not have any other symptoms such as joint pain, oral ulcers, or photosensitivity that would suggest lupus. The patient has a history of finding an engorged tick on her right leg during her trip to India. This, along with her symptoms of malaise, rash, and anterior uveitis, is highly suggestive of a tick-borne disease. The patient's hyponatremia could also be explained by a tick-borne disease, as these diseases can cause SIADH, which would result in hyponatremia.\n\nDiagnosis: Tick-borne disease.""
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10.1056/NEJMcpc1800333,Case 13-2018: A 53-Year-Old Man with Cardiomyopathy and Recurrent Ventricular Tachycardia,,Giant-cell myocarditis.,Giant-cell myocarditis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 53-year-old man was admitted to this hospital because of shock and recurrent ventricular tachycardia after defibrillator placement for nonischemic cardiomyopathy.

The patient had been in his usual state of health until 4 weeks before this admission, when he was on vacation in the Caribbean and his wife noted that he was unresponsive, “gurgling,” and diaphoretic in the early morning. When he awoke, he reported chest pain, palpitations, and light-headedness. The patient was taken by ambulance to a local hospital, where the heart rate was 65 beats per minute, the blood pressure 100/56 mm Hg, and the oxygen saturation 100% while he was breathing oxygen through a nasal cannula at a rate of 2 liters per minute. The troponin T level was 1.56 ng per milliliter (normal range, <0.01), and the lactate level was 1.9 mmol per liter (17 mg per deciliter; normal range, 0.5 to 1.6 mmol per liter [5 to 14 mg per deciliter]). A complete blood count and levels of electrolytes, magnesium, calcium, and amylase were normal, as were results of tests of renal and thyroid function; a d-dimer level was undetectable. While the patient was in the local hospital, monomorphic ventricular tachycardia developed at a heart rate of 201 beats per minute; electrocardioversion resulted in restoration of sinus rhythm. Aspirin, clopidogrel, enoxaparin, rosuvastatin, amiodarone, and tirofiban were administered. The patient was transferred by air to a hospital in Florida.

Figure 1.

Initial Cardiac Studies, Obtained at the Second Hospital.
On examination at the second hospital, the temperature was 36.8°C, the heart rate 57 beats per minute, the blood pressure 122/90 mm Hg, the respiratory rate 14 breaths per minute, and the oxygen saturation 99% while the patient was breathing oxygen through a nasal cannula at a rate of 2 liters per minute. The remainder of the examination was normal. The blood troponin I level was 116.00 ng per milliliter (normal range, ≤0.05). A complete blood count, results of renal-function tests, levels of electrolytes and thyrotropin, and the prothrombin and partial-thromboplastin times were normal. An electrocardiogram (Figure 1A) showed sinus bradycardia, a ventricular ectopic beat, first-degree atrioventricular delay, and delayed intraventricular conduction. Aspirin, amiodarone, enoxaparin, and atorvastatin were administered. Ventricular tachycardia recurred at a heart rate of 176 beats per minute. Despite the administration of an intravenous bolus of amiodarone, ventricular tachycardia persisted. Electrocardioversion restored sinus rhythm. The patient was admitted to the hospital, and cardiac studies were performed.

Coronary angiography revealed no evidence of obstructive coronary disease. On ventriculography, the left ventricle was mildly and diffusely hypokinetic, and the left ventricular end-diastolic pressure was 22 mm Hg (normal range, 8 to 15). Transthoracic echocardiography (Figure 1B) revealed a dilated left ventricle with an end-diastolic dimension of 60 mm (normal range, 42 to 58) and an ejection fraction of 35% (normal range, 55 to 70); there was diffuse hypokinesis that was most notable in the inferior and septal territories, mildly increased wall thickness, and mild mitral regurgitation (see Video 1, available with the full text of this article at NEJM.org).

Dr. Sandeep S. Hedgire: Cardiac magnetic resonance imaging (MRI) confirmed the septal hypokinesis and revealed moderate left ventricular dilatation with an ejection fraction of 43%, as well as mild right ventricular dilatation with an ejection fraction of 36% (see Videos 2 and 3, available at NEJM.org). The left ventricular myocardium was normal in thickness. T2-weighted images (Figure 1C) showed marked myocardial edema that was most prominent in the interventricular septum. The ratio of signal in the myocardium to signal in the skeletal muscle was elevated, at 2.4 (normal range, ≤1.9), a finding compatible with edema. Images with late gadolinium enhancement (Figure 1D and 1E) showed patchy, nodular foci in the midwall and subepicardium of the septum and in the inferolateral wall of the left ventricle, with minimal extension into the subendocardium of the anterior segment at the midventricular level. The myocardial edema and pattern of late gadolinium enhancement fulfilled the Lake Louise criteria for the diagnosis of acute myocarditis.1,2

Dr. Churchill: Additional laboratory test results included negative nucleic acid amplification tests of the blood for DNA of adenovirus, Chlamydophila pneumoniae, cytomegalovirus, enterovirus, and Mycoplasma pneumoniae, as well as negative nucleic acid amplification tests of a nasopharyngeal swab for DNA of Bordetella pertussis, coronavirus, influenza, parainfluenza, metapneumovirus, respiratory syncytial virus, and rhinovirus. In addition, serologic testing was negative for antibodies to coxsackievirus, human immunodeficiency virus types 1 and 2, Lyme disease, and Trypanosoma cruzi, as well as for IgM antibodies to cytomegalovirus, Epstein–Barr virus viral capsid antigen, and parvovirus. Aspirin, metoprolol succinate, and amiodarone were prescribed, and the patient was discharged with a wearable defibrillator vest after a follow-up visit had been scheduled at this hospital.

Figure 2.

Subsequent Cardiac Studies, Obtained at This Hospital.
Ten days before this admission, the patient had consultations at this hospital with a cardiologist specializing in the management of heart failure and an electrophysiologist. Vital signs were notable for a heart rate of 49 beats per minute and a blood pressure of 108/70 mm Hg; the examination was otherwise normal. An electrocardiogram (Figure 2A) showed sinus bradycardia and first-degree atrioventricular delay, as well as right bundle-branch block and a left anterior fascicular block (which together constitute bifascicular block). Aspirin was stopped, spironolactone was added, and placement of an implantable cardioverter–defibrillator (ICD) was scheduled.

Table 1.

Laboratory Data.
On the morning of this admission, during placement of a dual-chamber ICD, episodes of ventricular tachycardia with varying foci were induced. These episodes were terminated with overdrive pacing. After the procedure, ventricular tachycardia developed, with a heart rate of 108 beats per minute (Figure 2B). The blood pressure was 88/53 mm Hg, and a lidocaine infusion was administered. Laboratory test results are shown in Table 1. During the next 10 hours, multiple additional episodes of monomorphic ventricular rhythms occurred, with the heart rate ranging from 90 to 140 beats per minute. The rate of lidocaine infusion was increased, and amiodarone was administered. Early in the morning of the second hospital day, ventricular tachycardia recurred, with associated dyspnea and a blood pressure of 66/40 mm Hg. Normal saline and norepinephrine were administered intravenously. Chest radiography revealed ICD leads in the appropriate position, and bedside echocardiography revealed no evidence of pericardial effusion. The ventricular tachycardia was terminated with antitachycardic pacing, and the ICD was reprogrammed to provide atrial pacing at a rate of 110 beats per minute. The patient was admitted to the cardiac intensive care unit (ICU).

A review of systems was notable for intermittent episodes of dyspnea. He had no dizziness, orthopnea, edema, or chest pain. He had a history of a kidney stone. Medications on admission to the cardiac ICU were metoprolol succinate, amiodarone, and spironolactone; he had no known allergies to medications. There was no family history of coronary artery disease, cardiomyopathy, heart failure, dysrhythmia, sudden death, or autoimmune disease. The patient was employed as a corporate executive. He had traveled extensively, including trips to urban areas in Mexico and Brazil during the previous 6 months. Three months before this admission, during a trip to Mexico, diarrhea had developed and spontaneously resolved after 2 weeks. He had two healthy adult children. He did not smoke tobacco, drink alcohol, or use illicit substances.

On examination in the cardiac ICU, the temperature was 36.8°C, the heart rate 91 beats per minute, the blood pressure 102/56 mm Hg, and the oxygen saturation 94% while the patient was breathing ambient air. He appeared to be comfortable and was conversant. The jugular venous pulse was 8 cm of water. The site of ICD placement in the left deltopectoral groove was slightly tender. Auscultation revealed a soft apical systolic murmur and a third heart sound, as well as scattered crackles in the lungs. The arms and legs were warm and had no edema. He had no rashes or lymphadenopathy. The rest of the examination was normal.

Results of blood tests of liver and thyroid function, tests for antinuclear antibodies, and serum protein electrophoresis were normal; other laboratory test results are shown in Table 1. An electrocardiogram showed a wide QRS complex (QRS duration, >240 msec) at a heart rate of 100 beats per minute, with a rightward axis. A transthoracic echocardiogram (Figure 2C) showed a dilated left ventricle with an end-diastolic dimension of 62 mm and an ejection fraction of 25%; there was diffuse dysfunction that was most notable in the anterior, septal, and inferior territories, as well as some thinning of the basal interventricular septum to 7 mm. In addition, there was mild hypokinesis of the right ventricle, biatrial enlargement, moderate mitral regurgitation, and mild-to-moderate tricuspid regurgitation (see Video 4, available at NEJM.org).

During the second hospital day, ventricular tachycardia persisted despite the administration of lidocaine and amiodarone; an infusion of esmolol was begun. Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 53-year-old man was admitted to this hospital because of shock and recurrent ventricular tachycardia after defibrillator placement for nonischemic cardiomyopathy.

The patient had been in his usual state of health until 4 weeks before this admission, when he was on vacation in the Caribbean and his wife noted that he was unresponsive, “gurgling,” and diaphoretic in the early morning. When he awoke, he reported chest pain, palpitations, and light-headedness. The patient was taken by ambulance to a local hospital, where the heart rate was 65 beats per minute, the blood pressure 100/56 mm Hg, and the oxygen saturation 100% while he was breathing oxygen through a nasal cannula at a rate of 2 liters per minute. The troponin T level was 1.56 ng per milliliter (normal range, <0.01), and the lactate level was 1.9 mmol per liter (17 mg per deciliter; normal range, 0.5 to 1.6 mmol per liter [5 to 14 mg per deciliter]). A complete blood count and levels of electrolytes, magnesium, calcium, and amylase were normal, as were results of tests of renal and thyroid function; a d-dimer level was undetectable. While the patient was in the local hospital, monomorphic ventricular tachycardia developed at a heart rate of 201 beats per minute; electrocardioversion resulted in restoration of sinus rhythm. Aspirin, clopidogrel, enoxaparin, rosuvastatin, amiodarone, and tirofiban were administered. The patient was transferred by air to a hospital in Florida.

Figure 1.

Initial Cardiac Studies, Obtained at the Second Hospital.
On examination at the second hospital, the temperature was 36.8°C, the heart rate 57 beats per minute, the blood pressure 122/90 mm Hg, the respiratory rate 14 breaths per minute, and the oxygen saturation 99% while the patient was breathing oxygen through a nasal cannula at a rate of 2 liters per minute. The remainder of the examination was normal. The blood troponin I level was 116.00 ng per milliliter (normal range, ≤0.05). A complete blood count, results of renal-function tests, levels of electrolytes and thyrotropin, and the prothrombin and partial-thromboplastin times were normal. An electrocardiogram (Figure 1A) showed sinus bradycardia, a ventricular ectopic beat, first-degree atrioventricular delay, and delayed intraventricular conduction. Aspirin, amiodarone, enoxaparin, and atorvastatin were administered. Ventricular tachycardia recurred at a heart rate of 176 beats per minute. Despite the administration of an intravenous bolus of amiodarone, ventricular tachycardia persisted. Electrocardioversion restored sinus rhythm. The patient was admitted to the hospital, and cardiac studies were performed.

Coronary angiography revealed no evidence of obstructive coronary disease. On ventriculography, the left ventricle was mildly and diffusely hypokinetic, and the left ventricular end-diastolic pressure was 22 mm Hg (normal range, 8 to 15). Transthoracic echocardiography (Figure 1B) revealed a dilated left ventricle with an end-diastolic dimension of 60 mm (normal range, 42 to 58) and an ejection fraction of 35% (normal range, 55 to 70); there was diffuse hypokinesis that was most notable in the inferior and septal territories, mildly increased wall thickness, and mild mitral regurgitation (see Video 1, available with the full text of this article at NEJM.org).

Dr. Sandeep S. Hedgire: Cardiac magnetic resonance imaging (MRI) confirmed the septal hypokinesis and revealed moderate left ventricular dilatation with an ejection fraction of 43%, as well as mild right ventricular dilatation with an ejection fraction of 36% (see Videos 2 and 3, available at NEJM.org). The left ventricular myocardium was normal in thickness. T2-weighted images (Figure 1C) showed marked myocardial edema that was most prominent in the interventricular septum. The ratio of signal in the myocardium to signal in the skeletal muscle was elevated, at 2.4 (normal range, ≤1.9), a finding compatible with edema. Images with late gadolinium enhancement (Figure 1D and 1E) showed patchy, nodular foci in the midwall and subepicardium of the septum and in the inferolateral wall of the left ventricle, with minimal extension into the subendocardium of the anterior segment at the midventricular level. The myocardial edema and pattern of late gadolinium enhancement fulfilled the Lake Louise criteria for the diagnosis of acute myocarditis.1,2

Dr. Churchill: Additional laboratory test results included negative nucleic acid amplification tests of the blood for DNA of adenovirus, Chlamydophila pneumoniae, cytomegalovirus, enterovirus, and Mycoplasma pneumoniae, as well as negative nucleic acid amplification tests of a nasopharyngeal swab for DNA of Bordetella pertussis, coronavirus, influenza, parainfluenza, metapneumovirus, respiratory syncytial virus, and rhinovirus. In addition, serologic testing was negative for antibodies to coxsackievirus, human immunodeficiency virus types 1 and 2, Lyme disease, and Trypanosoma cruzi, as well as for IgM antibodies to cytomegalovirus, Epstein–Barr virus viral capsid antigen, and parvovirus. Aspirin, metoprolol succinate, and amiodarone were prescribed, and the patient was discharged with a wearable defibrillator vest after a follow-up visit had been scheduled at this hospital.

Figure 2.

Subsequent Cardiac Studies, Obtained at This Hospital.
Ten days before this admission, the patient had consultations at this hospital with a cardiologist specializing in the management of heart failure and an electrophysiologist. Vital signs were notable for a heart rate of 49 beats per minute and a blood pressure of 108/70 mm Hg; the examination was otherwise normal. An electrocardiogram (Figure 2A) showed sinus bradycardia and first-degree atrioventricular delay, as well as right bundle-branch block and a left anterior fascicular block (which together constitute bifascicular block). Aspirin was stopped, spironolactone was added, and placement of an implantable cardioverter–defibrillator (ICD) was scheduled.

Table 1.

Laboratory Data.
On the morning of this admission, during placement of a dual-chamber ICD, episodes of ventricular tachycardia with varying foci were induced. These episodes were terminated with overdrive pacing. After the procedure, ventricular tachycardia developed, with a heart rate of 108 beats per minute (Figure 2B). The blood pressure was 88/53 mm Hg, and a lidocaine infusion was administered. Laboratory test results are shown in Table 1. During the next 10 hours, multiple additional episodes of monomorphic ventricular rhythms occurred, with the heart rate ranging from 90 to 140 beats per minute. The rate of lidocaine infusion was increased, and amiodarone was administered. Early in the morning of the second hospital day, ventricular tachycardia recurred, with associated dyspnea and a blood pressure of 66/40 mm Hg. Normal saline and norepinephrine were administered intravenously. Chest radiography revealed ICD leads in the appropriate position, and bedside echocardiography revealed no evidence of pericardial effusion. The ventricular tachycardia was terminated with antitachycardic pacing, and the ICD was reprogrammed to provide atrial pacing at a rate of 110 beats per minute. The patient was admitted to the cardiac intensive care unit (ICU).

A review of systems was notable for intermittent episodes of dyspnea. He had no dizziness, orthopnea, edema, or chest pain. He had a history of a kidney stone. Medications on admission to the cardiac ICU were metoprolol succinate, amiodarone, and spironolactone; he had no known allergies to medications. There was no family history of coronary artery disease, cardiomyopathy, heart failure, dysrhythmia, sudden death, or autoimmune disease. The patient was employed as a corporate executive. He had traveled extensively, including trips to urban areas in Mexico and Brazil during the previous 6 months. Three months before this admission, during a trip to Mexico, diarrhea had developed and spontaneously resolved after 2 weeks. He had two healthy adult children. He did not smoke tobacco, drink alcohol, or use illicit substances.

On examination in the cardiac ICU, the temperature was 36.8°C, the heart rate 91 beats per minute, the blood pressure 102/56 mm Hg, and the oxygen saturation 94% while the patient was breathing ambient air. He appeared to be comfortable and was conversant. The jugular venous pulse was 8 cm of water. The site of ICD placement in the left deltopectoral groove was slightly tender. Auscultation revealed a soft apical systolic murmur and a third heart sound, as well as scattered crackles in the lungs. The arms and legs were warm and had no edema. He had no rashes or lymphadenopathy. The rest of the examination was normal.

Results of blood tests of liver and thyroid function, tests for antinuclear antibodies, and serum protein electrophoresis were normal; other laboratory test results are shown in Table 1. An electrocardiogram showed a wide QRS complex (QRS duration, >240 msec) at a heart rate of 100 beats per minute, with a rightward axis. A transthoracic echocardiogram (Figure 2C) showed a dilated left ventricle with an end-diastolic dimension of 62 mm and an ejection fraction of 25%; there was diffuse dysfunction that was most notable in the anterior, septal, and inferior territories, as well as some thinning of the basal interventricular septum to 7 mm. In addition, there was mild hypokinesis of the right ventricle, biatrial enlargement, moderate mitral regurgitation, and mild-to-moderate tricuspid regurgitation (see Video 4, available at NEJM.org).

During the second hospital day, ventricular tachycardia persisted despite the administration of lidocaine and amiodarone; an infusion of esmolol was begun. Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""This is a 53-year-old man who presents with shock and recurrent ventricular tachycardia after defibrillator placement for nonischemic cardiomyopathy. The patient's history of travel to the Caribbean and Mexico, where he experienced diarrhea that resolved spontaneously, suggests a possible infectious etiology. However, extensive testing for infectious agents was negative. The patient's cardiac MRI showed myocardial edema and late gadolinium enhancement, fulfilling the Lake Louise criteria for acute myocarditis. The patient's recurrent ventricular tachycardia and the findings of diffuse hypokinesis and dilatation of the left ventricle on echocardiography are consistent with a diagnosis of myocarditis. The patient's symptoms and the results of the cardiac MRI and echocardiography are not consistent with ischemic heart disease, dilated cardiomyopathy, or hypertrophic cardiomyopathy. Therefore, the most likely diagnosis is myocarditis.\n\nDiagnosis: Myocarditis.""
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10.1056/NEJMcpc1800322,Case 12-2018: A 30-Year-Old Woman with Cardiac Arrest,,Tricyclic antidepressant overdose due to doxepin ingestion.,Tricyclic antidepressant overdose.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 30-year-old woman was brought to the emergency department of this hospital because of cardiac arrest.

On the morning of this presentation, the patient was found unresponsive in her bedroom. Her mother called emergency medical services (EMS) at 8:45 a.m. and initiated cardiopulmonary resuscitation (CPR), which was continued by first responders from the fire department on their arrival. The cardiac rhythm was assessed with an automated external defibrillator, and a shock was delivered. EMS personnel who could provide advanced life support arrived at 8:54 a.m. and found the patient to be pulseless. CPR was continued, and intraosseous access was established. Electrocardiography performed with an external monitor and defibrillator reportedly revealed wide-complex bradycardia. CPR was continued, the trachea was intubated, and sodium bicarbonate, epinephrine, and calcium chloride were administered intraosseously. Spontaneous circulation returned.

While the patient was being transported from her home to the ambulance, pulselessness recurred. CPR was resumed, and epinephrine was administered; a pulse was restored. At 9:16 a.m., the pulse was 94 beats per minute, the blood pressure 66/30 mm Hg, and the respiratory rate 7 breaths per minute. A peripheral intravenous catheter was inserted, and a bolus of normal saline was administered; thereafter, the blood pressure was 54/24 mm Hg. A continuous infusion of dopamine was begun, and the patient was transported to the emergency department of this hospital, arriving at 9:38 a.m.

On the patient’s arrival in the emergency department, the available history was limited. The patient’s mother reported that the patient drank alcohol in a binge pattern and had appeared to be intoxicated the previous evening but had seemed well at 7:45 a.m., before she went into her bedroom. The patient also smoked cigarettes and had a history of depression, anxiety, substance use disorder (including the use of alcohol, opioids, and cocaine), and skin abscesses due to methicillin-resistant Staphylococcus aureus. Current medications were unknown; a review of the electronic medical record revealed an allergy to amoxicillin–clavulanic acid. The patient lived in an urban area of New England with her mother, daughter, and cousin. She was unemployed.

On examination, the patient was obtunded and did not respond to noxious stimulation. The temperature was 35.9°C, the pulse 97 beats per minute, the blood pressure 60/24 mm Hg, the respiratory rate 25 breaths per minute, and the oxygen saturation 99% while she was receiving full mechanical ventilatory support (fraction of inspired oxygen, 1.00). The pupils were 6 mm in diameter and nonreactive to light. Corneal, oculocephalic, cough, and gag reflexes were absent. There were no spontaneous breaths over the ventilated breaths; breath sounds were equal in both lungs. Electrocardiography was performed.

Figure 1.

Initial Electrocardiogram.
Dr. David M. Dudzinski: The electrocardiogram (Figure 1) was notable for an irregular, wide-complex rhythm, with a QRS width of up to 220 msec. The differential diagnosis for a QRS complex of this width includes direct ventricular activation (ventricular tachycardia and pre-excitation), aberrant ventricular conduction, intramyocardial delay, severe cardiomyopathy, hypothermia, electrolyte abnormalities (including hyperkalemia), and toxic effects of drugs. The QRS complex had a broad positive R wave in lead V1, which is a morphologic feature resembling a right bundle-branch block. Other notable features of this QRS complex included a far rightward (“northwest”) frontal-plane axis, as well as a positive R wave in lead aVR, an abnormal finding that may indicate ventricular tachycardia, lead misplacement, dextrocardia, or certain toxidromes. The electrocardiogram also showed substantial prolongation of the corrected QT (QTc) interval, even after accounting for the effect of the wide QRS complex.

Table 1.

Laboratory Data.
Dr. Cleveland: Laboratory test results are shown in Table 1. Additional history was obtained, and a diagnosis and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 30-year-old woman was brought to the emergency department of this hospital because of cardiac arrest.

On the morning of this presentation, the patient was found unresponsive in her bedroom. Her mother called emergency medical services (EMS) at 8:45 a.m. and initiated cardiopulmonary resuscitation (CPR), which was continued by first responders from the fire department on their arrival. The cardiac rhythm was assessed with an automated external defibrillator, and a shock was delivered. EMS personnel who could provide advanced life support arrived at 8:54 a.m. and found the patient to be pulseless. CPR was continued, and intraosseous access was established. Electrocardiography performed with an external monitor and defibrillator reportedly revealed wide-complex bradycardia. CPR was continued, the trachea was intubated, and sodium bicarbonate, epinephrine, and calcium chloride were administered intraosseously. Spontaneous circulation returned.

While the patient was being transported from her home to the ambulance, pulselessness recurred. CPR was resumed, and epinephrine was administered; a pulse was restored. At 9:16 a.m., the pulse was 94 beats per minute, the blood pressure 66/30 mm Hg, and the respiratory rate 7 breaths per minute. A peripheral intravenous catheter was inserted, and a bolus of normal saline was administered; thereafter, the blood pressure was 54/24 mm Hg. A continuous infusion of dopamine was begun, and the patient was transported to the emergency department of this hospital, arriving at 9:38 a.m.

On the patient’s arrival in the emergency department, the available history was limited. The patient’s mother reported that the patient drank alcohol in a binge pattern and had appeared to be intoxicated the previous evening but had seemed well at 7:45 a.m., before she went into her bedroom. The patient also smoked cigarettes and had a history of depression, anxiety, substance use disorder (including the use of alcohol, opioids, and cocaine), and skin abscesses due to methicillin-resistant Staphylococcus aureus. Current medications were unknown; a review of the electronic medical record revealed an allergy to amoxicillin–clavulanic acid. The patient lived in an urban area of New England with her mother, daughter, and cousin. She was unemployed.

On examination, the patient was obtunded and did not respond to noxious stimulation. The temperature was 35.9°C, the pulse 97 beats per minute, the blood pressure 60/24 mm Hg, the respiratory rate 25 breaths per minute, and the oxygen saturation 99% while she was receiving full mechanical ventilatory support (fraction of inspired oxygen, 1.00). The pupils were 6 mm in diameter and nonreactive to light. Corneal, oculocephalic, cough, and gag reflexes were absent. There were no spontaneous breaths over the ventilated breaths; breath sounds were equal in both lungs. Electrocardiography was performed.

Figure 1.

Initial Electrocardiogram.
Dr. David M. Dudzinski: The electrocardiogram (Figure 1) was notable for an irregular, wide-complex rhythm, with a QRS width of up to 220 msec. The differential diagnosis for a QRS complex of this width includes direct ventricular activation (ventricular tachycardia and pre-excitation), aberrant ventricular conduction, intramyocardial delay, severe cardiomyopathy, hypothermia, electrolyte abnormalities (including hyperkalemia), and toxic effects of drugs. The QRS complex had a broad positive R wave in lead V1, which is a morphologic feature resembling a right bundle-branch block. Other notable features of this QRS complex included a far rightward (“northwest”) frontal-plane axis, as well as a positive R wave in lead aVR, an abnormal finding that may indicate ventricular tachycardia, lead misplacement, dextrocardia, or certain toxidromes. The electrocardiogram also showed substantial prolongation of the corrected QT (QTc) interval, even after accounting for the effect of the wide QRS complex.

Table 1.

Laboratory Data.
Dr. Cleveland: Laboratory test results are shown in Table 1. Additional history was obtained, and a diagnosis and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's history of substance use disorder, including alcohol, opioids, and cocaine, combined with her presentation of cardiac arrest, wide-complex bradycardia, and abnormal electrocardiogram findings, suggest a drug overdose. The electrocardiogram shows a wide QRS complex and a prolonged QTc interval, which can be caused by certain drugs, including tricyclic antidepressants and certain antiarrhythmics. The patient's history of depression and anxiety could suggest the use of such medications. The patient's nonreactive pupils and absent reflexes also suggest a central nervous system depressant, such as an opioid. \n\nDiagnosis: Drug overdose, likely involving a tricyclic antidepressant and/or opioid.""
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        ""content"": ""The patient is a 30-year-old woman with a history of substance use disorder, including alcohol, opioids, and cocaine, who was found unresponsive and in cardiac arrest. The differential diagnosis for this patient includes drug overdose, alcohol withdrawal, electrolyte abnormalities, and cardiac arrhythmias. The patient's history of substance use disorder, including opioids and cocaine, makes drug overdose a likely possibility. The patient's EKG shows a wide-complex rhythm with a QRS width of up to 220 msec, which could be due to toxic effects of drugs. The patient's lab results show a high anion gap metabolic acidosis, which could be due to lactic acidosis from poor tissue perfusion during cardiac arrest, or could be due to toxic ingestion such as methanol or ethylene glycol. However, the patient's history does not suggest access to these substances. The patient's blood alcohol level was elevated, but not to a level typically associated with loss of consciousness. The patient's urine drug screen was positive for opioids and cocaine. Given the patient's history of substance use disorder, the findings on EKG, and the positive urine drug screen, the most likely diagnosis is drug overdose.\n\nDiagnosis: Drug overdose.""
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10.1056/NEJMcpc1800323,"Case 11-2018: A 48-Year-Old Woman with Recurrent Venous Thromboembolism and Pulmonary Artery Aneurysm
List of authors.",,Pulmonary artery aneurysm that was most likely due to the Hughes–Stovin syndrome.,,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 48-year-old woman with a history of venous thromboembolism was seen in the pulmonary clinic of this hospital because of cough and decreased exercise tolerance.

Fifteen months before this presentation, at another hospital, the patient received a diagnosis of deep venous thrombosis of the right leg and segmental and subsegmental pulmonary embolism in both lower lobes. Blood tests for a factor V Leiden mutation and a prothrombin gene mutation were reportedly negative, as were tests for antiphospholipid, anticardiolipin, and _2-glycoprotein antibodies; the blood level of protein S was reportedly low. Treatment with warfarin was initiated. After 3 months of treatment, the patient had persistent cough and dyspnea on exertion, and repeat imaging studies were obtained.

Figure 1.

CT Angiogram of the Chest.
Dr. Shaunagh McDermott: Twelve months before this presentation, computed tomographic (CT) angiography of the chest was performed at the other hospital. There was pulmonary embolism in the right lung, with occlusion of the interlobar pulmonary artery that extended into the middle and lower lobes, including segmental arteries. There was also a new focal dilatation (1.1 cm in diameter) of the pulmonary artery in the left lower lobe, as well as a new small right pleural effusion (Figure 1).

Dr. Zaidi: Warfarin was discontinued, and treatment with apixaban was initiated. After 6 months of treatment, additional imaging studies were obtained.

Dr. McDermott: Six months before this presentation, CT angiography of the chest was performed at the other hospital. A large pulmonary embolus occluded the distal right main pulmonary artery, and the previously identified pulmonary emboli had not resolved. The dilatation of the pulmonary artery in the left lower lobe, which contained a thrombus, had not changed.

Dr. Zaidi: Because additional thromboembolic events had occurred while the patient was receiving apixaban, this medication was discontinued. Treatment with therapeutic subcutaneous enoxaparin sodium was initiated, after which the results of an anti–factor Xa assay were reportedly within the therapeutic range. After 4 months of treatment, repeat imaging studies were obtained.

Dr. McDermott: Two months before this presentation, CT angiography of the chest was performed at the other hospital. The right main pulmonary artery was completely occluded by thromboembolic material. There were several areas of consolidation that most likely represented evolving infarcts, as well as a thrombosed subsegmental artery in the left lower lobe in the area of the previously identified dilatation.

Dr. Zaidi: Transthoracic echocardiography was performed. The left ventricular ejection fraction was 55%, and the atria and right ventricle were of normal size and function. A ventilation–perfusion scan revealed a complete absence of perfusion to the right lung and multiple wedge-shaped perfusion defects at the left lung base. The patient was referred to the pulmonary clinic of this hospital for further evaluation.

On evaluation, the patient reported weight loss of 18 kg during the previous 3 months but no fever, night sweats, hemoptysis, oral ulcers, genital ulcers, rashes, or eye pain or redness. She had no known exposures to tuberculosis. She had a history of hypothyroidism and seizure disorder. Medications included subcutaneous enoxaparin sodium, levothyroxine, levetiracetam, and phenytoin. The patient reported consistent use of subcutaneous enoxaparin sodium, and the results of an anti–factor Xa assay were reportedly in the therapeutic range.

The patient resided in New England and had traveled to Florida during the year before this evaluation. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had diabetes; there was no family history of pulmonary disease, lung cancer, pulmonary embolism, or deep venous thrombosis.

On physical examination, the temperature was 36.9°C, the blood pressure 102/62 mm Hg in both arms, the pulse 96 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The weight was 48 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 17.5. The patient was breathing comfortably. Both lungs were clear. The first and second heart sounds were normal, without murmurs. The radial and dorsalis pedis pulses were normal. There was no clubbing or edema. The remainder of the physical examination was normal. Imaging studies were obtained to further evaluate the thrombus of the right main pulmonary artery.

Figure 2.

MRI of the Chest.
Dr. McDermott: Magnetic resonance imaging of the chest was performed before and after the administration of gadolinium. There was almost complete occlusion of the distal right main pulmonary artery and bilateral segmental and subsegmental pulmonary arteries that was consistent with thromboembolism. In the area of the occlusive thromboembolic material, there was enhancement of the wall of the main pulmonary artery, which was smooth and 2 mm in thickness (Figure 2). The main pulmonary artery was not dilated, and there was no evidence of strain on the right side of the heart. A new aneurysm (2.4 cm in diameter) of the pulmonary artery in the lateral basal segment of the left lower lobe contained a small amount of eccentric thromboembolic material. There were enlarging pulmonary infarcts in the right lung with a small amount of adjacent loculated pleural fluid.

Dr. Zaidi: The patient was admitted to this hospital for further evaluation. Blood levels of electrolytes and glucose, the complete blood count and differential count, and results of renal- and liver-function tests were normal. Assays for antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative, as were tests for human immunodeficiency virus type 1 and type 2 antibodies and type 1 p24 antigen. Blood cultures showed no growth. Screening for antitreponemal antibodies and an interferon-_ release assay for tuberculosis were negative, as were the results of a blood test for galactomannan antigen (negative index value, <5.0). The 1,3-beta-d-glucan level was less than 31 pg per milliliter (reference range, <60), the erythrocyte sedimentation rate was 69 mm per hour (reference range, 0 to 20), and the C-reactive protein level was 106 mg per liter (reference range, <8). Venous ultrasonography of both legs showed a partially occlusive deep venous thrombus (1.0 cm in length) in the right popliteal vein.

A procedure was performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:A 48-year-old woman with a history of venous thromboembolism was seen in the pulmonary clinic of this hospital because of cough and decreased exercise tolerance.

Fifteen months before this presentation, at another hospital, the patient received a diagnosis of deep venous thrombosis of the right leg and segmental and subsegmental pulmonary embolism in both lower lobes. Blood tests for a factor V Leiden mutation and a prothrombin gene mutation were reportedly negative, as were tests for antiphospholipid, anticardiolipin, and _2-glycoprotein antibodies; the blood level of protein S was reportedly low. Treatment with warfarin was initiated. After 3 months of treatment, the patient had persistent cough and dyspnea on exertion, and repeat imaging studies were obtained.

Figure 1.

CT Angiogram of the Chest.
Dr. Shaunagh McDermott: Twelve months before this presentation, computed tomographic (CT) angiography of the chest was performed at the other hospital. There was pulmonary embolism in the right lung, with occlusion of the interlobar pulmonary artery that extended into the middle and lower lobes, including segmental arteries. There was also a new focal dilatation (1.1 cm in diameter) of the pulmonary artery in the left lower lobe, as well as a new small right pleural effusion (Figure 1).

Dr. Zaidi: Warfarin was discontinued, and treatment with apixaban was initiated. After 6 months of treatment, additional imaging studies were obtained.

Dr. McDermott: Six months before this presentation, CT angiography of the chest was performed at the other hospital. A large pulmonary embolus occluded the distal right main pulmonary artery, and the previously identified pulmonary emboli had not resolved. The dilatation of the pulmonary artery in the left lower lobe, which contained a thrombus, had not changed.

Dr. Zaidi: Because additional thromboembolic events had occurred while the patient was receiving apixaban, this medication was discontinued. Treatment with therapeutic subcutaneous enoxaparin sodium was initiated, after which the results of an anti–factor Xa assay were reportedly within the therapeutic range. After 4 months of treatment, repeat imaging studies were obtained.

Dr. McDermott: Two months before this presentation, CT angiography of the chest was performed at the other hospital. The right main pulmonary artery was completely occluded by thromboembolic material. There were several areas of consolidation that most likely represented evolving infarcts, as well as a thrombosed subsegmental artery in the left lower lobe in the area of the previously identified dilatation.

Dr. Zaidi: Transthoracic echocardiography was performed. The left ventricular ejection fraction was 55%, and the atria and right ventricle were of normal size and function. A ventilation–perfusion scan revealed a complete absence of perfusion to the right lung and multiple wedge-shaped perfusion defects at the left lung base. The patient was referred to the pulmonary clinic of this hospital for further evaluation.

On evaluation, the patient reported weight loss of 18 kg during the previous 3 months but no fever, night sweats, hemoptysis, oral ulcers, genital ulcers, rashes, or eye pain or redness. She had no known exposures to tuberculosis. She had a history of hypothyroidism and seizure disorder. Medications included subcutaneous enoxaparin sodium, levothyroxine, levetiracetam, and phenytoin. The patient reported consistent use of subcutaneous enoxaparin sodium, and the results of an anti–factor Xa assay were reportedly in the therapeutic range.

The patient resided in New England and had traveled to Florida during the year before this evaluation. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had diabetes; there was no family history of pulmonary disease, lung cancer, pulmonary embolism, or deep venous thrombosis.

On physical examination, the temperature was 36.9°C, the blood pressure 102/62 mm Hg in both arms, the pulse 96 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The weight was 48 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 17.5. The patient was breathing comfortably. Both lungs were clear. The first and second heart sounds were normal, without murmurs. The radial and dorsalis pedis pulses were normal. There was no clubbing or edema. The remainder of the physical examination was normal. Imaging studies were obtained to further evaluate the thrombus of the right main pulmonary artery.

Figure 2.

MRI of the Chest.
Dr. McDermott: Magnetic resonance imaging of the chest was performed before and after the administration of gadolinium. There was almost complete occlusion of the distal right main pulmonary artery and bilateral segmental and subsegmental pulmonary arteries that was consistent with thromboembolism. In the area of the occlusive thromboembolic material, there was enhancement of the wall of the main pulmonary artery, which was smooth and 2 mm in thickness (Figure 2). The main pulmonary artery was not dilated, and there was no evidence of strain on the right side of the heart. A new aneurysm (2.4 cm in diameter) of the pulmonary artery in the lateral basal segment of the left lower lobe contained a small amount of eccentric thromboembolic material. There were enlarging pulmonary infarcts in the right lung with a small amount of adjacent loculated pleural fluid.

Dr. Zaidi: The patient was admitted to this hospital for further evaluation. Blood levels of electrolytes and glucose, the complete blood count and differential count, and results of renal- and liver-function tests were normal. Assays for antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative, as were tests for human immunodeficiency virus type 1 and type 2 antibodies and type 1 p24 antigen. Blood cultures showed no growth. Screening for antitreponemal antibodies and an interferon-_ release assay for tuberculosis were negative, as were the results of a blood test for galactomannan antigen (negative index value, <5.0). The 1,3-beta-d-glucan level was less than 31 pg per milliliter (reference range, <60), the erythrocyte sedimentation rate was 69 mm per hour (reference range, 0 to 20), and the C-reactive protein level was 106 mg per liter (reference range, <8). Venous ultrasonography of both legs showed a partially occlusive deep venous thrombus (1.0 cm in length) in the right popliteal vein.

A procedure was performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Chronic thromboembolic pulmonary hypertension (CTEPH)\n\nThis patient has a history of venous thromboembolism and presents with cough and decreased exercise tolerance. She has been treated with anticoagulants but has had recurrent pulmonary emboli. The patient's symptoms and imaging findings are consistent with chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is a form of pulmonary hypertension caused by chronic thromboembolic occlusion of the pulmonary vasculature. The differential diagnosis for this patient includes recurrent venous thromboembolism, pulmonary embolism, and other causes of pulmonary hypertension such as left heart disease, lung disease, and idiopathic pulmonary arterial hypertension. However, the patient's history of recurrent pulmonary emboli despite anticoagulation, the imaging findings of pulmonary artery occlusion, and the absence of other causes of pulmonary hypertension make CTEPH the most likely diagnosis.""
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10.1056/NEJMcpc1712224,Case 10-2018: An 84-Year-Old Man with Painless Unilateral Testicular Swelling,,Mycobacterial epididymo-orchitis due to Mycobacterium tuberculosis.,Genitourinary tuberculosis.   Testicular lymphoma.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:An 84-year-old man was evaluated at this hospital because of painless right testicular swelling.

The patient had been in his usual state of health until 6 weeks before this evaluation, when he noted while showering that the right testicle was approximately 3 times larger than the left testicle. The testicle was soft and nontender on palpation, and the enlargement had not been present the previous day.

The next day, the patient was evaluated at a local urgent care clinic. He reported no trauma, heavy lifting, recent sexual intercourse, testicular or scrotal pain, abdominal or back pain, skin changes or rash, obstructive urinary symptoms, hematuria or dysuria, or discharge. He had no constitutional symptoms, such as fever, night sweats, or weight loss. On examination, the right testicle had a large, soft, mobile posterior mass; the left testicle was normal. A presumptive diagnosis of a hydrocele was made, and the patient was advised to use scrotal support and, if pain occurred, to take nonsteroidal antiinflammatory drugs. Testicular ultrasonography was scheduled for the following day.

Figure 1.

Initial Ultrasound Images.
Dr. HeiShun Yu: The next day, ultrasonography (Figure 1) revealed marked asymmetric enlargement and hypervascularity of the right testicle. A hypoechoic region in the mediastinum testis was most likely related to edema due to infection or inflammation. The epididymis was also enlarged and hypervascular. An associated complex hydrocele, with septations and internal debris, was present on the right side. These findings were compatible with right epididymo-orchitis. The left testicle had normal echotexture and no focal lesion. There was an incidental left varicocele.

Dr. Abers: A 10-day course of oral levofloxacin was prescribed. Six weeks later, at a follow-up visit with his primary care physician, the patient reported persistent testicular swelling. He noted that there had been a mild decrease in the swelling after he had completed the levofloxacin course but that the testicle continued to enlarge thereafter, causing inconvenience owing to its bulk and the pressure in the right groin, which made it difficult for him to sit and to flex his upper leg. There were no additional symptoms, such as pain or fever.

The patient had long-standing benign prostatic hypertrophy with associated nocturia, as well as Raynaud’s phenomenon, mild normocytic anemia, peptic ulcer disease, colonic diverticulosis, hypercholesterolemia, hearing loss, and cataracts. An episode of syncope had occurred after exercise on a hot and humid day 3 years earlier, and he had undergone left inguinal herniorrhaphy with mesh placement 13 years earlier. Medications were aspirin, omeprazole, tamsulosin, finasteride, nifedipine as needed for symptoms of Raynaud’s phenomenon, and pravastatin. The patient had no known allergies. He performed aerobic exercise daily. He was married, had no children, and had immigrated to the United States from Turkey when he was 20 years of age. He was a retired health care professional; he reported that he had had at least one negative tuberculin skin test in the past. More than 40 years earlier, he had smoked cigarettes for 5 years; he did not consume alcohol or use illicit drugs. He had traveled to Canada, Western Europe, and the Caribbean in the past. His mother had died in her 70s after a stroke, his father had lived beyond 90 years of age, a brother had prostatic hypertrophy, and a sister had multiple sclerosis. There was no family history of cancer.

On examination, the patient appeared well. The temperature was 36.3°C, the heart rate 54 beats per minute, the blood pressure 119/64 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. The weight was 72.3 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 28.3. A firm, nontender right scrotal mass (7 cm in diameter) was located in the posterior region, protruding superiorly to the external inguinal ring. The mass transmitted light on transillumination. The scrotal skin was normal, with no erythema or peau d’orange (orange peel) changes. The left testicle had changes consistent with a varicocele. The prostate was small and benign on palpation. There was no inguinal lymphadenopathy. The remainder of the examination was normal. Urinalysis showed yellow, clear urine, with a specific gravity of 1.011 (reference range, 1.001 to 1.035), a pH of 6.0 (reference range, 5.0 to 9.0), and no evidence of leukocyte esterase or occult blood. A culture of the urine was sterile.

Figure 2.

Additional Ultrasound Images.
Dr. Yu: Repeat testicular ultrasonography (Figure 2) revealed further enlargement of the right testicle. The right testicular volume was approximately 33 ml; it had been approximately 19 ml on an image obtained 6 weeks earlier. The hypoechoic region in the right mediastinum testis had increased in size. The right testicular parenchyma and epididymis remained hypervascular. Multiple new nonspecific hypoechoic areas were scattered throughout the remaining testicular parenchyma. The left testicle was normal.

Dr. Abers: A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case: An 84-year-old man was evaluated at this hospital because of painless right testicular swelling.

The patient had been in his usual state of health until 6 weeks before this evaluation, when he noted while showering that the right testicle was approximately 3 times larger than the left testicle. The testicle was soft and nontender on palpation, and the enlargement had not been present the previous day.

The next day, the patient was evaluated at a local urgent care clinic. He reported no trauma, heavy lifting, recent sexual intercourse, testicular or scrotal pain, abdominal or back pain, skin changes or rash, obstructive urinary symptoms, hematuria or dysuria, or discharge. He had no constitutional symptoms, such as fever, night sweats, or weight loss. On examination, the right testicle had a large, soft, mobile posterior mass; the left testicle was normal. A presumptive diagnosis of a hydrocele was made, and the patient was advised to use scrotal support and, if pain occurred, to take nonsteroidal antiinflammatory drugs. Testicular ultrasonography was scheduled for the following day.

Figure 1.

Initial Ultrasound Images.
Dr. HeiShun Yu: The next day, ultrasonography (Figure 1) revealed marked asymmetric enlargement and hypervascularity of the right testicle. A hypoechoic region in the mediastinum testis was most likely related to edema due to infection or inflammation. The epididymis was also enlarged and hypervascular. An associated complex hydrocele, with septations and internal debris, was present on the right side. These findings were compatible with right epididymo-orchitis. The left testicle had normal echotexture and no focal lesion. There was an incidental left varicocele.

Dr. Abers: A 10-day course of oral levofloxacin was prescribed. Six weeks later, at a follow-up visit with his primary care physician, the patient reported persistent testicular swelling. He noted that there had been a mild decrease in the swelling after he had completed the levofloxacin course but that the testicle continued to enlarge thereafter, causing inconvenience owing to its bulk and the pressure in the right groin, which made it difficult for him to sit and to flex his upper leg. There were no additional symptoms, such as pain or fever.

The patient had long-standing benign prostatic hypertrophy with associated nocturia, as well as Raynaud’s phenomenon, mild normocytic anemia, peptic ulcer disease, colonic diverticulosis, hypercholesterolemia, hearing loss, and cataracts. An episode of syncope had occurred after exercise on a hot and humid day 3 years earlier, and he had undergone left inguinal herniorrhaphy with mesh placement 13 years earlier. Medications were aspirin, omeprazole, tamsulosin, finasteride, nifedipine as needed for symptoms of Raynaud’s phenomenon, and pravastatin. The patient had no known allergies. He performed aerobic exercise daily. He was married, had no children, and had immigrated to the United States from Turkey when he was 20 years of age. He was a retired health care professional; he reported that he had had at least one negative tuberculin skin test in the past. More than 40 years earlier, he had smoked cigarettes for 5 years; he did not consume alcohol or use illicit drugs. He had traveled to Canada, Western Europe, and the Caribbean in the past. His mother had died in her 70s after a stroke, his father had lived beyond 90 years of age, a brother had prostatic hypertrophy, and a sister had multiple sclerosis. There was no family history of cancer.

On examination, the patient appeared well. The temperature was 36.3°C, the heart rate 54 beats per minute, the blood pressure 119/64 mm Hg, and the oxygen saturation 98% while he was breathing ambient air. The weight was 72.3 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 28.3. A firm, nontender right scrotal mass (7 cm in diameter) was located in the posterior region, protruding superiorly to the external inguinal ring. The mass transmitted light on transillumination. The scrotal skin was normal, with no erythema or peau d’orange (orange peel) changes. The left testicle had changes consistent with a varicocele. The prostate was small and benign on palpation. There was no inguinal lymphadenopathy. The remainder of the examination was normal. Urinalysis showed yellow, clear urine, with a specific gravity of 1.011 (reference range, 1.001 to 1.035), a pH of 6.0 (reference range, 5.0 to 9.0), and no evidence of leukocyte esterase or occult blood. A culture of the urine was sterile.

Figure 2.

Additional Ultrasound Images.
Dr. Yu: Repeat testicular ultrasonography (Figure 2) revealed further enlargement of the right testicle. The right testicular volume was approximately 33 ml; it had been approximately 19 ml on an image obtained 6 weeks earlier. The hypoechoic region in the right mediastinum testis had increased in size. The right testicular parenchyma and epididymis remained hypervascular. Multiple new nonspecific hypoechoic areas were scattered throughout the remaining testicular parenchyma. The left testicle was normal.

Dr. Abers: A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with painless right testicular swelling that has persisted for 6 weeks. The swelling was initially thought to be a hydrocele, but did not respond to treatment and continued to enlarge. The patient's ultrasound showed marked asymmetric enlargement and hypervascularity of the right testicle, with a hypoechoic region in the mediastinum testis likely related to edema due to infection or inflammation. However, the patient did not respond to antibiotics, suggesting that the cause is not infectious. The patient's age and the painless, progressive nature of the swelling are suggestive of testicular cancer. \n\nTesticular cancer.""
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        ""content"": ""The patient is an elderly man presenting with painless right testicular swelling. The differential diagnosis for this patient includes hydrocele, epididymo-orchitis, testicular torsion, and testicular cancer. The patient's initial presentation was suggestive of a hydrocele, which is a fluid-filled sac around a testicle that causes swelling in the scrotum. However, the patient's symptoms did not improve with conservative management, making this diagnosis less likely. Epididymo-orchitis, an inflammation of the testicle and epididymis, was also considered, but the patient did not have any symptoms of infection such as fever or pain, and his condition did not improve with antibiotics. Testicular torsion, a twisting of the spermatic cord that cuts off the blood supply to the testicle, is unlikely given the patient's age and lack of acute pain. The patient's age, the painless nature of the swelling, and the continued growth of the mass despite treatment are all suggestive of testicular cancer. The ultrasound findings of an enlarged testicle with multiple hypoechoic areas also support this diagnosis.\n\nDiagnosis: Testicular cancer.""
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10.1056/NEJMcpc1800321,Case 9-2018: A 55-Year-Old Man with HIV Infection and a Mass on the Right Side of the Face,,Burkitt-like lymphoma with 11q aberrations.,Lymphoma,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:      A 55-year-old man with Crohn’s disease and a new diagnosis of human immunodeficiency virus type 1 (HIV-1) infection was seen in the infectious diseases clinic of this hospital because of a mass on the right side of the face.

Fifteen days before the current evaluation, while the patient was undergoing extraction of carious teeth, a health care worker sustained a needlestick injury, which prompted evaluation of the patient for infections caused by bloodborne pathogens. Hepatitis C virus antibodies were not detected, but a rapid screening test for HIV antibodies was positive, as was a fourth-generation combination assay for HIV-1 and HIV type 2 (HIV-2) antibodies and HIV-1 p24 antigen. A supplemental Western blot assay confirmed the diagnosis of HIV-1. The plasma HIV-1 RNA viral load was 69,300 copies per milliliter, and the blood CD4+ T-cell count was 65 per cubic millimeter (reference range, 348 to 1456). The patient was referred to the infectious diseases clinic of this hospital for treatment.

Eight days later, 1 week before the current evaluation, the patient was seen in the infectious diseases clinic. He reported that he had lost approximately 18 kg during the past 2 years, that he had chronic orodental pain and a chronic cough at night, and that the skin on his forehead, cheeks, and chest was peeling. He had Crohn’s disease, for which a total colectomy had been performed during childhood; he had been evaluated on multiple occasions during the past year for increased ostomy output and dehydration. He had no known history of sexually transmitted infections.

Fourteen years earlier, the patient had undergone fine-needle aspiration of an enlarged lymph node on the right side of the neck. Cytologic examination of the aspirate revealed findings consistent with reactive hyperplasia, with no evidence of a monoclonal B-cell or unusual T-cell population. Nineteen months before the current evaluation, an excisional biopsy of a mass on the right side of the neck had been performed. Histopathological examination of the biopsy specimen revealed an enlarged lymph node with florid follicular and paracortical hyperplasia.

The patient took diazepam and had no known allergies to medications. He resided in an urban area of New England. He was retired and had previously worked for the government. He did not smoke tobacco, drink alcohol, or use illicit drugs. He reported that he had never had sex but that he had been assaulted in the past. His mother had had lung cancer, and his father had had congestive heart failure.

Table 1.

Laboratory Data.
On examination in the clinic, the patient appeared anxious. The vital signs were normal, and the weight was 75.7 kg; 2 years earlier, the weight had been 93.2 kg. The maxilla was edentulous, and the few remaining mandibular teeth appeared carious. The abdomen was scaphoid, with an ostomy in the right lower quadrant, and the skin on the face and chest was erythematous and peeling; the remainder of the examination was normal. The anion gap and blood levels of glucose, calcium, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, vitamin B12, folic acid, testosterone, and glycated hemoglobin were normal, as were the results of renal-function tests; other laboratory test results are shown in Table 1. Topical ketoconazole–based shampoo, trimethoprim–sulfamethoxazole, and a fixed-dose formulation of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide were prescribed.

One week later, the patient returned to the infectious diseases clinic for follow-up (the current evaluation) and reported that a lump had developed on the right side of his face. He had adhered to the prescribed regimen, and his appetite had increased during the past week. On examination, the vital signs were normal, and the weight was 76.7 kg. At the angle of the right mandible, there was a firm, fixed, tender mass measuring 0.5 cm in diameter, with no overlying erythema or warmth. The erythema of the skin on the face and chest had decreased; the remainder of the examination was unchanged. An interferon-_ release assay for a cell-mediated immune response to Mycobacterium tuberculosis was negative. Chest radiography revealed minimal linear and reticular opacities in the right middle lobe, lingula, and left lower lobe; these findings had not changed from previous examinations. A follow-up appointment was arranged for the following week.

One week after this evaluation, repeat examination in the infectious diseases clinic revealed that the size of the mass on the right side of the face had increased to 1 cm in diameter. One week later, the size of the mass had increased to 1.5 cm in diameter, and numbness of the right pinna had developed. Imaging studies were obtained.

Figure 1.

Imaging Studies.
Dr. Hillary R. Kelly: Computed tomography (CT) of the neck (Figure 1A and 1B) revealed asymmetric enlargement of the right parotid gland, with no surrounding inflammatory change. There was an ill-defined, central focus of hypoattenuation in the right parotid gland, a finding that raised concerns about a fluid collection or mass lesion. Scattered cervical lymph nodes were seen throughout the neck; these nodes were thought to be larger and more numerous than expected for an otherwise healthy 55-year-old patient but did not meet the size criteria for enlargement due to cancer. CT of the head revealed enlargement of the prepontine and premedullary cisterns and of the fourth ventricle, a finding that reflected disproportionate volume loss in the brain stem relative to the cerebral hemispheres. Magnetic resonance imaging (MRI) was recommended for further characterization of the facial mass.

MRI of the neck was performed after the administration of intravenous contrast material (Figure 1C through 1F). A large, multilobulated mass or confluent cluster of nodules occupied most of the deep and superficial lobes of the right parotid gland, extending through and widening the stylomandibular tunnel. There was a small rind of normal parotid parenchyma surrounding this mass. The mass had an isointense signal on T1-weighted imaging, restricted diffusion on diffusion-weighted imaging, and heterogeneous enhancement on contrast-enhanced imaging. There was a central focus of hypointense signal on T2-weighted imaging that corresponded to the focus of hypoattenuation that had been seen on the CT scan of the neck. The maximum dimensions of the mass were 4.2 cm transverse by 3.3 cm anteroposterior by 5.6 cm craniocaudal; the parotid gland was more enlarged than it had been on the CT scan. The lesion bowed the external carotid artery anteriorly and abutted the posterior border of the mandibular ramus; there was no evidence of cortical erosion or abnormal signal in the marrow. The fat adjacent to the stylomastoid foramen was preserved, and there was no abnormal enhancement along the intratemporal segment of the right facial nerve or along the auriculotemporal nerve that would suggest perineural spread. In addition, there were multiple enlarged cervical nodes bilaterally, findings consistent with those seen on the CT scan of the neck.

Dr. Goldstein: A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:     A 55-year-old man with Crohn’s disease and a new diagnosis of human immunodeficiency virus type 1 (HIV-1) infection was seen in the infectious diseases clinic of this hospital because of a mass on the right side of the face.

Fifteen days before the current evaluation, while the patient was undergoing extraction of carious teeth, a health care worker sustained a needlestick injury, which prompted evaluation of the patient for infections caused by bloodborne pathogens. Hepatitis C virus antibodies were not detected, but a rapid screening test for HIV antibodies was positive, as was a fourth-generation combination assay for HIV-1 and HIV type 2 (HIV-2) antibodies and HIV-1 p24 antigen. A supplemental Western blot assay confirmed the diagnosis of HIV-1. The plasma HIV-1 RNA viral load was 69,300 copies per milliliter, and the blood CD4+ T-cell count was 65 per cubic millimeter (reference range, 348 to 1456). The patient was referred to the infectious diseases clinic of this hospital for treatment.

Eight days later, 1 week before the current evaluation, the patient was seen in the infectious diseases clinic. He reported that he had lost approximately 18 kg during the past 2 years, that he had chronic orodental pain and a chronic cough at night, and that the skin on his forehead, cheeks, and chest was peeling. He had Crohn’s disease, for which a total colectomy had been performed during childhood; he had been evaluated on multiple occasions during the past year for increased ostomy output and dehydration. He had no known history of sexually transmitted infections.

Fourteen years earlier, the patient had undergone fine-needle aspiration of an enlarged lymph node on the right side of the neck. Cytologic examination of the aspirate revealed findings consistent with reactive hyperplasia, with no evidence of a monoclonal B-cell or unusual T-cell population. Nineteen months before the current evaluation, an excisional biopsy of a mass on the right side of the neck had been performed. Histopathological examination of the biopsy specimen revealed an enlarged lymph node with florid follicular and paracortical hyperplasia.

The patient took diazepam and had no known allergies to medications. He resided in an urban area of New England. He was retired and had previously worked for the government. He did not smoke tobacco, drink alcohol, or use illicit drugs. He reported that he had never had sex but that he had been assaulted in the past. His mother had had lung cancer, and his father had had congestive heart failure.

Table 1.

Laboratory Data.
On examination in the clinic, the patient appeared anxious. The vital signs were normal, and the weight was 75.7 kg; 2 years earlier, the weight had been 93.2 kg. The maxilla was edentulous, and the few remaining mandibular teeth appeared carious. The abdomen was scaphoid, with an ostomy in the right lower quadrant, and the skin on the face and chest was erythematous and peeling; the remainder of the examination was normal. The anion gap and blood levels of glucose, calcium, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, vitamin B12, folic acid, testosterone, and glycated hemoglobin were normal, as were the results of renal-function tests; other laboratory test results are shown in Table 1. Topical ketoconazole–based shampoo, trimethoprim–sulfamethoxazole, and a fixed-dose formulation of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide were prescribed.

One week later, the patient returned to the infectious diseases clinic for follow-up (the current evaluation) and reported that a lump had developed on the right side of his face. He had adhered to the prescribed regimen, and his appetite had increased during the past week. On examination, the vital signs were normal, and the weight was 76.7 kg. At the angle of the right mandible, there was a firm, fixed, tender mass measuring 0.5 cm in diameter, with no overlying erythema or warmth. The erythema of the skin on the face and chest had decreased; the remainder of the examination was unchanged. An interferon-_ release assay for a cell-mediated immune response to Mycobacterium tuberculosis was negative. Chest radiography revealed minimal linear and reticular opacities in the right middle lobe, lingula, and left lower lobe; these findings had not changed from previous examinations. A follow-up appointment was arranged for the following week.

One week after this evaluation, repeat examination in the infectious diseases clinic revealed that the size of the mass on the right side of the face had increased to 1 cm in diameter. One week later, the size of the mass had increased to 1.5 cm in diameter, and numbness of the right pinna had developed. Imaging studies were obtained.

Figure 1.

Imaging Studies.
Dr. Hillary R. Kelly: Computed tomography (CT) of the neck (Figure 1A and 1B) revealed asymmetric enlargement of the right parotid gland, with no surrounding inflammatory change. There was an ill-defined, central focus of hypoattenuation in the right parotid gland, a finding that raised concerns about a fluid collection or mass lesion. Scattered cervical lymph nodes were seen throughout the neck; these nodes were thought to be larger and more numerous than expected for an otherwise healthy 55-year-old patient but did not meet the size criteria for enlargement due to cancer. CT of the head revealed enlargement of the prepontine and premedullary cisterns and of the fourth ventricle, a finding that reflected disproportionate volume loss in the brain stem relative to the cerebral hemispheres. Magnetic resonance imaging (MRI) was recommended for further characterization of the facial mass.

MRI of the neck was performed after the administration of intravenous contrast material (Figure 1C through 1F). A large, multilobulated mass or confluent cluster of nodules occupied most of the deep and superficial lobes of the right parotid gland, extending through and widening the stylomandibular tunnel. There was a small rind of normal parotid parenchyma surrounding this mass. The mass had an isointense signal on T1-weighted imaging, restricted diffusion on diffusion-weighted imaging, and heterogeneous enhancement on contrast-enhanced imaging. There was a central focus of hypointense signal on T2-weighted imaging that corresponded to the focus of hypoattenuation that had been seen on the CT scan of the neck. The maximum dimensions of the mass were 4.2 cm transverse by 3.3 cm anteroposterior by 5.6 cm craniocaudal; the parotid gland was more enlarged than it had been on the CT scan. The lesion bowed the external carotid artery anteriorly and abutted the posterior border of the mandibular ramus; there was no evidence of cortical erosion or abnormal signal in the marrow. The fat adjacent to the stylomastoid foramen was preserved, and there was no abnormal enhancement along the intratemporal segment of the right facial nerve or along the auriculotemporal nerve that would suggest perineural spread. In addition, there were multiple enlarged cervical nodes bilaterally, findings consistent with those seen on the CT scan of the neck.

Dr. Goldstein: A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of Crohn's disease and a recent diagnosis of HIV-1 infection. He presents with a mass on the right side of his face, which has been growing in size. Imaging studies reveal a large, multilobulated mass or confluent cluster of nodules occupying most of the deep and superficial lobes of the right parotid gland. Given the patient's immunocompromised status due to HIV-1 infection, the mass is likely due to an opportunistic infection or malignancy. The patient's history of Crohn's disease, a chronic inflammatory condition, may also predispose him to certain types of malignancies. The imaging characteristics of the mass, including its isointense signal on T1-weighted imaging, restricted diffusion on diffusion-weighted imaging, and heterogeneous enhancement on contrast-enhanced imaging, are suggestive of a neoplastic process. Therefore, the most likely diagnosis is a parotid gland tumor. However, the exact type of tumor (benign vs. malignant, primary vs. metastatic, specific histologic subtype) cannot be determined without further diagnostic testing, such as a biopsy. \n\nDiagnosis: Parotid gland tumor.""
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    {
      ""index"": 0,
      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient has a history of Crohn's disease and a recent diagnosis of HIV-1 infection. He presents with a mass on the right side of his face, which has been growing in size. Imaging studies reveal a large, multilobulated mass or confluent cluster of nodules occupying most of the deep and superficial lobes of the right parotid gland. Given the patient's immunocompromised status due to HIV-1 infection, the mass is likely due to an opportunistic infection or malignancy. The most common malignancies in the parotid gland are salivary gland tumors, but these are less likely in this case due to the patient's HIV status. Lymphomas are common in HIV patients and can present as a mass in the parotid gland. Therefore, the most likely diagnosis is a lymphoma, possibly a non-Hodgkin's lymphoma which is more common in HIV patients.\n\nDiagnosis: Non-Hodgkin's Lymphoma.""
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        ""content"": ""This is a 55-year-old man with a history of Crohn's disease and a recent diagnosis of HIV-1 infection. He presents with a mass on the right side of his face, weight loss, chronic orodental pain, chronic cough, and peeling skin on his forehead, cheeks, and chest. The differential diagnosis for this patient includes lymphoma, Kaposi's sarcoma, parotid gland tumor, and other opportunistic infections such as fungal or mycobacterial infections. The patient's history of HIV infection and low CD4+ T-cell count make him susceptible to opportunistic infections and malignancies. The patient's imaging studies reveal a large, multilobulated mass or confluent cluster of nodules in the right parotid gland. The mass has an isointense signal on T1-weighted imaging, restricted diffusion on diffusion-weighted imaging, and heterogeneous enhancement on contrast-enhanced imaging. These findings are suggestive of a neoplastic process. The patient's history of weight loss and chronic cough could also be indicative of a systemic malignancy. Given the patient's immunocompromised status, lymphoma is a strong possibility. Kaposi's sarcoma is less likely given the absence of the characteristic skin lesions. Parotid gland tumors are also a possibility, but these are less common in HIV-infected individuals compared to lymphoma. Fungal or mycobacterial infections could also present with a mass, but these would typically be associated with other systemic symptoms and signs of infection, which this patient does not have.\n\nDiagnosis: Lymphoma is the most likely diagnosis.""
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10.1056/NEJMcpc1712225,Case 8-2018: A 55-Year-Old Woman with Shock and Labile Blood Pressure,,Catecholamine-induced cardiotoxicity due to pheochromocytoma.,akotsubo cardiomyopathy and catecholamine-induced crisis due to pheochromocytoma.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:       A 55-year-old woman was transferred to this hospital for evaluation and treatment of cardiogenic shock.

Approximately 4 months before presentation, the patient was admitted to a hospital in her home state for “pounding” in her chest, nausea, and diaphoresis that persisted for 40 minutes after a routine jog. The heart rate was 65 beats per minute, and the blood pressure 138/72 mm Hg; the remainder of the examination was normal. Four serial electrocardiograms were reportedly normal, but the troponin I level was elevated, at 0.055 ng per milliliter, and 11 hours later, it had risen to 0.415 ng per milliliter (normal range, 0 to 0.045). Transthoracic echocardiography revealed normal biventricular function. Coronary angiography revealed no evidence of obstructive coronary artery disease; the left ventricular end-diastolic pressure was 5 mm Hg. After discharge (4 days after admission), cardiac magnetic resonance imaging (MRI) revealed normal biventricular function and size, with no evidence of myocardial edema or fibrosis. Aspirin and a beta blocker were prescribed for presumed exercise-related supraventricular tachycardia.

The symptoms did not recur, and the patient returned to jogging and stopped taking the beta blocker. On the day before her transfer to this hospital, she was on a downhill-skiing trip in Vermont. In the morning, she felt fatigued. In the afternoon, palpitations, dyspnea, and weakness developed while she was at the top of a mountain; the ski patrol took her down the mountain, and the symptoms abated. In the evening, while she was at dinner, she had acute nausea and emesis followed by chest pain and dyspnea. She was taken to a local emergency department. The heart rate was 111 beats per minute, the blood pressure 115/81 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 84% while she was breathing ambient air. Auscultation revealed diffuse crackles in the lungs. The troponin I level was 11.000 ng per milliliter (normal range, 0 to 0.045), the N-terminal pro–B-type natriuretic peptide (NT-proBNP) level 15,159 pg per milliliter (normal range, 0 to 125), the lactate level 4.6 mmol per liter (41.0 mg per deciliter; normal range, 0.5 to 2.0 mmol per liter [4.5 to 18.0 mg per deciliter]), the venous blood pH 7.22 (normal range, 7.38 to 7.46), and the white-cell count 36,100 per cubic millimeter (normal range, 4500 to 11,000). Bedside cardiac ultrasonography revealed severe left ventricular dysfunction with apical ballooning. Intravenous infusions of heparin and furosemide were administered, and the patient was transferred by helicopter to a nearby tertiary care center for treatment of suspected cardiogenic shock.

On the patient’s arrival at the tertiary care center, the temperature was 37.2°C, the heart rate 143 beats per minute, the blood pressure 96/72 mm Hg, the respiratory rate 26 breaths per minute, and the oxygen saturation 84% while she was breathing ambient air and 88 to 94% while she was receiving oxygen through a nonrebreather face mask. On physical examination, she appeared fatigued and had jugular venous distention, diffuse crackles in the lungs, and cold arms and legs. The troponin I level was 4.790 ng per milliliter (normal range, <0.034), the white-cell count 30,240 per cubic millimeter (normal range, 4500 to 11,000), the arterial blood pH 7.08 (normal range, 7.35 to 7.45), the lactate level 5.9 mmol per liter (53 mg per deciliter; normal range, <2.0 mmol per liter [<18 mg per deciliter]), the NT-proBNP level 24,900 pg per milliliter (normal range, <300), and the creatinine level 1.41 mg per deciliter (125 _mol per liter; normal range for women, 0.52 to 1.04 mg per deciliter [46 to 92 _mol per liter]).

Chest radiography revealed diffuse pulmonary edema. Electrocardiography showed sinus tachycardia and T-wave inversions in leads V4 through V6. The trachea was intubated, and mechanical ventilation was initiated for respiratory failure. Transthoracic echocardiography revealed a left ventricular ejection fraction of 15% and left ventricular apical akinesis, as well as severe right ventricular apical dysfunction. Infusions of norepinephrine, dobutamine, epinephrine, amiodarone, propofol, midazolam, fentanyl, and sodium bicarbonate were administered. Empirical methylprednisolone was administered for presumed myocarditis. Coronary angiography revealed normal coronary arteries; the left ventricular end-diastolic pressure was 38 mm Hg. A percutaneous transaortic left ventricular assist device was placed. After the institution of mechanical circulatory support, the intravenous doses of norepinephrine, dobutamine, and epinephrine were tapered and eventually stopped. Hematuria developed, and the urine output declined. The blood pressure was labile, ranging from 60/40 to 140/110 mm Hg, and an infusion of sodium nitroprusside was administered for control of elevated blood pressure. The patient was transferred by helicopter to this hospital.

On the patient’s arrival at this hospital, additional history was obtained from her husband. She had a history of thyroid cancer (unknown pathologic subtype) that had been treated with thyroidectomy and radioactive iodine ablation. Medications included levothyroxine and a calcium supplement. The use of cefadroxil had caused the Stevens–Johnson syndrome. She did not smoke cigarettes, drink alcohol, or use illicit drugs. She was employed in health care, was married, and had one healthy daughter. Her maternal grandfather had died from myocardial infarction at 60 years of age, her father had had an aortic-valve replacement, and her mother had had lung cancer.

On examination, the temperature was 36.9°C, the heart rate 132 beats per minute, the blood pressure 105/72 mm Hg, and the oxygen saturation 96% while the patient was receiving oxygen through a mechanical ventilator (positive end-expiratory pressure, 12; tidal volume, 400 ml; fraction of inspired oxygen, 1.0; respiratory rate, 16 breaths per minute). The pupils were reactive to light in a symmetric but slightly sluggish manner. The patient was able to follow simple commands. She had no masses in the neck or exophthalmos. The jugular veins appeared distended. Auscultation of the chest revealed the hum of the ventricular assist device, distant tachycardic heart sounds, and scattered crackles in the lungs. The ventricular assist device had been secured in place by way of the left groin. She had 1+ pedal edema bilaterally and no rash or lymphadenopathy. A small amount of reddish brown urine was noted.

Table 1.

Laboratory Data.
Levels of thyrotropin, bilirubin, and alkaline phosphatase were normal; other test results are shown in Table 1. Urinalysis revealed 3+ blood. Tests of a nasopharyngeal swab for nucleic acids of influenza A and B and respiratory syncytial virus and for metapneumovirus antigens were negative, as was combination testing for antibodies to human immunodeficiency virus types 1 and 2 and p24 antigen.

Figure 1.

Electrocardiogram.
Dr. Ravi V. Shah: Electrocardiography showed sinus tachycardia, poor R-wave progression, T-wave inversions in leads V3 through V6 and in inferior leads, low QRS voltage, and a prolonged corrected QT (QTc) interval (Figure 1). Chest radiography revealed diffuse interstitial infiltrates, small bilateral pleural effusions, and the tip of the ventricular assist device projecting over the left ventricle. Transthoracic echocardiography revealed severe left ventricular systolic dysfunction, with an estimated ejection fraction of 20% and severe mid-to-apical hypokinesis, as well as right ventricular free-wall and apical dysfunction, no clinically significant valvular disease, and a small pericardial effusion (see Video 1, available with the full text of this article at NEJM.org). On echocardiography, the tip of the ventricular assist device was in the appropriate position in the left ventricle.

Dr. Roy: Shortly after the patient’s arrival at this hospital, hypotension again developed, and infusions of milrinone, epinephrine, and norepinephrine were administered. Femoral venoarterial extracorporeal life support was initiated to facilitate sufficient cardiac output, since the percutaneous ventricular assist device had provided insufficient support and caused increasing hemolysis.1 Continuous venovenous hemofiltration was initiated for anuria, fluid overload, and acidosis in the context of acute kidney injury. Methylprednisolone was administered intravenously.

During the first 3 hospital days, the blood pressure remained labile, with the systolic blood pressure ranging from 65 to 205 mm Hg, despite stable levels of sedation and extracorporeal life support. The patient intermittently received an infusion of nitroprusside for hypertension and received infusions of norepinephrine and vasopressin during episodes of hypotension.

On the third hospital day, transesophageal echocardiography revealed slight improvement in global ventricular function. Extracorporeal life support was discontinued, and milrinone therapy was continued. While the patient was in the operating room for decannulation of extracorporeal life support and removal of the ventricular assist device, a left ventricular endomyocardial biopsy was performed.

Figure 2.

Endomyocardial-Biopsy Specimens.
Dr. James R. Stone: The biopsy specimen was evaluated with the use of routine, special, and immunohistochemical stains.2 Examination of the specimen revealed acute and healing myocardial injury (Figure 2). There were focal necrotic myocytes, which were C4d+ on immunohistochemical staining. There was a reparative inflammatory infiltrate that was composed primarily of CD68+ macrophages, with rare CD3+ T lymphocytes. There was focal fibrosis, which suggested that the disorder had been present for at least 4 weeks. The cardiomyocytes showed hypertrophy, a nonspecific phenomenon that is consistent with an injury response.3,4 There were no histologic features of active myocarditis or features of a storage or deposition disorder. The differential diagnosis for the myocardial injury includes ischemia, myocardial toxicity, mechanical stress, and treated myocarditis.3,5

Dr. Roy: The next day, marked hypertension developed, and intravenous hydralazine was administered. The blood pressure remained very labile during the next 4 days; therefore, intermittent infusions of sodium nitroprusside and therapy with carvedilol, oral hydralazine, and clonidine were administered. The patient continued to receive renal-replacement therapy, but spontaneous urine output resumed. Blood tests for antinuclear antibodies and antibodies to adenovirus, coxsackievirus, and parvovirus were negative, as was a test for adenovirus DNA. Serum protein electrophoresis revealed low levels of IgG and IgA. Cultures of the blood and urine were sterile. On the seventh hospital day, the blood pressure stabilized and cardiac MRI could be performed.

Dr. Shah: Cardiac MRI, performed without the administration of gadolinium, revealed a mildly reduced left ventricular ejection fraction of 49% and left ventricular mid-to-apical hypokinesis, with relative sparing of the base (see Video 2). Right ventricular function was normal. T2-weighted imaging did not reveal any clear evidence of clinically significant myocardial edema. Because gadolinium was not administered, patterns suggestive of myocarditis or a myocardial scar could not be detected. Given the normal results of coronary angiography and the low level of suspicion for an acute coronary syndrome, the findings in this patient would be consistent with takotsubo (stress) cardiomyopathy.

Dr. Roy: A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:      A 55-year-old woman was transferred to this hospital for evaluation and treatment of cardiogenic shock.

Approximately 4 months before presentation, the patient was admitted to a hospital in her home state for “pounding” in her chest, nausea, and diaphoresis that persisted for 40 minutes after a routine jog. The heart rate was 65 beats per minute, and the blood pressure 138/72 mm Hg; the remainder of the examination was normal. Four serial electrocardiograms were reportedly normal, but the troponin I level was elevated, at 0.055 ng per milliliter, and 11 hours later, it had risen to 0.415 ng per milliliter (normal range, 0 to 0.045). Transthoracic echocardiography revealed normal biventricular function. Coronary angiography revealed no evidence of obstructive coronary artery disease; the left ventricular end-diastolic pressure was 5 mm Hg. After discharge (4 days after admission), cardiac magnetic resonance imaging (MRI) revealed normal biventricular function and size, with no evidence of myocardial edema or fibrosis. Aspirin and a beta blocker were prescribed for presumed exercise-related supraventricular tachycardia.

The symptoms did not recur, and the patient returned to jogging and stopped taking the beta blocker. On the day before her transfer to this hospital, she was on a downhill-skiing trip in Vermont. In the morning, she felt fatigued. In the afternoon, palpitations, dyspnea, and weakness developed while she was at the top of a mountain; the ski patrol took her down the mountain, and the symptoms abated. In the evening, while she was at dinner, she had acute nausea and emesis followed by chest pain and dyspnea. She was taken to a local emergency department. The heart rate was 111 beats per minute, the blood pressure 115/81 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 84% while she was breathing ambient air. Auscultation revealed diffuse crackles in the lungs. The troponin I level was 11.000 ng per milliliter (normal range, 0 to 0.045), the N-terminal pro–B-type natriuretic peptide (NT-proBNP) level 15,159 pg per milliliter (normal range, 0 to 125), the lactate level 4.6 mmol per liter (41.0 mg per deciliter; normal range, 0.5 to 2.0 mmol per liter [4.5 to 18.0 mg per deciliter]), the venous blood pH 7.22 (normal range, 7.38 to 7.46), and the white-cell count 36,100 per cubic millimeter (normal range, 4500 to 11,000). Bedside cardiac ultrasonography revealed severe left ventricular dysfunction with apical ballooning. Intravenous infusions of heparin and furosemide were administered, and the patient was transferred by helicopter to a nearby tertiary care center for treatment of suspected cardiogenic shock.

On the patient’s arrival at the tertiary care center, the temperature was 37.2°C, the heart rate 143 beats per minute, the blood pressure 96/72 mm Hg, the respiratory rate 26 breaths per minute, and the oxygen saturation 84% while she was breathing ambient air and 88 to 94% while she was receiving oxygen through a nonrebreather face mask. On physical examination, she appeared fatigued and had jugular venous distention, diffuse crackles in the lungs, and cold arms and legs. The troponin I level was 4.790 ng per milliliter (normal range, <0.034), the white-cell count 30,240 per cubic millimeter (normal range, 4500 to 11,000), the arterial blood pH 7.08 (normal range, 7.35 to 7.45), the lactate level 5.9 mmol per liter (53 mg per deciliter; normal range, <2.0 mmol per liter [<18 mg per deciliter]), the NT-proBNP level 24,900 pg per milliliter (normal range, <300), and the creatinine level 1.41 mg per deciliter (125 _mol per liter; normal range for women, 0.52 to 1.04 mg per deciliter [46 to 92 _mol per liter]).

Chest radiography revealed diffuse pulmonary edema. Electrocardiography showed sinus tachycardia and T-wave inversions in leads V4 through V6. The trachea was intubated, and mechanical ventilation was initiated for respiratory failure. Transthoracic echocardiography revealed a left ventricular ejection fraction of 15% and left ventricular apical akinesis, as well as severe right ventricular apical dysfunction. Infusions of norepinephrine, dobutamine, epinephrine, amiodarone, propofol, midazolam, fentanyl, and sodium bicarbonate were administered. Empirical methylprednisolone was administered for presumed myocarditis. Coronary angiography revealed normal coronary arteries; the left ventricular end-diastolic pressure was 38 mm Hg. A percutaneous transaortic left ventricular assist device was placed. After the institution of mechanical circulatory support, the intravenous doses of norepinephrine, dobutamine, and epinephrine were tapered and eventually stopped. Hematuria developed, and the urine output declined. The blood pressure was labile, ranging from 60/40 to 140/110 mm Hg, and an infusion of sodium nitroprusside was administered for control of elevated blood pressure. The patient was transferred by helicopter to this hospital.

On the patient’s arrival at this hospital, additional history was obtained from her husband. She had a history of thyroid cancer (unknown pathologic subtype) that had been treated with thyroidectomy and radioactive iodine ablation. Medications included levothyroxine and a calcium supplement. The use of cefadroxil had caused the Stevens–Johnson syndrome. She did not smoke cigarettes, drink alcohol, or use illicit drugs. She was employed in health care, was married, and had one healthy daughter. Her maternal grandfather had died from myocardial infarction at 60 years of age, her father had had an aortic-valve replacement, and her mother had had lung cancer.

On examination, the temperature was 36.9°C, the heart rate 132 beats per minute, the blood pressure 105/72 mm Hg, and the oxygen saturation 96% while the patient was receiving oxygen through a mechanical ventilator (positive end-expiratory pressure, 12; tidal volume, 400 ml; fraction of inspired oxygen, 1.0; respiratory rate, 16 breaths per minute). The pupils were reactive to light in a symmetric but slightly sluggish manner. The patient was able to follow simple commands. She had no masses in the neck or exophthalmos. The jugular veins appeared distended. Auscultation of the chest revealed the hum of the ventricular assist device, distant tachycardic heart sounds, and scattered crackles in the lungs. The ventricular assist device had been secured in place by way of the left groin. She had 1+ pedal edema bilaterally and no rash or lymphadenopathy. A small amount of reddish brown urine was noted.

Table 1.

Laboratory Data.
Levels of thyrotropin, bilirubin, and alkaline phosphatase were normal; other test results are shown in Table 1. Urinalysis revealed 3+ blood. Tests of a nasopharyngeal swab for nucleic acids of influenza A and B and respiratory syncytial virus and for metapneumovirus antigens were negative, as was combination testing for antibodies to human immunodeficiency virus types 1 and 2 and p24 antigen.

Figure 1.

Electrocardiogram.
Dr. Ravi V. Shah: Electrocardiography showed sinus tachycardia, poor R-wave progression, T-wave inversions in leads V3 through V6 and in inferior leads, low QRS voltage, and a prolonged corrected QT (QTc) interval (Figure 1). Chest radiography revealed diffuse interstitial infiltrates, small bilateral pleural effusions, and the tip of the ventricular assist device projecting over the left ventricle. Transthoracic echocardiography revealed severe left ventricular systolic dysfunction, with an estimated ejection fraction of 20% and severe mid-to-apical hypokinesis, as well as right ventricular free-wall and apical dysfunction, no clinically significant valvular disease, and a small pericardial effusion (see Video 1, available with the full text of this article at NEJM.org). On echocardiography, the tip of the ventricular assist device was in the appropriate position in the left ventricle.

Dr. Roy: Shortly after the patient’s arrival at this hospital, hypotension again developed, and infusions of milrinone, epinephrine, and norepinephrine were administered. Femoral venoarterial extracorporeal life support was initiated to facilitate sufficient cardiac output, since the percutaneous ventricular assist device had provided insufficient support and caused increasing hemolysis.1 Continuous venovenous hemofiltration was initiated for anuria, fluid overload, and acidosis in the context of acute kidney injury. Methylprednisolone was administered intravenously.

During the first 3 hospital days, the blood pressure remained labile, with the systolic blood pressure ranging from 65 to 205 mm Hg, despite stable levels of sedation and extracorporeal life support. The patient intermittently received an infusion of nitroprusside for hypertension and received infusions of norepinephrine and vasopressin during episodes of hypotension.

On the third hospital day, transesophageal echocardiography revealed slight improvement in global ventricular function. Extracorporeal life support was discontinued, and milrinone therapy was continued. While the patient was in the operating room for decannulation of extracorporeal life support and removal of the ventricular assist device, a left ventricular endomyocardial biopsy was performed.

Figure 2.

Endomyocardial-Biopsy Specimens.
Dr. James R. Stone: The biopsy specimen was evaluated with the use of routine, special, and immunohistochemical stains.2 Examination of the specimen revealed acute and healing myocardial injury (Figure 2). There were focal necrotic myocytes, which were C4d+ on immunohistochemical staining. There was a reparative inflammatory infiltrate that was composed primarily of CD68+ macrophages, with rare CD3+ T lymphocytes. There was focal fibrosis, which suggested that the disorder had been present for at least 4 weeks. The cardiomyocytes showed hypertrophy, a nonspecific phenomenon that is consistent with an injury response.3,4 There were no histologic features of active myocarditis or features of a storage or deposition disorder. The differential diagnosis for the myocardial injury includes ischemia, myocardial toxicity, mechanical stress, and treated myocarditis.3,5

Dr. Roy: The next day, marked hypertension developed, and intravenous hydralazine was administered. The blood pressure remained very labile during the next 4 days; therefore, intermittent infusions of sodium nitroprusside and therapy with carvedilol, oral hydralazine, and clonidine were administered. The patient continued to receive renal-replacement therapy, but spontaneous urine output resumed. Blood tests for antinuclear antibodies and antibodies to adenovirus, coxsackievirus, and parvovirus were negative, as was a test for adenovirus DNA. Serum protein electrophoresis revealed low levels of IgG and IgA. Cultures of the blood and urine were sterile. On the seventh hospital day, the blood pressure stabilized and cardiac MRI could be performed.

Dr. Shah: Cardiac MRI, performed without the administration of gadolinium, revealed a mildly reduced left ventricular ejection fraction of 49% and left ventricular mid-to-apical hypokinesis, with relative sparing of the base (see Video 2). Right ventricular function was normal. T2-weighted imaging did not reveal any clear evidence of clinically significant myocardial edema. Because gadolinium was not administered, patterns suggestive of myocarditis or a myocardial scar could not be detected. Given the normal results of coronary angiography and the low level of suspicion for an acute coronary syndrome, the findings in this patient would be consistent with takotsubo (stress) cardiomyopathy.

Dr. Roy: A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Takotsubo cardiomyopathy. The patient's symptoms of chest pain, nausea, and diaphoresis, along with elevated troponin levels and severe left ventricular dysfunction with apical ballooning, are consistent with this condition. The absence of obstructive coronary artery disease on angiography and the transient nature of the ventricular dysfunction further support this diagnosis. Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is often triggered by physical or emotional stress and is characterized by transient left ventricular dysfunction.""
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        ""content"": ""The patient is a 55-year-old woman presenting with cardiogenic shock. She has a history of thyroid cancer and has experienced episodes of chest discomfort, nausea, and diaphoresis after physical exertion. Her symptoms are suggestive of a cardiac event, and her elevated troponin I levels support this. However, her coronary angiography is normal, which rules out obstructive coronary artery disease. Her echocardiography reveals severe left ventricular dysfunction with apical ballooning, which is a characteristic feature of Takotsubo cardiomyopathy. This condition, also known as stress cardiomyopathy or \""broken heart syndrome,\"" is typically triggered by severe stress and results in a temporary weakening of the heart muscle. The patient's symptoms, the absence of coronary artery disease, and the echocardiographic findings all point towards this diagnosis. \n\nDiagnosis: Takotsubo cardiomyopathy.""
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10.1056/NEJMcpc1712226,Case 7-2018: A 25-Year-Old Man with New-Onset Seizures,,Homocystinuria due to genetic mutations of the gene encoding cystathionine _-synthase (CBS),Homocystinuria,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:       A 25-year-old man was admitted to this hospital because of new-onset seizures.

The patient had been in his usual state of health until 2 days before admission, when episodes of twitching of the head and neck occurred. The first episode occurred after he awoke in the morning, and the second occurred 2 hours later; each of these episodes lasted approximately 1 minute. A third episode occurred 4 hours after he awoke, lasted 2 minutes, and was accompanied by stiffness of the left arm and left leg; the patient was aware of the twitching and stiffness but did not recall the subsequent events. Observers report that the patient’s full body shook and that he lost consciousness and fell, striking his face. He stopped shaking after a few minutes and regained consciousness, but he was confused and was taken by emergency medical services to another hospital for evaluation. At the other hospital, another self-limited episode with full-body shaking and loss of consciousness reportedly occurred, and levetiracetam was administered. Imaging studies were obtained.

Figure 1.

Imaging Studies of the Head.
Dr. Susie Y. Huang: Computed tomography (CT) of the head, face, and cervical spine, performed without the administration of intravenous contrast material, revealed minimally displaced fractures of the nasal bones bilaterally (Figure 1A) but no acute intracranial process or fractures of the cervical spine. Magnetic resonance imaging (MRI) of the head, performed without the administration of intravenous contrast material, revealed restricted diffusion in the cortex of the right superior frontal gyrus (Figure 1B and 1C). T2-weighted and fluid-attenuated inversion recovery images showed marked hyperintensity in the cortex and white matter of the adjacent right frontal lobe (Figure 1D), a finding consistent with vasogenic edema. Two-dimensional time-of-flight magnetic resonance venography of the head revealed evidence of thrombosis or slow flow in the anterior aspect of the superior sagittal sinus (Figure 1E). Susceptibility-weighted images of the head showed prominent linear hypointensity and evidence of cortical-vein thrombosis (Figure 1F).

Dr. Meltzer: Intravenous unfractionated heparin was administered. The patient was transferred to the neurology inpatient service of this hospital.

On arrival at this hospital, the patient reported no headache, blurred vision, nausea, vomiting, or dizziness. He had no history of bleeding or clotting disorders. Three years before admission, he had been involved in a motor vehicle accident related to falling asleep while driving. A CT scan of the head obtained at that time was reportedly normal, and antiepileptic medications were not prescribed. The patient had a tall stature and long arms; 10 years before admission, he had undergone cardiac evaluation after a family member in the health care field suggested the possibility that he had Marfan’s syndrome. Transthoracic echocardiography performed at that time reportedly showed normal size and function of the right and left ventricles, no clinically significant valvular disease, and a normal aortic root and ascending aorta.

The patient had a history of myopia and had used corrective lenses since he was 15 years of age. Three years before admission, during an ophthalmologic evaluation for laser-assisted refractive surgery, he had received a diagnosis of ectopia lentis with downward lens dislocation in both eyes. The ophthalmologist recommended repeat cardiac evaluation for Marfan’s syndrome, and a transthoracic echocardiogram obtained at that time was again normal. Four years before admission, the patient had undergone cholecystectomy. He had a history of attention deficit–hyperactivity disorder; his mother reported that he had had delays in reaching developmental milestones as a child and had followed an individualized educational plan for a learning disorder. He took no medications. His mother had hypercholesterolemia, his maternal grandmother had dementia and seizures, and his paternal grandfather had died after a stroke when he was 70 years of age. There was no family history of clotting disorders, congenital heart disease, or sudden cardiac death. The patient was a college student, and he did not smoke tobacco or use illicit drugs.

On examination, the temperature was 36.9°C, the blood pressure 112/80 mg Hg, the pulse 55 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The height was 189 cm, the weight 76 kg, the body-mass index (the weight in kilograms divided by the square of the height in meters) 21, and the arm span 192.5 cm. The distance from the top of the pubic symphysis to the floor was 105 cm while he was in the standing position.

The patient was fully alert and oriented. He had complete fluency, with no paraphasic errors or dysarthria. His concentration and attention were intact. His memory was limited, with intact registration but poor recall. The visual fields were full in response to confrontation. The pupils were equal and reactive to light. There was no ptosis, and extraocular movements were intact, with no nystagmus or saccadic pursuit. On the face, sensations to light touch and temperature were normal. There was no facial asymmetry. The tongue and palate were midline, and the hearing was normal in response to a finger rub.

The patient was able to shrug his shoulders and turn his head. His muscle bulk and tone were normal. He did not have cogwheel rigidity, bradykinesia, pronator drift, fasciculations, myoclonus, or tremor. Throughout the body, strength was full. Proprioception and sensations to light touch, temperature, pinprick, and vibration were intact. Deep-tendon reflexes were normal, and the toes were downgoing bilaterally. Results of finger–nose–finger and heel-to-shin tests were normal. Excoriations and ecchymoses were present on the nasal bridge and forehead. The patient had a high arched palate and slight pectus excavatum, and striae were present on his back. When he wrapped a hand around the contralateral wrist, the top of the thumb covered the entire fingernail of the fifth finger. The remainder of the physical examination was normal.

Table 1.

Laboratory Data.
Blood levels of electrolytes and glucose were normal, as were the results of a urinalysis, urine toxicology screen, and tests of renal and liver function. Other laboratory test results are shown in Table 1. Treatment with intravenous unfractionated heparin was continued.

Dr. Huang: CT angiography of the head was performed after the administration of intravenous contrast material. It revealed a nonocclusive filling defect in the anterior aspect of the superior sagittal sinus, a filling defect in the cortical vein of the right frontal lobe, a punctate filling defect in the left internal jugular vein, and an area of mild hypodensity and swelling in the middle aspect of the right superior frontal gyrus, with no associated hemorrhage.

Dr. Meltzer: A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:        A 25-year-old man was admitted to this hospital because of new-onset seizures.

The patient had been in his usual state of health until 2 days before admission, when episodes of twitching of the head and neck occurred. The first episode occurred after he awoke in the morning, and the second occurred 2 hours later; each of these episodes lasted approximately 1 minute. A third episode occurred 4 hours after he awoke, lasted 2 minutes, and was accompanied by stiffness of the left arm and left leg; the patient was aware of the twitching and stiffness but did not recall the subsequent events. Observers report that the patient’s full body shook and that he lost consciousness and fell, striking his face. He stopped shaking after a few minutes and regained consciousness, but he was confused and was taken by emergency medical services to another hospital for evaluation. At the other hospital, another self-limited episode with full-body shaking and loss of consciousness reportedly occurred, and levetiracetam was administered. Imaging studies were obtained.

Figure 1.

Imaging Studies of the Head.
Dr. Susie Y. Huang: Computed tomography (CT) of the head, face, and cervical spine, performed without the administration of intravenous contrast material, revealed minimally displaced fractures of the nasal bones bilaterally (Figure 1A) but no acute intracranial process or fractures of the cervical spine. Magnetic resonance imaging (MRI) of the head, performed without the administration of intravenous contrast material, revealed restricted diffusion in the cortex of the right superior frontal gyrus (Figure 1B and 1C). T2-weighted and fluid-attenuated inversion recovery images showed marked hyperintensity in the cortex and white matter of the adjacent right frontal lobe (Figure 1D), a finding consistent with vasogenic edema. Two-dimensional time-of-flight magnetic resonance venography of the head revealed evidence of thrombosis or slow flow in the anterior aspect of the superior sagittal sinus (Figure 1E). Susceptibility-weighted images of the head showed prominent linear hypointensity and evidence of cortical-vein thrombosis (Figure 1F).

Dr. Meltzer: Intravenous unfractionated heparin was administered. The patient was transferred to the neurology inpatient service of this hospital.

On arrival at this hospital, the patient reported no headache, blurred vision, nausea, vomiting, or dizziness. He had no history of bleeding or clotting disorders. Three years before admission, he had been involved in a motor vehicle accident related to falling asleep while driving. A CT scan of the head obtained at that time was reportedly normal, and antiepileptic medications were not prescribed. The patient had a tall stature and long arms; 10 years before admission, he had undergone cardiac evaluation after a family member in the health care field suggested the possibility that he had Marfan’s syndrome. Transthoracic echocardiography performed at that time reportedly showed normal size and function of the right and left ventricles, no clinically significant valvular disease, and a normal aortic root and ascending aorta.

The patient had a history of myopia and had used corrective lenses since he was 15 years of age. Three years before admission, during an ophthalmologic evaluation for laser-assisted refractive surgery, he had received a diagnosis of ectopia lentis with downward lens dislocation in both eyes. The ophthalmologist recommended repeat cardiac evaluation for Marfan’s syndrome, and a transthoracic echocardiogram obtained at that time was again normal. Four years before admission, the patient had undergone cholecystectomy. He had a history of attention deficit–hyperactivity disorder; his mother reported that he had had delays in reaching developmental milestones as a child and had followed an individualized educational plan for a learning disorder. He took no medications. His mother had hypercholesterolemia, his maternal grandmother had dementia and seizures, and his paternal grandfather had died after a stroke when he was 70 years of age. There was no family history of clotting disorders, congenital heart disease, or sudden cardiac death. The patient was a college student, and he did not smoke tobacco or use illicit drugs.

On examination, the temperature was 36.9°C, the blood pressure 112/80 mg Hg, the pulse 55 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The height was 189 cm, the weight 76 kg, the body-mass index (the weight in kilograms divided by the square of the height in meters) 21, and the arm span 192.5 cm. The distance from the top of the pubic symphysis to the floor was 105 cm while he was in the standing position.

The patient was fully alert and oriented. He had complete fluency, with no paraphasic errors or dysarthria. His concentration and attention were intact. His memory was limited, with intact registration but poor recall. The visual fields were full in response to confrontation. The pupils were equal and reactive to light. There was no ptosis, and extraocular movements were intact, with no nystagmus or saccadic pursuit. On the face, sensations to light touch and temperature were normal. There was no facial asymmetry. The tongue and palate were midline, and the hearing was normal in response to a finger rub.

The patient was able to shrug his shoulders and turn his head. His muscle bulk and tone were normal. He did not have cogwheel rigidity, bradykinesia, pronator drift, fasciculations, myoclonus, or tremor. Throughout the body, strength was full. Proprioception and sensations to light touch, temperature, pinprick, and vibration were intact. Deep-tendon reflexes were normal, and the toes were downgoing bilaterally. Results of finger–nose–finger and heel-to-shin tests were normal. Excoriations and ecchymoses were present on the nasal bridge and forehead. The patient had a high arched palate and slight pectus excavatum, and striae were present on his back. When he wrapped a hand around the contralateral wrist, the top of the thumb covered the entire fingernail of the fifth finger. The remainder of the physical examination was normal.

Table 1.

Laboratory Data.
Blood levels of electrolytes and glucose were normal, as were the results of a urinalysis, urine toxicology screen, and tests of renal and liver function. Other laboratory test results are shown in Table 1. Treatment with intravenous unfractionated heparin was continued.

Dr. Huang: CT angiography of the head was performed after the administration of intravenous contrast material. It revealed a nonocclusive filling defect in the anterior aspect of the superior sagittal sinus, a filling defect in the cortical vein of the right frontal lobe, a punctate filling defect in the left internal jugular vein, and an area of mild hypodensity and swelling in the middle aspect of the right superior frontal gyrus, with no associated hemorrhage.

Dr. Meltzer: A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Cerebral Venous Thrombosis (CVT)\n\nThe patient's symptoms of new-onset seizures and twitching of the head and neck, along with the imaging findings of restricted diffusion in the cortex of the right superior frontal gyrus, hyperintensity in the cortex and white matter of the adjacent right frontal lobe, and evidence of thrombosis or slow flow in the anterior aspect of the superior sagittal sinus, all point towards a diagnosis of cerebral venous thrombosis. The patient's tall stature, long arms, history of ectopia lentis, and high arched palate suggest a connective tissue disorder such as Marfan's syndrome, which can predispose to thrombotic events.""
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        ""content"": ""The patient is a 25-year-old male presenting with new-onset seizures. The differential diagnosis for this patient includes epilepsy, brain tumor, stroke, and cerebral venous thrombosis. The patient's history of myopia, ectopia lentis, tall stature, long arms, and high arched palate suggest a connective tissue disorder such as Marfan's syndrome. However, the patient's echocardiograms have been normal, making Marfan's syndrome less likely. The patient's imaging studies reveal restricted diffusion in the cortex of the right superior frontal gyrus, hyperintensity in the cortex and white matter of the adjacent right frontal lobe, and evidence of thrombosis or slow flow in the anterior aspect of the superior sagittal sinus. These findings are consistent with cerebral venous thrombosis. The patient's history of attention deficit-hyperactivity disorder, developmental delays, and learning disorder suggest a possible genetic syndrome. Given the patient's clinical presentation and imaging findings, the most likely diagnosis is cerebral venous thrombosis.\n\nDiagnosis: Cerebral venous thrombosis.""
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10.1056/NEJMcpc1712223,"Case 6-2018: A 35-Year-Old Woman with Headache, Subjective Fever, and Anemia",,Anemia due to parvovirus B19 infection and autoimmune hemolytic anemia.,Transient aplastic crisis due to parvovirus B19 infection and low-grade autoimmune hemolytic anemia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:          A 35-year-old woman with a history of Crohn’s disease was admitted to this hospital with headache, subjective fever, and anemia.

The patient had been in her usual state of health until 1 week before admission, when headache, fatigue, and myalgias developed. During the next 2 days, she felt generally unwell, and the headache did not diminish with the use of acetaminophen. Five days before admission, she felt feverish, but her temperature (measured at home) was 37.8°C. The frequency of bowel movements increased from a baseline of one to three movements per day to five to eight per day; the color of the stool remained brown, but the consistency became looser, and the stool occasionally contained small amounts of mucus and blood.

Two days before admission, the patient presented to her primary care physician for evaluation. The hemoglobin level was reportedly 8 g per deciliter (reference range, 12 to 16); 6 weeks earlier, the level had been 13 g per deciliter. A provisional diagnosis of a flare of Crohn’s disease was made, and prednisone and intravenous fluids were administered. One day before admission, the hemoglobin level was reportedly 7 g per deciliter, and the patient was asked by her gastroenterologist to stop taking prednisone and to present to the emergency department of this hospital for evaluation.

In the emergency department, the patient reported ongoing headache, fatigue, and myalgias but no dyspnea on exertion or palpitations. She had a history of infertility, and 4 weeks before admission, she had completed one cycle of intrauterine insemination after the administration of follicle-stimulating hormone. She did not become pregnant, and the last menstrual period began 2 weeks before admission, with menstrual flow that was heavier and of longer duration than the flow of previous menstrual cycles.

The patient had received a diagnosis of Crohn’s disease 9 years before admission. Two years later, cytomegalovirus colitis developed while she was receiving infliximab and azathioprine, and her treatment was changed to infliximab monotherapy. Two years before admission, she had evidence of persistent inflammation on endoscopy, and her treatment was then changed to vedolizumab. Eight weeks before admission, the frequency of the vedolizumab dose was increased after the stool calprotectin level was found to be elevated.

The patient also had a history of primary sclerosing cholangitis with normal hepatic synthetic function, stable diffuse intrahepatic disease, and no evidence of a clear dominant stricture on magnetic resonance cholangiopancreatography performed 3 months before admission. In addition to vedolizumab, medications included cetirizine and a prenatal multivitamin with iron. The patient did not smoke tobacco, drank alcohol rarely, and did not use illicit drugs. She lived in New England, worked as an engineer, and was of Asian Indian descent. Her 3-year-old son attended day care regularly. Ten days before admission, fever and an erythematous facial rash had developed in the son; he was not evaluated by a medical provider and recovered after 2 days.

On examination, the temperature was 36.7°C, the blood pressure 103/66 mm Hg, the pulse 96 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She was alert and oriented. The sclerae were anicteric, and the conjunctivae were pale. The oropharynx appeared normal, and there was no cervical lymphadenopathy. She did not have a rash, petechiae, ecchymoses, spider angiomas, or palmar erythema. Bowel sounds were present, and the abdomen was soft, nondistended, and nontender on palpation; there was no splenomegaly. The first and second heart sounds were normal, without murmurs. The arms and legs did not have edema. A rectal examination revealed brown stool that tested positive for fecal occult blood.

Table 1.

Laboratory Data.
Blood levels of electrolytes, glucose, total protein, albumin, folate, vitamin B12, and fibrinogen were normal, as were results of kidney-function and coagulation tests. The total bilirubin level was 1.1 mg per deciliter (19 _mol per liter; reference range, 0 to 1.0 mg per deciliter [0 to 17 _mol per liter]); it had increased from a baseline level of 0.3 to 0.7 mg per deciliter (5 to 12 _mol per liter). Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2 were negative. Urinalysis revealed a specific gravity of 1.003 (reference range, 1.001 to 1.035) and a pH of 6 (reference range, 5 to 9) and was negative for glucose, blood, protein, bilirubin, and urobilinogen. Other laboratory test results are shown in Table 1.

Examination of a peripheral-blood smear revealed sparse red cells, which were normal in size and central pallor, with scattered spherocytes; there were no schistocytes or reticulocytes. White cells and platelets appeared normal, except for the presence of a few atypical lymphocytes. One unit of packed red cells was transfused, and the patient was admitted to this hospital. Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:      A 35-year-old woman with a history of Crohn’s disease was admitted to this hospital with headache, subjective fever, and anemia.

The patient had been in her usual state of health until 1 week before admission, when headache, fatigue, and myalgias developed. During the next 2 days, she felt generally unwell, and the headache did not diminish with the use of acetaminophen. Five days before admission, she felt feverish, but her temperature (measured at home) was 37.8°C. The frequency of bowel movements increased from a baseline of one to three movements per day to five to eight per day; the color of the stool remained brown, but the consistency became looser, and the stool occasionally contained small amounts of mucus and blood.

Two days before admission, the patient presented to her primary care physician for evaluation. The hemoglobin level was reportedly 8 g per deciliter (reference range, 12 to 16); 6 weeks earlier, the level had been 13 g per deciliter. A provisional diagnosis of a flare of Crohn’s disease was made, and prednisone and intravenous fluids were administered. One day before admission, the hemoglobin level was reportedly 7 g per deciliter, and the patient was asked by her gastroenterologist to stop taking prednisone and to present to the emergency department of this hospital for evaluation.

In the emergency department, the patient reported ongoing headache, fatigue, and myalgias but no dyspnea on exertion or palpitations. She had a history of infertility, and 4 weeks before admission, she had completed one cycle of intrauterine insemination after the administration of follicle-stimulating hormone. She did not become pregnant, and the last menstrual period began 2 weeks before admission, with menstrual flow that was heavier and of longer duration than the flow of previous menstrual cycles.

The patient had received a diagnosis of Crohn’s disease 9 years before admission. Two years later, cytomegalovirus colitis developed while she was receiving infliximab and azathioprine, and her treatment was changed to infliximab monotherapy. Two years before admission, she had evidence of persistent inflammation on endoscopy, and her treatment was then changed to vedolizumab. Eight weeks before admission, the frequency of the vedolizumab dose was increased after the stool calprotectin level was found to be elevated.

The patient also had a history of primary sclerosing cholangitis with normal hepatic synthetic function, stable diffuse intrahepatic disease, and no evidence of a clear dominant stricture on magnetic resonance cholangiopancreatography performed 3 months before admission. In addition to vedolizumab, medications included cetirizine and a prenatal multivitamin with iron. The patient did not smoke tobacco, drank alcohol rarely, and did not use illicit drugs. She lived in New England, worked as an engineer, and was of Asian Indian descent. Her 3-year-old son attended day care regularly. Ten days before admission, fever and an erythematous facial rash had developed in the son; he was not evaluated by a medical provider and recovered after 2 days.

On examination, the temperature was 36.7°C, the blood pressure 103/66 mm Hg, the pulse 96 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She was alert and oriented. The sclerae were anicteric, and the conjunctivae were pale. The oropharynx appeared normal, and there was no cervical lymphadenopathy. She did not have a rash, petechiae, ecchymoses, spider angiomas, or palmar erythema. Bowel sounds were present, and the abdomen was soft, nondistended, and nontender on palpation; there was no splenomegaly. The first and second heart sounds were normal, without murmurs. The arms and legs did not have edema. A rectal examination revealed brown stool that tested positive for fecal occult blood.

Table 1.

Laboratory Data.
Blood levels of electrolytes, glucose, total protein, albumin, folate, vitamin B12, and fibrinogen were normal, as were results of kidney-function and coagulation tests. The total bilirubin level was 1.1 mg per deciliter (19 _mol per liter; reference range, 0 to 1.0 mg per deciliter [0 to 17 _mol per liter]); it had increased from a baseline level of 0.3 to 0.7 mg per deciliter (5 to 12 _mol per liter). Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2 were negative. Urinalysis revealed a specific gravity of 1.003 (reference range, 1.001 to 1.035) and a pH of 6 (reference range, 5 to 9) and was negative for glucose, blood, protein, bilirubin, and urobilinogen. Other laboratory test results are shown in Table 1.

Examination of a peripheral-blood smear revealed sparse red cells, which were normal in size and central pallor, with scattered spherocytes; there were no schistocytes or reticulocytes. White cells and platelets appeared normal, except for the presence of a few atypical lymphocytes. One unit of packed red cells was transfused, and the patient was admitted to this hospital. Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Parvovirus B19 infection. The patient's symptoms of headache, fatigue, myalgias, and anemia, along with her son's recent illness featuring fever and a facial rash, suggest a viral infection. Parvovirus B19 is known to cause these symptoms and is common in children. The patient's anemia and lack of reticulocytes on the peripheral blood smear are consistent with parvovirus B19, which causes a temporary halt in red blood cell production leading to severe anemia. This is particularly likely in this patient due to her history of Crohn's disease and primary sclerosing cholangitis, both of which can cause anemia.""
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        ""content"": ""The patient's symptoms of headache, fatigue, myalgias, and anemia, along with her history of Crohn's disease and primary sclerosing cholangitis, suggest an autoimmune or inflammatory condition. The sudden drop in hemoglobin levels and the presence of spherocytes on the peripheral blood smear suggest hemolytic anemia. The absence of schistocytes rules out microangiopathic hemolytic anemia. The absence of reticulocytes, which should be increased in response to hemolysis, suggests that the bone marrow is not responding appropriately, indicating either a marrow failure syndrome or an aplastic crisis. The patient's son's recent illness with fever and rash suggests a viral infection, which can cause an aplastic crisis in patients with chronic hemolytic anemias. The patient's history of Crohn's disease and primary sclerosing cholangitis, both of which are associated with autoimmune conditions, raises the possibility of an autoimmune hemolytic anemia. However, the direct antiglobulin test (DAT, or Coombs test) is negative, which makes autoimmune hemolytic anemia less likely. The patient's history of recent infertility treatment with follicle-stimulating hormone suggests a possible exposure to Parvovirus B19, which is known to cause aplastic crisis and is often associated with exposure to young children, as in a daycare setting. \n\nDiagnosis: Aplastic crisis, likely secondary to Parvovirus B19 infection.""
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        ""content"": ""The patient is a 35-year-old woman with a history of Crohn's disease and primary sclerosing cholangitis who presents with headache, subjective fever, and anemia. The differential diagnosis for this patient includes a flare of Crohn's disease, infection, malignancy, and autoimmune hemolytic anemia. The patient's symptoms of increased frequency of bowel movements, fatigue, and myalgias could be consistent with a flare of Crohn's disease. However, the patient's hemoglobin level dropped significantly from 13 g/dL to 7 g/dL within a span of 6 weeks, which is not typically seen in a Crohn's flare. Infection could also cause the patient's symptoms, but the patient does not have a fever and her white blood cell count is normal, making infection less likely. Malignancy could cause anemia, but the patient does not have any other symptoms suggestive of malignancy such as weight loss or night sweats. The patient's peripheral blood smear shows sparse red cells with scattered spherocytes and no reticulocytes, which is suggestive of autoimmune hemolytic anemia. This condition can occur in patients with autoimmune diseases, which the patient has a history of. Therefore, the most likely diagnosis is autoimmune hemolytic anemia.\n\nDiagnosis: Autoimmune hemolytic anemia.""
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10.1056/NEJMcpc1707556,Case 5-2018: A 63-Year-Old Man with Confusion after Stem-Cell Transplantation,,"Human herpesvirus 6–related meningoencephalitis.

Human herpesvirus 6–related myocarditis and interstitial nephritis.",Human herpesvirus 6–related encephalitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:           A 63-year-old man was admitted to this hospital with confusion and weakness 5 months after he had undergone allogeneic stem-cell transplantation for chronic lymphocytic leukemia (CLL).

The patient had been generally well until 2 years before this admission, when routine tests performed at another hospital revealed a white-cell count of 57,000 per cubic millimeter. A diagnosis of CLL with chromosome 17p deletion was made. Approximately 21 months before this admission, the patient was seen by an oncologist at a second hospital, and he was referred to the Cancer Center of this hospital. Shortly thereafter, chest pain and dyspnea occurred. A diagnosis of pulmonary embolism was made, and warfarin therapy was begun. Two weeks later, on evaluation in the Cancer Center, warfarin therapy was stopped and treatment with ibrutinib and enoxaparin was begun.

Five months before this admission, the patient underwent allogeneic stem-cell transplantation, at this hospital, from a matched, unrelated donor after reduced-intensity conditioning with fludarabine and melphalan. Post-transplantation complications included the engraftment syndrome with respiratory failure (leading to mechanical ventilation), hemolysis caused by ABO incompatibility, paroxysmal atrial fibrillation, acute kidney injury, delirium, and fevers. An evaluation of delirium included magnetic resonance imaging (MRI) of the head and lumbar puncture. The opening pressure was 34 cm of water (normal range, 10 to 20), and cerebrospinal fluid (CSF) analysis revealed a red-cell count of 255 per cubic millimeter, a glucose level of 125 mg per deciliter (6.9 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]), a total protein level of 26 mg per deciliter (reference range, 5 to 55), and a nucleated-cell count of 28 per cubic millimeter (90% lymphocytes). Culture of the CSF was sterile, and nucleic acid testing for herpes simplex virus was negative. The delirium was thought to be related to medications or the engraftment syndrome, and after several days, the mental status improved.

Thirty-eight days before this admission, pathological examination of a bone marrow–biopsy specimen and fluorescence in situ hybridization testing showed evidence of trilineage hematopoiesis and residual CLL. Thirty-five days before this admission, fever and abdominal pain developed, and the patient underwent cholecystectomy for acute gangrenous cholecystitis.

Twelve days before the current admission, the patient was admitted to this hospital because of weight loss of 34 kg during the previous 4 months. A chest radiograph showed a left basilar opacity. Examination and culture of biopsy specimens obtained with the use of upper endoscopy and sigmoidoscopy showed no evidence of gastrointestinal graft-versus-host disease (GVHD), candidiasis, or invasive cytomegalovirus (CMV) infection. There was delayed gastric emptying. The patient declined parenteral and percutaneous enteral nutrition, and dronabinol therapy was initiated. During that admission, the patient had episodes of mild confusion, and fever to a temperature of 38.6°C occurred on the fourth hospital day.

Dr. Pamela W. Schaefer: On the fifth hospital day, MRI of the head was performed after the administration of contrast material. Axial fluid-attenuated inversion recovery (FLAIR) images showed subtle hyperintensity in the occipital sulci bilaterally. Gadolinium-enhanced axial T1-weighted images showed subtle enhancement in some of the occipital sulci. These findings could represent a subtle inflammatory, infectious, or neoplastic leptomeningeal process or could be artifactual. On a coronal FLAIR image, the hippocampi appeared normal and there was a nonspecific hyperintense focus in the right corona radiata, a common finding in a patient of this age. The hippocampi also appeared normal on axial T2-weighted images and axial diffusion-weighted images. A sagittal T1-weighted image showed a low signal in the calvarial bone marrow that was most likely due to the known CLL or to a reactive change. There was no evidence of acute ischemia, intracranial hemorrhage, mass lesion, cortical abnormality, or brain swelling.

Dr. Cohen: Empirical ceftazidime, metronidazole, and fluconazole were administered, and mirtazapine therapy was begun. Blood cultures were negative. Urinalysis revealed 1+ protein, 1+ leukocyte esterase, and 1+ bacteria, and a urine culture grew few Klebsiella pneumoniae. The fevers resolved and the confusion diminished, with some residual forgetfulness and “fogginess.” The patient was discharged home on the ninth hospital day.

One day before this admission, the patient reportedly fell and hit his head. He was taken to the emergency department of the second hospital. On evaluation, he was awake, agitated, and confused, with generalized weakness. Haloperidol was administered. The patient was transferred to the oncology unit of this hospital.

The patient had a history of treated hepatitis C virus infection, hypertension, and migraines. Medications were ibrutinib, famciclovir, sirolimus, tacrolimus, trimethoprim–sulfamethoxazole, dronabinol, mirtazapine, olanzapine, ursodiol, nystatin suspension, omeprazole, cholecalciferol, and zinc acetate, as well as lorazepam as needed. He had no known allergies to medications. He lived with his longtime partner and worked in the entertainment industry. He had a 45-pack-year history of cigarette smoking and had quit 5 months earlier; he had previously stopped drinking alcohol after a period of heavy use of unknown duration, and he had used intranasal cocaine in the remote past. His family history was notable for breast cancer in his mother and liver cancer in his brother. He had one healthy adult child.

On examination, the temperature was 37.4°C, the pulse 102 beats per minute, the blood pressure 142/79 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. He had cachexia, appeared fatigued, and was oriented to person but not to place or time. He could not name the president of the United States or the days of the week, and he had difficulty following commands. He made inappropriate comments, reported visual hallucinations (including “smoke coming out of the doctor’s nose”), and picked at the bedsheets. The mucous membranes were dry. There was a small amount of dried blood above his left eye and outer left ear. An ejection murmur was heard in the precordium. An intention tremor was present in each arm. Asterixis was absent. Strength was 4+/5 in both arms and 4/5 in both legs. The remainder of the general and neurologic examinations, including examination of the function of cranial nerves II through XII, was normal.

Table 1.

Laboratory Data.
Blood levels of thyrotropin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, creatine kinase, and vitamin B12 were normal, as was the serum osmolality; other test results are shown in Table 1. Urinalysis revealed clear urine, with no nitrite or leukocyte esterase, 0 to 2 white cells per high-power field, and 1+ bacteria. Urine and blood samples were obtained for culture, and additional imaging studies were performed.

Dr. Schaefer: A chest radiograph showed clear lungs. Sagittal, axial, and coronal images from computed tomography (CT) of the head, performed without the administration of contrast material, showed no evidence of brain swelling, edema, ischemia, hemorrhage, or other acute intracranial abnormalities.

Dr. Cohen: Electroencephalography showed diffuse slowing of the theta waveform frequency, predominantly in the frontal area, but no epileptiform discharges. On the second hospital day, an attempt to perform a lumbar puncture was unsuccessful because the patient was not able to follow commands. On the third hospital day, a lumbar puncture was successfully performed and revealed an opening pressure of 17 cm of water; results of CSF analysis are shown in Table 1.

Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:            A 63-year-old man was admitted to this hospital with confusion and weakness 5 months after he had undergone allogeneic stem-cell transplantation for chronic lymphocytic leukemia (CLL).

The patient had been generally well until 2 years before this admission, when routine tests performed at another hospital revealed a white-cell count of 57,000 per cubic millimeter. A diagnosis of CLL with chromosome 17p deletion was made. Approximately 21 months before this admission, the patient was seen by an oncologist at a second hospital, and he was referred to the Cancer Center of this hospital. Shortly thereafter, chest pain and dyspnea occurred. A diagnosis of pulmonary embolism was made, and warfarin therapy was begun. Two weeks later, on evaluation in the Cancer Center, warfarin therapy was stopped and treatment with ibrutinib and enoxaparin was begun.

Five months before this admission, the patient underwent allogeneic stem-cell transplantation, at this hospital, from a matched, unrelated donor after reduced-intensity conditioning with fludarabine and melphalan. Post-transplantation complications included the engraftment syndrome with respiratory failure (leading to mechanical ventilation), hemolysis caused by ABO incompatibility, paroxysmal atrial fibrillation, acute kidney injury, delirium, and fevers. An evaluation of delirium included magnetic resonance imaging (MRI) of the head and lumbar puncture. The opening pressure was 34 cm of water (normal range, 10 to 20), and cerebrospinal fluid (CSF) analysis revealed a red-cell count of 255 per cubic millimeter, a glucose level of 125 mg per deciliter (6.9 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]), a total protein level of 26 mg per deciliter (reference range, 5 to 55), and a nucleated-cell count of 28 per cubic millimeter (90% lymphocytes). Culture of the CSF was sterile, and nucleic acid testing for herpes simplex virus was negative. The delirium was thought to be related to medications or the engraftment syndrome, and after several days, the mental status improved.

Thirty-eight days before this admission, pathological examination of a bone marrow–biopsy specimen and fluorescence in situ hybridization testing showed evidence of trilineage hematopoiesis and residual CLL. Thirty-five days before this admission, fever and abdominal pain developed, and the patient underwent cholecystectomy for acute gangrenous cholecystitis.

Twelve days before the current admission, the patient was admitted to this hospital because of weight loss of 34 kg during the previous 4 months. A chest radiograph showed a left basilar opacity. Examination and culture of biopsy specimens obtained with the use of upper endoscopy and sigmoidoscopy showed no evidence of gastrointestinal graft-versus-host disease (GVHD), candidiasis, or invasive cytomegalovirus (CMV) infection. There was delayed gastric emptying. The patient declined parenteral and percutaneous enteral nutrition, and dronabinol therapy was initiated. During that admission, the patient had episodes of mild confusion, and fever to a temperature of 38.6°C occurred on the fourth hospital day.

Dr. Pamela W. Schaefer: On the fifth hospital day, MRI of the head was performed after the administration of contrast material. Axial fluid-attenuated inversion recovery (FLAIR) images showed subtle hyperintensity in the occipital sulci bilaterally. Gadolinium-enhanced axial T1-weighted images showed subtle enhancement in some of the occipital sulci. These findings could represent a subtle inflammatory, infectious, or neoplastic leptomeningeal process or could be artifactual. On a coronal FLAIR image, the hippocampi appeared normal and there was a nonspecific hyperintense focus in the right corona radiata, a common finding in a patient of this age. The hippocampi also appeared normal on axial T2-weighted images and axial diffusion-weighted images. A sagittal T1-weighted image showed a low signal in the calvarial bone marrow that was most likely due to the known CLL or to a reactive change. There was no evidence of acute ischemia, intracranial hemorrhage, mass lesion, cortical abnormality, or brain swelling.

Dr. Cohen: Empirical ceftazidime, metronidazole, and fluconazole were administered, and mirtazapine therapy was begun. Blood cultures were negative. Urinalysis revealed 1+ protein, 1+ leukocyte esterase, and 1+ bacteria, and a urine culture grew few Klebsiella pneumoniae. The fevers resolved and the confusion diminished, with some residual forgetfulness and “fogginess.” The patient was discharged home on the ninth hospital day.

One day before this admission, the patient reportedly fell and hit his head. He was taken to the emergency department of the second hospital. On evaluation, he was awake, agitated, and confused, with generalized weakness. Haloperidol was administered. The patient was transferred to the oncology unit of this hospital.

The patient had a history of treated hepatitis C virus infection, hypertension, and migraines. Medications were ibrutinib, famciclovir, sirolimus, tacrolimus, trimethoprim–sulfamethoxazole, dronabinol, mirtazapine, olanzapine, ursodiol, nystatin suspension, omeprazole, cholecalciferol, and zinc acetate, as well as lorazepam as needed. He had no known allergies to medications. He lived with his longtime partner and worked in the entertainment industry. He had a 45-pack-year history of cigarette smoking and had quit 5 months earlier; he had previously stopped drinking alcohol after a period of heavy use of unknown duration, and he had used intranasal cocaine in the remote past. His family history was notable for breast cancer in his mother and liver cancer in his brother. He had one healthy adult child.

On examination, the temperature was 37.4°C, the pulse 102 beats per minute, the blood pressure 142/79 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. He had cachexia, appeared fatigued, and was oriented to person but not to place or time. He could not name the president of the United States or the days of the week, and he had difficulty following commands. He made inappropriate comments, reported visual hallucinations (including “smoke coming out of the doctor’s nose”), and picked at the bedsheets. The mucous membranes were dry. There was a small amount of dried blood above his left eye and outer left ear. An ejection murmur was heard in the precordium. An intention tremor was present in each arm. Asterixis was absent. Strength was 4+/5 in both arms and 4/5 in both legs. The remainder of the general and neurologic examinations, including examination of the function of cranial nerves II through XII, was normal.

Table 1.

Laboratory Data.
Blood levels of thyrotropin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, creatine kinase, and vitamin B12 were normal, as was the serum osmolality; other test results are shown in Table 1. Urinalysis revealed clear urine, with no nitrite or leukocyte esterase, 0 to 2 white cells per high-power field, and 1+ bacteria. Urine and blood samples were obtained for culture, and additional imaging studies were performed.

Dr. Schaefer: A chest radiograph showed clear lungs. Sagittal, axial, and coronal images from computed tomography (CT) of the head, performed without the administration of contrast material, showed no evidence of brain swelling, edema, ischemia, hemorrhage, or other acute intracranial abnormalities.

Dr. Cohen: Electroencephalography showed diffuse slowing of the theta waveform frequency, predominantly in the frontal area, but no epileptiform discharges. On the second hospital day, an attempt to perform a lumbar puncture was unsuccessful because the patient was not able to follow commands. On the third hospital day, a lumbar puncture was successfully performed and revealed an opening pressure of 17 cm of water; results of CSF analysis are shown in Table 1.

Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's history of allogeneic stem-cell transplantation, along with his symptoms of confusion, weakness, and visual hallucinations, suggest a neurological issue. The MRI of the head showed subtle hyperintensity in the occipital sulci bilaterally, which could indicate an inflammatory, infectious, or neoplastic leptomeningeal process. The patient's CSF analysis showed a high protein level and a high nucleated-cell count, which could indicate an infection or inflammation in the central nervous system. The patient's history of CLL and recent stem-cell transplantation also put him at risk for opportunistic infections. The patient's symptoms, along with the MRI and CSF findings, suggest a diagnosis of central nervous system infection or inflammation, possibly due to an opportunistic infection following stem-cell transplantation.\n\nDiagnosis: Central nervous system infection or inflammation due to opportunistic infection post stem-cell transplantation.""
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        ""content"": ""The patient is a 63-year-old man with a history of chronic lymphocytic leukemia (CLL) who underwent allogeneic stem-cell transplantation. He presents with confusion and weakness. The differential diagnosis for this patient includes central nervous system (CNS) infection, CNS lymphoma, medication side effects, metabolic encephalopathy, and graft-versus-host disease (GVHD). The patient's history of stem-cell transplantation and immunosuppressive therapy puts him at risk for CNS infections, including bacterial, viral, and fungal infections. However, his cerebrospinal fluid (CSF) analysis does not show a significant increase in white blood cells, which would be expected in an infection. CNS lymphoma could also present with these symptoms, but the patient's MRI does not show any mass lesions. The patient is on multiple medications, including ibrutinib, famciclovir, sirolimus, tacrolimus, and others, which could potentially cause confusion and weakness as side effects. However, the patient's symptoms are quite severe and he does not have other side effects that are commonly associated with these medications. Metabolic encephalopathy could also cause confusion and weakness, but the patient's lab results do not show any significant metabolic abnormalities. Finally, GVHD could potentially cause these symptoms if it involves the CNS. The patient's history of stem-cell transplantation and the lack of other explanations for his symptoms make this a likely diagnosis.\n\nDiagnosis: Central nervous system graft-versus-host disease.""
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}",Central nervous system graft-versus-host disease,N
10.1056/NEJMcpc1706110,"Case 4-2018: A Newborn with Thrombocytopenia, Cataracts, and Hepatosplenomegaly",,Congenital rubella syndrome.,Congenital rubella syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:             A newborn boy was transferred to the neonatal intensive care unit (ICU) of this hospital because of thrombocytopenia and abnormal results on an eye examination for red reflex and on a hearing screening.

The patient was born to a 27-year-old mother (gravida 2, para 2) by spontaneous vaginal delivery at another hospital after an uncomplicated gestation of 39 weeks 4 days. His mother had received prenatal care in Nigeria and had also been seen by an obstetrician in New England for one office visit at 24 weeks 4 days of gestation. At that appointment, results of an ultrasonographic survey of the fetal anatomy were normal, and antepartum screening tests for human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and syphilis were negative. A maternal test for IgG antibodies to rubella virus was positive (>500 IU per milliliter; reference range for immunity, ≥9.9), as was a test for IgG antibodies to varicella–zoster virus. The maternal ABO blood type was O, Rh positive, and screening for antibodies to red cells was negative; hemoglobin electrophoresis revealed the presence of hemoglobin AS.

The mother traveled back to Nigeria before returning to New England at 34 weeks of gestation in anticipation of the birth. At delivery, meconium was present. The 1-minute and 5-minute Apgar scores were 7 and 8, respectively. The birth weight was 3.21 kg (54th percentile), the length 51 cm (72nd percentile), and the head circumference 33.5 cm (22nd percentile). The newborn had tremulous movements of the arms and legs, and the blood glucose level was reportedly 20 mg per deciliter (1.1 mmol per liter). He was admitted to the special care nursery at the other hospital, where intravenous fluids that contained dextrose were administered and breast-feeding was initiated; the blood glucose level normalized.

On examination of the newborn the following day, the vital signs were normal. Scattered petechiae were present on the face, and an eye examination revealed that the red reflex was absent in the left eye and decreased in the right eye. The platelet count was 18,000 per cubic millimeter (reference range, 150,000 to 450,000). Newborn blood-spot screening tests (a panel of tests for multiple congenital diseases, primarily inborn errors of metabolism) revealed the presence of hemoglobin FAS and were otherwise negative. On a hearing screening, no auditory brain-stem response was detected when the test sound was presented to either ear. A polymerase-chain-reaction (PCR) assay for cytomegalovirus DNA in the urine was negative, as was a maternal rapid plasma reagin test. At 48 hours of age, the patient was transferred to the neonatal ICU of this hospital for further evaluation and treatment.

The history was obtained from the patient’s mother. She reported that she was unsure whether the newborn responded to her voice or other sounds. She had received treatment for malaria during the first trimester of pregnancy and had received amoxicillin–clavulanate for a respiratory tract infection during the early part of the third trimester. The family lived in an urban area of Nigeria, where the parents worked in the banking sector and employed a live-in nanny to help care for the patient’s 3-year-old sister. They did not have pets and had not noted rodents or other pests in their home. The patient’s mother, father, and sister were healthy. During the mother’s previous pregnancy, prenatal care had taken place exclusively in Nigeria; the child had been delivered in the southeastern United States, and the mother and child had traveled back to Nigeria shortly after the birth. Otherwise, the mother had not traveled internationally; the father had traveled to China for business during the past year.

Table 1.

Laboratory Data.
On examination in the neonatal ICU, the newborn was awake and appeared well, and the vital signs were normal. Scattered petechiae were present on the face. The red reflex was absent in both eyes. A systolic ejection murmur (grade 2/6) was heard in the left upper chest. Mild hepatosplenomegaly was present. Increased muscle tone was present in the arms and legs, and intermittent, suppressible, rapid shaking movements occurred in the arms. The remainder of the examination was normal. The hemoglobin level, hematocrit, red-cell count, red-cell indexes, and blood levels of glucose, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were normal, as were the results of coagulation tests; other laboratory test results are shown in Table 1. A blood sample was obtained for culture. Ampicillin and gentamicin were administered intravenously, and platelets were transfused.

Figure 1.

Cranial Ultrasound Images.
Dr. Katherine Nimkin: Cranial ultrasonography was performed through the anterior fontanelle (Figure 1). Sagittal images showed multiple punctate, echogenic foci in the periventricular white matter bilaterally, a finding consistent with calcifications. Punctate calcifications were also present in the basal ganglia. Complex subependymal cysts were seen in the caudothalamic grooves bilaterally; these were larger on the left side than on the right side. There was mild dilatation of the left lateral ventricle. Linear, branching, echogenic foci were present in the basal ganglia bilaterally, a finding consistent with lenticulostriate vasculopathy.

Intracranial calcifications in the neonate may result from a variety of conditions. Congenital infection is usually the first diagnostic consideration; other causes include hypoxic–ischemic injury, neoplasm, and genetic disorders.1 The pattern of calcification in the periventricular white matter and basal ganglia in this patient is suggestive of congenital infection.2 Subependymal cysts, which were seen in this case, may result from hemorrhage, hypoxic–ischemic injury, or congenital infection.3 These cysts may also result from rare metabolic and genetic disorders and may be seen in healthy newborns. Lenticulostriate vasculopathy is the presence of hyperechogenic vessels in the basal ganglia or thalami on cranial ultrasonography. This finding may be seen in healthy infants; however, it has been associated with infectious and noninfectious conditions and is most likely a nonspecific marker of perinatal brain injury.4

Figure 2.

Chest Radiograph and Abdominal Ultrasound Image.
In this patient, chest radiography (Figure 2A) revealed a normal heart and mediastinum and clear lungs. There were thin, transverse lucent bands in the proximal humeral metaphyses bilaterally. Metaphyseal lucent bands in the neonate may result from changes associated with chronic stress or from congenital infections. Other causes of metaphyseal lucent bands include metastatic neuroblastoma and leukemia. Abdominal ultrasonography confirmed the finding of hepatosplenomegaly (Figure 2B).

Dr. Matthiesen: A slit-lamp examination revealed lamellar cataracts in both eyes, with anterior capsular plaque in the left eye. A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:          A newborn boy was transferred to the neonatal intensive care unit (ICU) of this hospital because of thrombocytopenia and abnormal results on an eye examination for red reflex and on a hearing screening.

The patient was born to a 27-year-old mother (gravida 2, para 2) by spontaneous vaginal delivery at another hospital after an uncomplicated gestation of 39 weeks 4 days. His mother had received prenatal care in Nigeria and had also been seen by an obstetrician in New England for one office visit at 24 weeks 4 days of gestation. At that appointment, results of an ultrasonographic survey of the fetal anatomy were normal, and antepartum screening tests for human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and syphilis were negative. A maternal test for IgG antibodies to rubella virus was positive (>500 IU per milliliter; reference range for immunity, ≥9.9), as was a test for IgG antibodies to varicella–zoster virus. The maternal ABO blood type was O, Rh positive, and screening for antibodies to red cells was negative; hemoglobin electrophoresis revealed the presence of hemoglobin AS.

The mother traveled back to Nigeria before returning to New England at 34 weeks of gestation in anticipation of the birth. At delivery, meconium was present. The 1-minute and 5-minute Apgar scores were 7 and 8, respectively. The birth weight was 3.21 kg (54th percentile), the length 51 cm (72nd percentile), and the head circumference 33.5 cm (22nd percentile). The newborn had tremulous movements of the arms and legs, and the blood glucose level was reportedly 20 mg per deciliter (1.1 mmol per liter). He was admitted to the special care nursery at the other hospital, where intravenous fluids that contained dextrose were administered and breast-feeding was initiated; the blood glucose level normalized.

On examination of the newborn the following day, the vital signs were normal. Scattered petechiae were present on the face, and an eye examination revealed that the red reflex was absent in the left eye and decreased in the right eye. The platelet count was 18,000 per cubic millimeter (reference range, 150,000 to 450,000). Newborn blood-spot screening tests (a panel of tests for multiple congenital diseases, primarily inborn errors of metabolism) revealed the presence of hemoglobin FAS and were otherwise negative. On a hearing screening, no auditory brain-stem response was detected when the test sound was presented to either ear. A polymerase-chain-reaction (PCR) assay for cytomegalovirus DNA in the urine was negative, as was a maternal rapid plasma reagin test. At 48 hours of age, the patient was transferred to the neonatal ICU of this hospital for further evaluation and treatment.

The history was obtained from the patient’s mother. She reported that she was unsure whether the newborn responded to her voice or other sounds. She had received treatment for malaria during the first trimester of pregnancy and had received amoxicillin–clavulanate for a respiratory tract infection during the early part of the third trimester. The family lived in an urban area of Nigeria, where the parents worked in the banking sector and employed a live-in nanny to help care for the patient’s 3-year-old sister. They did not have pets and had not noted rodents or other pests in their home. The patient’s mother, father, and sister were healthy. During the mother’s previous pregnancy, prenatal care had taken place exclusively in Nigeria; the child had been delivered in the southeastern United States, and the mother and child had traveled back to Nigeria shortly after the birth. Otherwise, the mother had not traveled internationally; the father had traveled to China for business during the past year.

Table 1.

Laboratory Data.
On examination in the neonatal ICU, the newborn was awake and appeared well, and the vital signs were normal. Scattered petechiae were present on the face. The red reflex was absent in both eyes. A systolic ejection murmur (grade 2/6) was heard in the left upper chest. Mild hepatosplenomegaly was present. Increased muscle tone was present in the arms and legs, and intermittent, suppressible, rapid shaking movements occurred in the arms. The remainder of the examination was normal. The hemoglobin level, hematocrit, red-cell count, red-cell indexes, and blood levels of glucose, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were normal, as were the results of coagulation tests; other laboratory test results are shown in Table 1. A blood sample was obtained for culture. Ampicillin and gentamicin were administered intravenously, and platelets were transfused.

Figure 1.

Cranial Ultrasound Images.
Dr. Katherine Nimkin: Cranial ultrasonography was performed through the anterior fontanelle (Figure 1). Sagittal images showed multiple punctate, echogenic foci in the periventricular white matter bilaterally, a finding consistent with calcifications. Punctate calcifications were also present in the basal ganglia. Complex subependymal cysts were seen in the caudothalamic grooves bilaterally; these were larger on the left side than on the right side. There was mild dilatation of the left lateral ventricle. Linear, branching, echogenic foci were present in the basal ganglia bilaterally, a finding consistent with lenticulostriate vasculopathy.

Intracranial calcifications in the neonate may result from a variety of conditions. Congenital infection is usually the first diagnostic consideration; other causes include hypoxic–ischemic injury, neoplasm, and genetic disorders.1 The pattern of calcification in the periventricular white matter and basal ganglia in this patient is suggestive of congenital infection.2 Subependymal cysts, which were seen in this case, may result from hemorrhage, hypoxic–ischemic injury, or congenital infection.3 These cysts may also result from rare metabolic and genetic disorders and may be seen in healthy newborns. Lenticulostriate vasculopathy is the presence of hyperechogenic vessels in the basal ganglia or thalami on cranial ultrasonography. This finding may be seen in healthy infants; however, it has been associated with infectious and noninfectious conditions and is most likely a nonspecific marker of perinatal brain injury.4

Figure 2.

Chest Radiograph and Abdominal Ultrasound Image.
In this patient, chest radiography (Figure 2A) revealed a normal heart and mediastinum and clear lungs. There were thin, transverse lucent bands in the proximal humeral metaphyses bilaterally. Metaphyseal lucent bands in the neonate may result from changes associated with chronic stress or from congenital infections. Other causes of metaphyseal lucent bands include metastatic neuroblastoma and leukemia. Abdominal ultrasonography confirmed the finding of hepatosplenomegaly (Figure 2B).

Dr. Matthiesen: A slit-lamp examination revealed lamellar cataracts in both eyes, with anterior capsular plaque in the left eye. A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Congenital Rubella Syndrome\nThe newborn presented with thrombocytopenia, abnormal red reflex, and failed hearing screening. The mother had positive IgG antibodies to rubella virus, indicating past infection or vaccination. However, the mother's travel to Nigeria, where rubella vaccination coverage is not universal, raises the possibility of a recent infection during pregnancy. The newborn's symptoms, including cataracts, hearing loss, and heart problems, are consistent with congenital rubella syndrome. The presence of intracranial calcifications, hepatosplenomegaly, and metaphyseal lucent bands further support this diagnosis.""
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        ""content"": ""The newborn presents with thrombocytopenia, abnormal results on an eye examination for red reflex and on a hearing screening, scattered petechiae on the face, and increased muscle tone in the arms and legs. The mother had received treatment for malaria during the first trimester of pregnancy and had received amoxicillin\u2013clavulanate for a respiratory tract infection during the early part of the third trimester. The family lived in an urban area of Nigeria. The newborn's cranial ultrasonography showed multiple punctate, echogenic foci in the periventricular white matter bilaterally, a finding consistent with calcifications. Punctate calcifications were also present in the basal ganglia. Complex subependymal cysts were seen in the caudothalamic grooves bilaterally; these were larger on the left side than on the right side. There was mild dilatation of the left lateral ventricle. Linear, branching, echogenic foci were present in the basal ganglia bilaterally, a finding consistent with lenticulostriate vasculopathy. Chest radiography revealed thin, transverse lucent bands in the proximal humeral metaphyses bilaterally. Metaphyseal lucent bands in the neonate may result from changes associated with chronic stress or from congenital infections. Other causes of metaphyseal lucent bands include metastatic neuroblastoma and leukemia. Abdominal ultrasonography confirmed the finding of hepatosplenomegaly. A slit-lamp examination revealed lamellar cataracts in both eyes, with anterior capsular plaque in the left eye. \n\nThe differential diagnosis for this patient includes congenital infections such as toxoplasmosis, rubella, cytomegalovirus, and herpes simplex (TORCH), metabolic disorders, and genetic disorders. The patient's mother had a positive IgG test for rubella, indicating past infection or vaccination, and a negative test for cytomegalovirus. The patient's PCR test for cytomegalovirus was also negative. The patient's symptoms and findings such as thrombocytopenia, abnormal eye and hearing examinations, petechiae, increased muscle tone, cranial calcifications, and hepatosplenomegaly are consistent with a congenital infection. The patient's mother's history of malaria treatment during pregnancy and living in Nigeria, where toxoplasmosis is endemic, makes congenital toxoplasmosis a likely diagnosis. \n\nDiagnosis: Congenital Toxoplasmosis.""
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10.1056/NEJMcpc1706107,Case 3-2018: A 5-Month-Old Boy with Hypoglycemia,,Glycogen storage disease type Ia.,Glycogen storage disease type I.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:        A 5-month-old boy was admitted to the pediatric intensive care unit (ICU) of this hospital for evaluation of suspected hypoglycemia.

Figure 1.

Growth Charts.
The patient was born at another hospital after 40 weeks 4 days of gestation. His mother had had a positive 1-hour glucose challenge test and a negative 3-hour oral glucose tolerance test during pregnancy. Terminal meconium was present at delivery; the 1-minute and 5-minute Apgar scores were 8 and 9, respectively. At birth, the weight was 3.6 kg (72nd percentile) (Figure 1).

Within the patient’s first hour of life, respiratory distress developed. The blood glucose level was reportedly 4 mg per deciliter (0.2 mmol per liter) and remained low despite oral intake of formula. The patient was admitted to the special care nursery, where intravenous fluids that contained dextrose were administered; the blood glucose level normalized and the respiratory distress resolved. A blood culture was sent, and ampicillin and gentamicin were administered.

On the patient’s third day of life, the blood culture remained negative. Antibiotic agents and intravenous fluids were discontinued, breast-feeding was initiated, and a blood glucose level of more than 50 mg per deciliter (2.8 mmol per liter) was maintained. While the patient was in the special care nursery, he had occasional brief episodes of bradycardia, with heart rates between 70 and 80 beats per minute (normal heart rate in this patient’s age group, 120 to 160 beats per minute). The low heart rates were not associated with apnea or cyanosis, and each episode resolved spontaneously. In addition, the systolic blood pressure was elevated (92 to 97 mm Hg), with equal measurements in the arms and legs. Brachial–femoral delay was absent, and the results of pulse oximetry in the right hand and right foot were normal. Blood levels of electrolytes and creatinine were normal, as were the results of electrocardiography, renal ultrasonography, and newborn blood-spot screening (a panel of tests for multiple congenital diseases, primarily inborn errors of metabolism). The patient was discharged home on the seventh day of life.

The patient was well until 7 weeks of age (approximately 3.5 months before the current admission), when abdominal breathing and grunting respirations developed during the night. He had consumed a smaller volume of breast milk than usual at 6 p.m., and he awakened 3 hours later but quickly fell asleep again using a pacifier, without feeding. He slept through his usual midnight feeding, and when his mother checked on him around that time, he felt warm and seemed to be breathing heavily, with pronounced movement of the abdomen with respiration. The patient awoke at 3 a.m. and avidly consumed breast milk, but he had grunting respirations and persistent abdominal breathing that prompted his mother to take him to the emergency department of a second hospital.

On physical examination, the patient had tachypnea and a rectal temperature of 38.1°C. The white-cell count was 20,300 per cubic millimeter (reference range, 5500 to 18,000), the anion gap 26 millimoles per liter (reference range, 3 to 11), the blood bicarbonate level 9 mmol per liter (reference range, 21 to 32), and the blood glucose level 182 mg per deciliter (10.1 mmol per liter; reference range, 70 to 106 mg per deciliter [3.9 to 5.9 mmol per liter]). A blood culture was sent. The results of chest and abdominal radiography were reportedly normal. Ceftriaxone and normal saline were administered intravenously, and the patient was transferred to a third hospital for further treatment.

Table 1.

Laboratory Data.
On arrival at the third hospital, the patient fed without difficulty and appeared well. Vital signs and results of a physical examination were normal; the weight was 5.0 kg (39th percentile), and the length 57 cm (45th percentile) (Figure 1). Laboratory test results are shown in Table 1. Urinalysis revealed clear, colorless urine with a specific gravity of 1.005 and a pH of 6.0; ketones were absent. A urine culture was sent. The patient was observed for 48 hours; during that time, he appeared well and the blood and urine cultures remained negative. On the third hospital day, the patient was discharged home. His primary care pediatrician advised avoidance of intervals longer than 6 hours between feedings.

One day before the current admission, the patient’s mother called the primary care pediatrician to report the following events: when the patient awoke that morning after a 6-hour fast, he had tachypnea; he then drank a bottle of infant formula; 1 hour later, grunting respirations developed; he drank an additional ounce of formula; his ventilatory efforts normalized over the next 45 minutes; and he appeared well throughout the remainder of the day. On further recall, the patient’s mother reported that there had been one other morning within the past 2 weeks during which the patient had been irritable and had had tachypnea on awakening after a 6-hour fast, with rapid resolution of these symptoms after feeding. On the day of admission, the pediatrician had a telephone consultation with a pediatric endocrinologist, who recommended elective admission of the patient to the pediatric ICU at this hospital for a diagnostic fast.

On the patient’s admission to the pediatric ICU, history was obtained from the patient’s mother. She reported that the infant’s diet had changed from breast milk to a partially hydrolyzed cow’s milk–based infant formula between 1 and 2 weeks earlier; the patient had also recently begun eating rice cereal. His most recent feed, which consisted of approximately 105 ml of formula, had taken place 2.5 hours before admission. There had been no concerns about the patient’s growth or acquisition of developmental milestones. He had a history of a small umbilical hernia and gastroesophageal reflux disease. Medications included ranitidine and vitamin D; there were no known allergies. Immunizations were current. The patient lived with his parents, older sister, and pet dog, and he did not attend day care. His paternal grandmother had type 2 diabetes mellitus.

On physical examination, the patient was alert, smiling, and interactive. The temperature was 37.1°C, the pulse 136 beats per minute, the blood pressure 113/55 mm Hg, the respiratory rate 48 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. The weight was 7.2 kg (33rd percentile), the length 62 cm (3rd percentile), and the head circumference 41 cm (9th percentile) (Figure 1). Doll-like facies were present, with full cheeks and deep-set eyes. The abdomen was protuberant; the remainder of the examination was normal.

In preparation for the planned fast, a baseline point-of-care blood glucose level was measured, with a result of 39 mg per deciliter (2.2 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). A whole-blood specimen was obtained for measurement of the pyruvate level, and a plasma specimen was obtained for measurement of the levels of carnitine and acylcarnitines; other laboratory test results are shown in Table 1. Thirty minutes later, a point-of-care blood glucose level was 13 mg per deciliter (0.7 mmol per liter). A serum specimen was obtained for measurement of the levels of insulin, C-peptide, cortisol, human growth hormone, and free fatty acids. Glucagon was administered intramuscularly. Ten minutes later, a point-of-care blood glucose level was less than 10 mg per deciliter (<0.6 mmol per liter); other laboratory test results are shown in Table 1. The respiratory rate was 58 breaths per minute, and the results of the physical examination were otherwise unchanged. The fast was ended, and the patient drank 120 ml of formula; 1 hour later, the blood glucose level was 73 mg per deciliter (41 mmol per liter). Urinalysis revealed trace ketones.

The next morning, the insulin result became available; the level was 6.0 _IU per milliliter (reference range, 2.6 to 25.0), and the specimen was noted to be hemolyzed. Additional tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:        A 5-month-old boy was admitted to the pediatric intensive care unit (ICU) of this hospital for evaluation of suspected hypoglycemia.

Figure 1.

Growth Charts.
The patient was born at another hospital after 40 weeks 4 days of gestation. His mother had had a positive 1-hour glucose challenge test and a negative 3-hour oral glucose tolerance test during pregnancy. Terminal meconium was present at delivery; the 1-minute and 5-minute Apgar scores were 8 and 9, respectively. At birth, the weight was 3.6 kg (72nd percentile) (Figure 1).

Within the patient’s first hour of life, respiratory distress developed. The blood glucose level was reportedly 4 mg per deciliter (0.2 mmol per liter) and remained low despite oral intake of formula. The patient was admitted to the special care nursery, where intravenous fluids that contained dextrose were administered; the blood glucose level normalized and the respiratory distress resolved. A blood culture was sent, and ampicillin and gentamicin were administered.

On the patient’s third day of life, the blood culture remained negative. Antibiotic agents and intravenous fluids were discontinued, breast-feeding was initiated, and a blood glucose level of more than 50 mg per deciliter (2.8 mmol per liter) was maintained. While the patient was in the special care nursery, he had occasional brief episodes of bradycardia, with heart rates between 70 and 80 beats per minute (normal heart rate in this patient’s age group, 120 to 160 beats per minute). The low heart rates were not associated with apnea or cyanosis, and each episode resolved spontaneously. In addition, the systolic blood pressure was elevated (92 to 97 mm Hg), with equal measurements in the arms and legs. Brachial–femoral delay was absent, and the results of pulse oximetry in the right hand and right foot were normal. Blood levels of electrolytes and creatinine were normal, as were the results of electrocardiography, renal ultrasonography, and newborn blood-spot screening (a panel of tests for multiple congenital diseases, primarily inborn errors of metabolism). The patient was discharged home on the seventh day of life.

The patient was well until 7 weeks of age (approximately 3.5 months before the current admission), when abdominal breathing and grunting respirations developed during the night. He had consumed a smaller volume of breast milk than usual at 6 p.m., and he awakened 3 hours later but quickly fell asleep again using a pacifier, without feeding. He slept through his usual midnight feeding, and when his mother checked on him around that time, he felt warm and seemed to be breathing heavily, with pronounced movement of the abdomen with respiration. The patient awoke at 3 a.m. and avidly consumed breast milk, but he had grunting respirations and persistent abdominal breathing that prompted his mother to take him to the emergency department of a second hospital.

On physical examination, the patient had tachypnea and a rectal temperature of 38.1°C. The white-cell count was 20,300 per cubic millimeter (reference range, 5500 to 18,000), the anion gap 26 millimoles per liter (reference range, 3 to 11), the blood bicarbonate level 9 mmol per liter (reference range, 21 to 32), and the blood glucose level 182 mg per deciliter (10.1 mmol per liter; reference range, 70 to 106 mg per deciliter [3.9 to 5.9 mmol per liter]). A blood culture was sent. The results of chest and abdominal radiography were reportedly normal. Ceftriaxone and normal saline were administered intravenously, and the patient was transferred to a third hospital for further treatment.

Table 1.

Laboratory Data.
On arrival at the third hospital, the patient fed without difficulty and appeared well. Vital signs and results of a physical examination were normal; the weight was 5.0 kg (39th percentile), and the length 57 cm (45th percentile) (Figure 1). Laboratory test results are shown in Table 1. Urinalysis revealed clear, colorless urine with a specific gravity of 1.005 and a pH of 6.0; ketones were absent. A urine culture was sent. The patient was observed for 48 hours; during that time, he appeared well and the blood and urine cultures remained negative. On the third hospital day, the patient was discharged home. His primary care pediatrician advised avoidance of intervals longer than 6 hours between feedings.

One day before the current admission, the patient’s mother called the primary care pediatrician to report the following events: when the patient awoke that morning after a 6-hour fast, he had tachypnea; he then drank a bottle of infant formula; 1 hour later, grunting respirations developed; he drank an additional ounce of formula; his ventilatory efforts normalized over the next 45 minutes; and he appeared well throughout the remainder of the day. On further recall, the patient’s mother reported that there had been one other morning within the past 2 weeks during which the patient had been irritable and had had tachypnea on awakening after a 6-hour fast, with rapid resolution of these symptoms after feeding. On the day of admission, the pediatrician had a telephone consultation with a pediatric endocrinologist, who recommended elective admission of the patient to the pediatric ICU at this hospital for a diagnostic fast.

On the patient’s admission to the pediatric ICU, history was obtained from the patient’s mother. She reported that the infant’s diet had changed from breast milk to a partially hydrolyzed cow’s milk–based infant formula between 1 and 2 weeks earlier; the patient had also recently begun eating rice cereal. His most recent feed, which consisted of approximately 105 ml of formula, had taken place 2.5 hours before admission. There had been no concerns about the patient’s growth or acquisition of developmental milestones. He had a history of a small umbilical hernia and gastroesophageal reflux disease. Medications included ranitidine and vitamin D; there were no known allergies. Immunizations were current. The patient lived with his parents, older sister, and pet dog, and he did not attend day care. His paternal grandmother had type 2 diabetes mellitus.

On physical examination, the patient was alert, smiling, and interactive. The temperature was 37.1°C, the pulse 136 beats per minute, the blood pressure 113/55 mm Hg, the respiratory rate 48 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. The weight was 7.2 kg (33rd percentile), the length 62 cm (3rd percentile), and the head circumference 41 cm (9th percentile) (Figure 1). Doll-like facies were present, with full cheeks and deep-set eyes. The abdomen was protuberant; the remainder of the examination was normal.

In preparation for the planned fast, a baseline point-of-care blood glucose level was measured, with a result of 39 mg per deciliter (2.2 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). A whole-blood specimen was obtained for measurement of the pyruvate level, and a plasma specimen was obtained for measurement of the levels of carnitine and acylcarnitines; other laboratory test results are shown in Table 1. Thirty minutes later, a point-of-care blood glucose level was 13 mg per deciliter (0.7 mmol per liter). A serum specimen was obtained for measurement of the levels of insulin, C-peptide, cortisol, human growth hormone, and free fatty acids. Glucagon was administered intramuscularly. Ten minutes later, a point-of-care blood glucose level was less than 10 mg per deciliter (<0.6 mmol per liter); other laboratory test results are shown in Table 1. The respiratory rate was 58 breaths per minute, and the results of the physical examination were otherwise unchanged. The fast was ended, and the patient drank 120 ml of formula; 1 hour later, the blood glucose level was 73 mg per deciliter (41 mmol per liter). Urinalysis revealed trace ketones.

The next morning, the insulin result became available; the level was 6.0 _IU per milliliter (reference range, 2.6 to 25.0), and the specimen was noted to be hemolyzed. Additional tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Hyperinsulinemic hypoglycemia. This infant presents with recurrent episodes of hypoglycemia, particularly after fasting, and respiratory distress. The differential diagnosis for hypoglycemia in an infant includes hyperinsulinism, adrenal insufficiency, growth hormone deficiency, and inborn errors of metabolism. The patient's normal growth and development make growth hormone deficiency less likely. The absence of hyperpigmentation, vomiting, or other signs of adrenal crisis make adrenal insufficiency less likely. Inborn errors of metabolism typically present with more severe symptoms, including seizures, lethargy, and poor feeding, which this patient does not have. The patient's hypoglycemia responded to feeding and glucagon administration, which suggests that it is due to hyperinsulinism, as insulin inhibits glycogenolysis and gluconeogenesis. Furthermore, the patient's insulin level was inappropriately high for his low blood glucose level, confirming the diagnosis of hyperinsulinemic hypoglycemia.""
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10.1056/NEJMcpc1701763,Case 2-2018: A 41-Year-Old Woman with Vision Disturbances and Headache,,Intracranial hypertension associated with systemic lupus erythematosus and glucocorticoid use.,"Intracranial hypertension associated with systemic lupus erythematosus, with a possible contribution of glucocorticoid use.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:          A 41-year-old woman was evaluated in the rheumatology clinic of this hospital because of headaches and a 6-week history of intermittent, transient vision loss.

Four years before the current presentation, a skin eruption on the right foot and a lesion on the tongue developed. A biopsy of both lesions was performed at another hospital; examination of the specimens revealed evidence of leukocytoclastic vasculitis. Prednisone, methotrexate, mycophenolate mofetil, and azathioprine were administered, and the mucocutaneous lesions improved, but they recurred after any attempt to taper the immunosuppressive medications.

Twenty-one months before the current presentation, headaches developed and skin lesions recurred. The headaches were generally located in the right temporal area, were characterized as throbbing, and lasted approximately 5 to 10 minutes. The patient was evaluated at the other hospital, and magnetic resonance imaging (MRI) of the head with contrast enhancement was performed.

Figure 1.

MRI of the Head Obtained 21 Months before Presentation.
Dr. Mary E. Cunnane: Axial, T2-weighted fluid-attenuated inversion recovery (FLAIR) images showed hyperintensity in the right thalamocapsular region and right midbrain, with patchy enhancement of the right midbrain (Figure 1).

Dr. Stone: A lumbar puncture was performed. On cerebrospinal fluid (CSF) analysis, the protein level was 54 mg per deciliter (reference range, 5 to 55) and the total nucleated-cell count was 16 per cubic millimeter, with 66% lymphocytes. The opening pressure was not measured. A test for cryptococcal antigen and nucleic-acid tests for toxoplasma, JC virus, herpes simplex virus types I and II, and varicella–zoster virus were negative. Flow cytometry did not show any abnormal cell populations. Screening tests for human immunodeficiency virus and syphilis were negative. A presumptive diagnosis of central nervous system (CNS) vasculitis was made. Prednisone, cyclophosphamide, rituximab, and hydroxychloroquine were administered, and the headaches improved temporarily. Two months later, repeat MRI of the head reportedly showed resolution of the hyperintensity that had been seen previously.

Eighteen months before the current presentation, the patient was referred to the rheumatology clinic at this hospital for the evaluation of recurrent painful mucocutaneous lesions of the hands, feet, and mouth. She also reported fatigue and arthralgias of the hands, knees, and ankles. Blood tests revealed antinuclear antibodies (at a titer of >1:5120, with a speckled pattern) and anti-Ro antibodies (154.60 optical-density units; normal range, <19.99), as well as hypocomplementemia. A diagnosis of systemic lupus erythematosus (SLE) was suspected. Prednisone and hydroxychloroquine were continued, and mycophenolate mofetil was added to the regimen. Cyclophosphamide and rituximab were stopped. Over the next 15 months, the patient had exacerbations of the cutaneous vasculitis whenever the prednisone dose was tapered.

Three months before the current presentation, the prednisone dose was increased because of worsening lesions on the hands and feet. During the 6 weeks before this presentation, sporadic episodes of transient vision loss occurred. The episodes lasted 5 to 10 seconds, occurred one to several times per day, and remitted spontaneously. They were associated with dizziness, pulsatile tinnitus, and headaches. The headaches reportedly worsened with changes in position, such as bending over, but there appeared to be no relationship between the headaches and time of day, diet, activity, or performance of the Valsalva maneuver.

The patient was evaluated by an ophthalmologist 1 week before the current presentation and then evaluated by her neurologist at another facility 6 days later. On neurologic evaluation, the blood pressure was 114/72 mm Hg. Bilateral optic-disk swelling was noted, but the remainder of the examination was reportedly normal. MRI of the head was performed.

One day later, the patient was evaluated by her rheumatologist at this hospital. She reported ongoing mucocutaneous symptoms, including painful swelling on the right lip, a painful ulcer on the palate, and pruritic lesions on the feet. There was no diplopia, neck stiffness, photophobia, sonophobia, general or focal weakness, paresthesia, ataxia, syncope, fever, weight loss, nausea, vomiting, or bowel or bladder dysfunction.

The patient’s medical history was notable for weight gain of 22.7 kg over a 4-year period in the context of glucocorticoid treatment and glucocorticoid-related osteoporosis. Her medications included prednisone, hydroxychloroquine, mycophenolate mofetil, alendronate, calcium, and vitamin D. Rituximab had been readministered 9 days earlier.

The patient was originally from the eastern Mediterranean and had immigrated to the United States 20 years earlier. She was divorced and had one adolescent son. She had previously worked in the restaurant business but had to discontinue this work because of physical limitations. She had an 8.5-pack-year history of cigarette smoking and continued to smoke several cigarettes a day, but she did not drink alcohol or use illicit drugs. Her mother had coronary artery disease, her father had valvular heart disease, and her maternal grandmother had had a stroke. Her sisters were healthy, and there was no family history of neurologic, ophthalmologic, or rheumatologic disease.

Table 1.

Laboratory Data.
On examination, the temperature was 37°C, the pulse 109 beats per minute, the blood pressure 129/78 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The weight was 94 kg. The patient appeared mildly unwell, was tearful, and had cushingoid features. The bilateral optic-disk swelling was confirmed, but the remainder of the neurologic examination was normal. A small pink lump was noted on the right upper lip, and an ulcer was present on the hard palate. There were multiple splinterlike ulcerations on the fingers, nonblanching tender patches with a livedoid pattern and excoriations on the toes, and purple papules on the feet. Laboratory test results obtained 9 days before the current presentation are shown in Table 1.

The patient was referred for an ophthalmologic examination. Visual acuity without glasses was 20/15 in the right eye and 20/15 in the left eye. The pupils were equal in size and had a normal response to light. Results of testing with the use of an Amsler grid and an Ishihara color plate were within normal limits. Humphrey visual-field testing revealed enlarged blind spots in both eyes. Applanation tonometry revealed an intraocular pressure of 11 mm Hg in the right eye and 10 mm Hg in the left eye. On external examination, the eyelids and ocular adnexa were normal. Results of a slit-lamp biomicroscopic examination were normal in both eyes. A dilated-pupil fundus examination revealed extensive bilateral optic-disk edema (grade 4 on the Frisén scale, which ranges from 0 to 5, with higher grades indicating more severe edema) and associated subretinal fluid, as well as peripapillary folds in the left eye and multiple peripapillary hemorrhages in both eyes. There were splinter and subretinal hemorrhages and changes in the macular pigment in both eyes.

A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  A 41-year-old woman was evaluated in the rheumatology clinic of this hospital because of headaches and a 6-week history of intermittent, transient vision loss.

Four years before the current presentation, a skin eruption on the right foot and a lesion on the tongue developed. A biopsy of both lesions was performed at another hospital; examination of the specimens revealed evidence of leukocytoclastic vasculitis. Prednisone, methotrexate, mycophenolate mofetil, and azathioprine were administered, and the mucocutaneous lesions improved, but they recurred after any attempt to taper the immunosuppressive medications.

Twenty-one months before the current presentation, headaches developed and skin lesions recurred. The headaches were generally located in the right temporal area, were characterized as throbbing, and lasted approximately 5 to 10 minutes. The patient was evaluated at the other hospital, and magnetic resonance imaging (MRI) of the head with contrast enhancement was performed.

Figure 1.

MRI of the Head Obtained 21 Months before Presentation.
Dr. Mary E. Cunnane: Axial, T2-weighted fluid-attenuated inversion recovery (FLAIR) images showed hyperintensity in the right thalamocapsular region and right midbrain, with patchy enhancement of the right midbrain (Figure 1).

Dr. Stone: A lumbar puncture was performed. On cerebrospinal fluid (CSF) analysis, the protein level was 54 mg per deciliter (reference range, 5 to 55) and the total nucleated-cell count was 16 per cubic millimeter, with 66% lymphocytes. The opening pressure was not measured. A test for cryptococcal antigen and nucleic-acid tests for toxoplasma, JC virus, herpes simplex virus types I and II, and varicella–zoster virus were negative. Flow cytometry did not show any abnormal cell populations. Screening tests for human immunodeficiency virus and syphilis were negative. A presumptive diagnosis of central nervous system (CNS) vasculitis was made. Prednisone, cyclophosphamide, rituximab, and hydroxychloroquine were administered, and the headaches improved temporarily. Two months later, repeat MRI of the head reportedly showed resolution of the hyperintensity that had been seen previously.

Eighteen months before the current presentation, the patient was referred to the rheumatology clinic at this hospital for the evaluation of recurrent painful mucocutaneous lesions of the hands, feet, and mouth. She also reported fatigue and arthralgias of the hands, knees, and ankles. Blood tests revealed antinuclear antibodies (at a titer of >1:5120, with a speckled pattern) and anti-Ro antibodies (154.60 optical-density units; normal range, <19.99), as well as hypocomplementemia. A diagnosis of systemic lupus erythematosus (SLE) was suspected. Prednisone and hydroxychloroquine were continued, and mycophenolate mofetil was added to the regimen. Cyclophosphamide and rituximab were stopped. Over the next 15 months, the patient had exacerbations of the cutaneous vasculitis whenever the prednisone dose was tapered.

Three months before the current presentation, the prednisone dose was increased because of worsening lesions on the hands and feet. During the 6 weeks before this presentation, sporadic episodes of transient vision loss occurred. The episodes lasted 5 to 10 seconds, occurred one to several times per day, and remitted spontaneously. They were associated with dizziness, pulsatile tinnitus, and headaches. The headaches reportedly worsened with changes in position, such as bending over, but there appeared to be no relationship between the headaches and time of day, diet, activity, or performance of the Valsalva maneuver.

The patient was evaluated by an ophthalmologist 1 week before the current presentation and then evaluated by her neurologist at another facility 6 days later. On neurologic evaluation, the blood pressure was 114/72 mm Hg. Bilateral optic-disk swelling was noted, but the remainder of the examination was reportedly normal. MRI of the head was performed.

One day later, the patient was evaluated by her rheumatologist at this hospital. She reported ongoing mucocutaneous symptoms, including painful swelling on the right lip, a painful ulcer on the palate, and pruritic lesions on the feet. There was no diplopia, neck stiffness, photophobia, sonophobia, general or focal weakness, paresthesia, ataxia, syncope, fever, weight loss, nausea, vomiting, or bowel or bladder dysfunction.

The patient’s medical history was notable for weight gain of 22.7 kg over a 4-year period in the context of glucocorticoid treatment and glucocorticoid-related osteoporosis. Her medications included prednisone, hydroxychloroquine, mycophenolate mofetil, alendronate, calcium, and vitamin D. Rituximab had been readministered 9 days earlier.

The patient was originally from the eastern Mediterranean and had immigrated to the United States 20 years earlier. She was divorced and had one adolescent son. She had previously worked in the restaurant business but had to discontinue this work because of physical limitations. She had an 8.5-pack-year history of cigarette smoking and continued to smoke several cigarettes a day, but she did not drink alcohol or use illicit drugs. Her mother had coronary artery disease, her father had valvular heart disease, and her maternal grandmother had had a stroke. Her sisters were healthy, and there was no family history of neurologic, ophthalmologic, or rheumatologic disease.

Table 1.

Laboratory Data.
On examination, the temperature was 37°C, the pulse 109 beats per minute, the blood pressure 129/78 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The weight was 94 kg. The patient appeared mildly unwell, was tearful, and had cushingoid features. The bilateral optic-disk swelling was confirmed, but the remainder of the neurologic examination was normal. A small pink lump was noted on the right upper lip, and an ulcer was present on the hard palate. There were multiple splinterlike ulcerations on the fingers, nonblanching tender patches with a livedoid pattern and excoriations on the toes, and purple papules on the feet. Laboratory test results obtained 9 days before the current presentation are shown in Table 1.

The patient was referred for an ophthalmologic examination. Visual acuity without glasses was 20/15 in the right eye and 20/15 in the left eye. The pupils were equal in size and had a normal response to light. Results of testing with the use of an Amsler grid and an Ishihara color plate were within normal limits. Humphrey visual-field testing revealed enlarged blind spots in both eyes. Applanation tonometry revealed an intraocular pressure of 11 mm Hg in the right eye and 10 mm Hg in the left eye. On external examination, the eyelids and ocular adnexa were normal. Results of a slit-lamp biomicroscopic examination were normal in both eyes. A dilated-pupil fundus examination revealed extensive bilateral optic-disk edema (grade 4 on the Frisén scale, which ranges from 0 to 5, with higher grades indicating more severe edema) and associated subretinal fluid, as well as peripapillary folds in the left eye and multiple peripapillary hemorrhages in both eyes. There were splinter and subretinal hemorrhages and changes in the macular pigment in both eyes.

A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 41-year-old woman with a history of leukocytoclastic vasculitis and suspected systemic lupus erythematosus (SLE) who presents with headaches, transient vision loss, and recurrent mucocutaneous lesions. The differential diagnosis for this patient includes central nervous system (CNS) vasculitis, SLE, idiopathic intracranial hypertension (IIH), and Behcet's disease. \n\nCNS vasculitis was previously suspected due to the patient's history of headaches and abnormal MRI findings. However, the patient's symptoms improved temporarily with immunosuppressive therapy and repeat MRI reportedly showed resolution of the hyperintensity. This makes CNS vasculitis less likely. \n\nSLE is a possibility given the patient's positive antinuclear antibodies, anti-Ro antibodies, and hypocomplementemia. However, the patient's symptoms did not improve with immunosuppressive therapy typically used for SLE, making this diagnosis less likely. \n\nIIH, also known as pseudotumor cerebri, is a condition characterized by increased intracranial pressure, which can cause headaches and vision loss. The patient's symptoms of transient vision loss, headaches, and pulsatile tinnitus, as well as the finding of bilateral optic disk swelling, are suggestive of IIH. However, the patient's CSF analysis did not show elevated protein or cell count, which would be expected in IIH. \n\nBehcet's disease is a rare disorder characterized by inflammation of blood vessels throughout the body. It can cause a variety of symptoms, including mucocutaneous lesions, headaches, and vision problems. The patient's recurrent painful mucocutaneous lesions of the hands, feet, and mouth, as well as her headaches and vision loss, are consistent with Behcet's disease. \n\nDiagnosis:\nThe most likely diagnosis is Behcet's disease.""
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}",Behcet's disease,N
10.1056/NEJMcpc1712222,"Case 1-2018: A 39-Year-Old Woman with Rapidly Progressive Respiratory Failure
List of authors.",,"Adenovirus infection, disseminated.",Viral pneumonia and bronchiolitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:      A 39-year-old woman with a history of leukemia and double-unit cord-blood transplantation was admitted to this hospital because of dyspnea, hypoxemia, and the presence of infiltrates in both lungs.

Thirty months before this admission, the patient presented to another hospital with upper respiratory symptoms, throat swelling, and anemia. On the basis of the results of a bone marrow biopsy, a diagnosis of acute myeloid leukemia was made. Induction chemotherapy with idarubicin and cytarabine was administered, followed by consolidation chemotherapy with three cycles of high-dose cytarabine. Subsequently, the patient was in complete remission.

One year later, a relapse of acute myeloid leukemia occurred, and mitoxantrone, etoposide, and cytarabine were administered. Two months later, fever, fatigue, pleuritic chest pain, and dry cough developed, and the patient presented to a second hospital. Computed tomography (CT) of the chest, performed after the administration of contrast material, reportedly revealed multifocal nodular opacities, and the patient was treated with vancomycin. She was transferred to the first hospital, where a CT-guided lung biopsy was performed. Pathological examination of the biopsy specimen revealed hyphae with septations, a finding that was consistent with invasive aspergillus infection. Micafungin was administered, followed by voriconazole, for a total of 12 months thereafter.

Six weeks after the lung biopsy was performed (approximately 14 months before this admission), the patient was admitted to this hospital for bone marrow transplantation. After she received a conditioning chemotherapy regimen of fludarabine and melphalan, a double-unit cord-blood transplantation was performed. The hospital course after transplantation was complicated by Staphylococcus aureus bacteremia, respiratory failure that led to mechanical ventilation, acute kidney injury that led to temporary hemodialysis, and duodenal graft-versus-host disease (GVHD) that was treated with glucocorticoids, sirolimus, and mycophenolate mofetil. Results of a bone marrow biopsy that was performed 100 days after the transplantation were consistent with complete remission, with no evidence of recurrent leukemia.

Four months before this admission, sore throat, odynophagia, and cough occurred and were thought to be caused by recurrent tonsillitis. Three courses of antimicrobial therapy (including cefuroxime and amoxicillin–clavulanic acid) were administered, and 3 months later, a tonsillectomy was performed at an affiliated hospital.

Seven days before this admission, after a 2-day summer camping trip in New England, fatigue, progressive dyspnea, and diffuse myalgias occurred, followed by chills, nasal congestion, rhinorrhea, rigors, and fever (to a temperature of 38.7°C). On examination in the emergency department of the second hospital, the patient had hypoxemia, with an oxygen saturation of 85% while she was breathing ambient air. CT of the chest, performed after the administration of contrast material, revealed new bilateral ground-glass opacities and mediastinal and hilar lymphadenopathy. Levofloxacin and piperacillin–tazobactam were administered intravenously. Approximately 20 hours after presentation, the patient was transferred to this hospital.

During the previous week, the patient had had loose, nonbloody stools and abdominal pain, with no other abdominal symptoms, cough, sputum production, headache, rash, or arthralgias. She had hypothyroidism, asthma, hypertension, diabetes, and depression; in the past, she had had a catheter-associated thrombus of the right subclavian vein and had undergone a cesarean section. Medications were acyclovir, trimethoprim–sulfamethoxazole, montelukast, amlodipine, aripiprazole, sertraline, levothyroxine, and zolpidem, as well as an albuterol inhaler as needed. She was allergic to house dust mites. She reported that she had had no tick bites or animal exposures during the recent camping trip and had had no known sick contacts. The patient worked in a hair salon and lived with her son. She drank alcohol socially, had smoked cigarettes for 3 years in the past, and did not use illicit drugs. Her father had had melanoma, and her paternal grandfather had had rheumatoid arthritis. There was no other family history of cancer.

On examination, the patient appeared to be anxious and in moderate respiratory distress. The temperature was 36.8°C, the pulse 91 beats per minute, the blood pressure 123/72 mm Hg, and the respiratory rate 24 breaths per minute. The oxygen saturation was 90% while she was breathing oxygen through a nasal cannula at a rate of 6 liters per minute, 92% while she was using a nonrebreather face mask, and 94% while she was breathing high-flow oxygen through a nasal cannula at a rate of 40 liters per minute. She had scattered fine crackles, wheezes, and high-pitched inspiratory “squeaks” and “pops” in both lungs diffusely. There was very mild tenderness in the mid-epigastrium. The remainder of the examination was normal.

Table 1.

Laboratory Data.
On admission, vancomycin, piperacillin–tazobactam, levofloxacin, furosemide, and methylprednisone were administered intravenously, and ipratropium–albuterol was administered by inhalation. The prothrombin time and prothrombin-time international normalized ratio were normal; other test results are shown in Table 1. Cultures of the sputum, urine, and blood were performed. Testing for legionella and Pneumocystis jirovecii in the sputum and legionella antigen in the urine was negative, as was nucleic-acid testing for influenza A and B and respiratory syncytial virus.

Figure 1.

Imaging Studies of the Chest.
Dr. Jo-Anne O. Shepard: On admission, chest radiography (Figure 1A) revealed a faint patchy opacity in the left upper lobe and trace bilateral pleural effusions. Chest CT (Figure 1B, 1C, and 1D), performed after the administration of contrast material, revealed bilateral ground-glass opacities predominantly in the upper lobes, opacities in small airways of the lower lobes that were consistent with mucous plugging, bronchial-wall thickening, and bilateral pulmonary nodules that had progressed since the previous CT study had been obtained (at the second hospital 2 days earlier). A small nodule in the right upper lobe represented a scar from the previous aspergillus infection. Enlarged mediastinal lymph nodes and trace bilateral pleural effusions were also noted.

Dr. Chivukula: Eight hours after admission, the patient had a dry cough, progressive dyspnea, increased crackles on lung auscultation, and worsened hypoxemia, with an intermittent decline in the oxygen saturation to 75% despite the delivery of high-flow oxygen. Ceftazidime was administered intravenously, and the patient was transferred to the intensive care unit (ICU). Twenty-two hours after admission, an endotracheal tube was placed and mechanical ventilation was initiated. Bronchoscopic examination revealed thin, foamy secretions in the left and right bronchi, with mild, diffuse airway erythema. Bronchoalveolar-lavage fluid was obtained from the right upper lobe and left upper lobe.

Diagnostic test results were received.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:            A 39-year-old woman with a history of leukemia and double-unit cord-blood transplantation was admitted to this hospital because of dyspnea, hypoxemia, and the presence of infiltrates in both lungs.

Thirty months before this admission, the patient presented to another hospital with upper respiratory symptoms, throat swelling, and anemia. On the basis of the results of a bone marrow biopsy, a diagnosis of acute myeloid leukemia was made. Induction chemotherapy with idarubicin and cytarabine was administered, followed by consolidation chemotherapy with three cycles of high-dose cytarabine. Subsequently, the patient was in complete remission.

One year later, a relapse of acute myeloid leukemia occurred, and mitoxantrone, etoposide, and cytarabine were administered. Two months later, fever, fatigue, pleuritic chest pain, and dry cough developed, and the patient presented to a second hospital. Computed tomography (CT) of the chest, performed after the administration of contrast material, reportedly revealed multifocal nodular opacities, and the patient was treated with vancomycin. She was transferred to the first hospital, where a CT-guided lung biopsy was performed. Pathological examination of the biopsy specimen revealed hyphae with septations, a finding that was consistent with invasive aspergillus infection. Micafungin was administered, followed by voriconazole, for a total of 12 months thereafter.

Six weeks after the lung biopsy was performed (approximately 14 months before this admission), the patient was admitted to this hospital for bone marrow transplantation. After she received a conditioning chemotherapy regimen of fludarabine and melphalan, a double-unit cord-blood transplantation was performed. The hospital course after transplantation was complicated by Staphylococcus aureus bacteremia, respiratory failure that led to mechanical ventilation, acute kidney injury that led to temporary hemodialysis, and duodenal graft-versus-host disease (GVHD) that was treated with glucocorticoids, sirolimus, and mycophenolate mofetil. Results of a bone marrow biopsy that was performed 100 days after the transplantation were consistent with complete remission, with no evidence of recurrent leukemia.

Four months before this admission, sore throat, odynophagia, and cough occurred and were thought to be caused by recurrent tonsillitis. Three courses of antimicrobial therapy (including cefuroxime and amoxicillin–clavulanic acid) were administered, and 3 months later, a tonsillectomy was performed at an affiliated hospital.

Seven days before this admission, after a 2-day summer camping trip in New England, fatigue, progressive dyspnea, and diffuse myalgias occurred, followed by chills, nasal congestion, rhinorrhea, rigors, and fever (to a temperature of 38.7°C). On examination in the emergency department of the second hospital, the patient had hypoxemia, with an oxygen saturation of 85% while she was breathing ambient air. CT of the chest, performed after the administration of contrast material, revealed new bilateral ground-glass opacities and mediastinal and hilar lymphadenopathy. Levofloxacin and piperacillin–tazobactam were administered intravenously. Approximately 20 hours after presentation, the patient was transferred to this hospital.

During the previous week, the patient had had loose, nonbloody stools and abdominal pain, with no other abdominal symptoms, cough, sputum production, headache, rash, or arthralgias. She had hypothyroidism, asthma, hypertension, diabetes, and depression; in the past, she had had a catheter-associated thrombus of the right subclavian vein and had undergone a cesarean section. Medications were acyclovir, trimethoprim–sulfamethoxazole, montelukast, amlodipine, aripiprazole, sertraline, levothyroxine, and zolpidem, as well as an albuterol inhaler as needed. She was allergic to house dust mites. She reported that she had had no tick bites or animal exposures during the recent camping trip and had had no known sick contacts. The patient worked in a hair salon and lived with her son. She drank alcohol socially, had smoked cigarettes for 3 years in the past, and did not use illicit drugs. Her father had had melanoma, and her paternal grandfather had had rheumatoid arthritis. There was no other family history of cancer.

On examination, the patient appeared to be anxious and in moderate respiratory distress. The temperature was 36.8°C, the pulse 91 beats per minute, the blood pressure 123/72 mm Hg, and the respiratory rate 24 breaths per minute. The oxygen saturation was 90% while she was breathing oxygen through a nasal cannula at a rate of 6 liters per minute, 92% while she was using a nonrebreather face mask, and 94% while she was breathing high-flow oxygen through a nasal cannula at a rate of 40 liters per minute. She had scattered fine crackles, wheezes, and high-pitched inspiratory “squeaks” and “pops” in both lungs diffusely. There was very mild tenderness in the mid-epigastrium. The remainder of the examination was normal.

Table 1.

Laboratory Data.
On admission, vancomycin, piperacillin–tazobactam, levofloxacin, furosemide, and methylprednisone were administered intravenously, and ipratropium–albuterol was administered by inhalation. The prothrombin time and prothrombin-time international normalized ratio were normal; other test results are shown in Table 1. Cultures of the sputum, urine, and blood were performed. Testing for legionella and Pneumocystis jirovecii in the sputum and legionella antigen in the urine was negative, as was nucleic-acid testing for influenza A and B and respiratory syncytial virus.

Figure 1.

Imaging Studies of the Chest.
Dr. Jo-Anne O. Shepard: On admission, chest radiography (Figure 1A) revealed a faint patchy opacity in the left upper lobe and trace bilateral pleural effusions. Chest CT (Figure 1B, 1C, and 1D), performed after the administration of contrast material, revealed bilateral ground-glass opacities predominantly in the upper lobes, opacities in small airways of the lower lobes that were consistent with mucous plugging, bronchial-wall thickening, and bilateral pulmonary nodules that had progressed since the previous CT study had been obtained (at the second hospital 2 days earlier). A small nodule in the right upper lobe represented a scar from the previous aspergillus infection. Enlarged mediastinal lymph nodes and trace bilateral pleural effusions were also noted.

Dr. Chivukula: Eight hours after admission, the patient had a dry cough, progressive dyspnea, increased crackles on lung auscultation, and worsened hypoxemia, with an intermittent decline in the oxygen saturation to 75% despite the delivery of high-flow oxygen. Ceftazidime was administered intravenously, and the patient was transferred to the intensive care unit (ICU). Twenty-two hours after admission, an endotracheal tube was placed and mechanical ventilation was initiated. Bronchoscopic examination revealed thin, foamy secretions in the left and right bronchi, with mild, diffuse airway erythema. Bronchoalveolar-lavage fluid was obtained from the right upper lobe and left upper lobe.

Diagnostic test results were received.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 39-year-old woman with a history of acute myeloid leukemia, double-unit cord-blood transplantation, and invasive aspergillus infection. She presents with dyspnea, hypoxemia, and bilateral lung infiltrates. The differential diagnosis includes bacterial pneumonia, fungal pneumonia, viral pneumonia, and non-infectious causes such as pulmonary edema, acute respiratory distress syndrome (ARDS), and drug-induced lung disease. Given her history of invasive aspergillus infection, a recurrence of this infection is also possible. However, the patient's symptoms started after a camping trip, which could suggest an exposure to a new infectious agent. The patient's immunocompromised status due to her history of leukemia and transplantation makes her susceptible to a wide range of infections. The patient's CT scan shows bilateral ground-glass opacities, mucous plugging, bronchial-wall thickening, and bilateral pulmonary nodules, which are nonspecific findings that could be seen in many types of pneumonia as well as non-infectious lung diseases. The patient's sputum, urine, and blood cultures were negative, as were tests for legionella, Pneumocystis jirovecii, influenza A and B, and respiratory syncytial virus. This makes bacterial, Pneumocystis, and these viral pneumonias less likely. The patient's symptoms did not improve with broad-spectrum antibiotics, which makes bacterial pneumonia less likely. The patient's history of invasive aspergillus infection and her immunocompromised status make a recurrence of this infection a possibility. However, the patient's symptoms started after a camping trip, which could suggest an exposure to a new infectious agent such as a fungal or parasitic infection. Given the patient's history and the progression of her symptoms, a fungal pneumonia such as a new aspergillus infection or another type of fungal infection is the most likely diagnosis.\n\nDiagnosis: Fungal pneumonia.""
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10.1056/NEJMcpc1710566,"Case 40-2017 — A 32-Year-Old Woman with Headache, Abdominal Pain, Anemia, and Thrombocytopenia",,Paroxysmal nocturnal hemoglobinuria.,Paroxysmal nocturnal hemoglobinuria.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:       A 32-year-old woman was admitted to this hospital in the fall because of severe headache and loss of peripheral vision.

The patient had been in her usual state of health until 4 weeks before admission to this hospital, when she underwent elective termination of pregnancy with methotrexate. The pregnancy had occurred despite the presence of an intrauterine device, and the device was removed a few days after the termination. Oral contraception was initiated.

Table 1.

Laboratory Data.
Three weeks later and 1 week before admission to this hospital, pain in the left upper quadrant, vaginal bleeding, and headache developed. The patient was admitted to another hospital. The blood level of human chorionic gonadotropin was 24 IU per liter (normal range, <6 IU per liter); the level had been 21,000 IU per liter 3 weeks earlier, when she was pregnant. Blood levels of electrolytes, glucose, amylase, lipase, total protein, and albumin were normal, as were results of renal-function tests, the prothrombin time, the international normalized ratio, and the partial-thromboplastin time. An examination of a peripheral-blood smear for babesia and a direct antiglobulin test were negative; other laboratory test results are shown in Table 1. Imaging studies were obtained.

Figure 1.

CT Scan of the Abdomen.
Dr. R. Gilberto Gonzalez: Computed tomography (CT) of the abdomen and pelvis (Figure 1), performed after the administration of intravenous contrast material, revealed splenomegaly (spleen length, 15.6 cm in the craniocaudal dimension; normal range, ≤12 cm), as well as a central filling defect in the splenic vein that was compatible with acute splenic-vein thrombosis. CT of the chest, performed after the administration of intravenous contrast material, revealed low lung volumes, scattered ground-glass opacities, and no evidence of pulmonary embolism.

Dr. McGrath: Oral contraception was stopped. On the third hospital day, the patient’s abdominal pain diminished, and she was discharged home.

Four days later, severe bifrontal headache and loss of vision in the left visual field developed. The patient was evaluated by her primary care physician. On examination, she had decreased peripheral vision superiorly and inferiorly in the left visual field. Magnetic resonance imaging (MRI) of the head was scheduled, but the severity of her headaches increased, and she was evaluated at the other hospital. Additional imaging studies were obtained.

Figure 2.

Imaging Studies of the Head.
Dr. Gonzalez: CT of the head and neck (Figure 2) revealed a confluent area of hypodensity and sulcal effacement involving the superior right parietal lobe that extended inferiorly into the right occipital lobe and the right aspect of the splenium of the corpus callosum (a finding suggestive of a recent infarct) and small, focal areas of hyperdensity (findings consistent with hemorrhagic conversion). Although a focal occlusive thrombus was not identified, the distal branches of the right posterior cerebral veins were not visible. The patient was transferred to the emergency department of this hospital.

Dr. McGrath: On evaluation in the emergency department, the patient reported persistent headache, vision changes in the left visual field, photophobia, phonophobia, and pain with extraocular movements. She had a history of chronic back pain that was related to a vertebral disk herniation, for which she had undergone spinal-fusion surgery 4 years before admission to this hospital. During the 3 years before admission, she had had two episodes of self-limited thrombocytopenia that were thought to be associated with methotrexate treatment for an unknown skin disorder. She had no history of bleeding or clotting disorders and had had no spontaneous miscarriages. She had a 2-year history of waxing-and-waning dull epigastric pain that was associated with nausea and occasional episodes of bilious emesis; the pain partially improved with omeprazole.

The patient’s medications included diclofenac, baclofen, controlled-release morphine sulfate, hydrocodone–acetaminophen, and omeprazole. She had taken oral contraception in the past for extended periods of time. She lived in coastal New England and worked in communications. She drank alcohol occasionally and smoked less than 1 pack of cigarettes per week; she had not smoked during the past few months. She did not use illicit drugs, over-the-counter medications, or herbal medications. There was no family history of bleeding or clotting disorders, spontaneous miscarriage, or hematologic cancer.

On examination, the temperature was 38.3°C, the blood pressure 126/72 mm Hg, the pulse 54 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. She was in mild distress because of her headache, but she was alert and oriented to time and place. Examination of the neck, heart, lungs, abdomen, skin, and oral mucosa was normal. Left homonymous hemianopia was present; other cranial-nerve functions were normal, although function of the first cranial nerve was not tested. Strength, sensation to light touch, and deep-tendon reflexes of the arms and legs were normal. Finger–nose–finger testing showed no dysmetria. Examination of a peripheral-blood smear showed 0 to 2 schistocytes per high-power field, teardrop and pencil cells, occasional large platelets, and normal-appearing white cells. Urinalysis showed 1+ ketones, 2+ blood, 1+ protein, 1+ urobilinogen, a specific gravity greater than 1.040 (normal range, 1.001 to 1.035), and a pH of 5 (normal range, 5 to 9) by dipstick; microscopic examination of the sediment revealed no red cells and 3 to 5 white cells per high-power field (normal range, 0 to 2). Other laboratory test results are shown in Table 1. The patient was admitted to the intensive care unit of this hospital, and additional imaging studies were obtained.

Dr. Gonzalez: MRI of the head confirmed the infarcts and hemorrhagic conversion that had been seen on CT angiography and venography (Figure 2). A cortical vein was not visible over the lesion, which suggested either cortical-vein thrombosis or secondary compression due to mass effect of the parenchymal lesion. On the second hospital day, transfemoral cerebral angiography (Figure 2) showed multiple cerebral venous thromboses involving the right frontal and parietal cortical veins, with no involvement of the major dural sinuses.

Dr. McGrath: A diagnostic test was performed, and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:         A 32-year-old woman was admitted to this hospital in the fall because of severe headache and loss of peripheral vision.

The patient had been in her usual state of health until 4 weeks before admission to this hospital, when she underwent elective termination of pregnancy with methotrexate. The pregnancy had occurred despite the presence of an intrauterine device, and the device was removed a few days after the termination. Oral contraception was initiated.

Table 1.

Laboratory Data.
Three weeks later and 1 week before admission to this hospital, pain in the left upper quadrant, vaginal bleeding, and headache developed. The patient was admitted to another hospital. The blood level of human chorionic gonadotropin was 24 IU per liter (normal range, <6 IU per liter); the level had been 21,000 IU per liter 3 weeks earlier, when she was pregnant. Blood levels of electrolytes, glucose, amylase, lipase, total protein, and albumin were normal, as were results of renal-function tests, the prothrombin time, the international normalized ratio, and the partial-thromboplastin time. An examination of a peripheral-blood smear for babesia and a direct antiglobulin test were negative; other laboratory test results are shown in Table 1. Imaging studies were obtained.

Figure 1.

CT Scan of the Abdomen.
Dr. R. Gilberto Gonzalez: Computed tomography (CT) of the abdomen and pelvis (Figure 1), performed after the administration of intravenous contrast material, revealed splenomegaly (spleen length, 15.6 cm in the craniocaudal dimension; normal range, ≤12 cm), as well as a central filling defect in the splenic vein that was compatible with acute splenic-vein thrombosis. CT of the chest, performed after the administration of intravenous contrast material, revealed low lung volumes, scattered ground-glass opacities, and no evidence of pulmonary embolism.

Dr. McGrath: Oral contraception was stopped. On the third hospital day, the patient’s abdominal pain diminished, and she was discharged home.

Four days later, severe bifrontal headache and loss of vision in the left visual field developed. The patient was evaluated by her primary care physician. On examination, she had decreased peripheral vision superiorly and inferiorly in the left visual field. Magnetic resonance imaging (MRI) of the head was scheduled, but the severity of her headaches increased, and she was evaluated at the other hospital. Additional imaging studies were obtained.

Figure 2.

Imaging Studies of the Head.
Dr. Gonzalez: CT of the head and neck (Figure 2) revealed a confluent area of hypodensity and sulcal effacement involving the superior right parietal lobe that extended inferiorly into the right occipital lobe and the right aspect of the splenium of the corpus callosum (a finding suggestive of a recent infarct) and small, focal areas of hyperdensity (findings consistent with hemorrhagic conversion). Although a focal occlusive thrombus was not identified, the distal branches of the right posterior cerebral veins were not visible. The patient was transferred to the emergency department of this hospital.

Dr. McGrath: On evaluation in the emergency department, the patient reported persistent headache, vision changes in the left visual field, photophobia, phonophobia, and pain with extraocular movements. She had a history of chronic back pain that was related to a vertebral disk herniation, for which she had undergone spinal-fusion surgery 4 years before admission to this hospital. During the 3 years before admission, she had had two episodes of self-limited thrombocytopenia that were thought to be associated with methotrexate treatment for an unknown skin disorder. She had no history of bleeding or clotting disorders and had had no spontaneous miscarriages. She had a 2-year history of waxing-and-waning dull epigastric pain that was associated with nausea and occasional episodes of bilious emesis; the pain partially improved with omeprazole.

The patient’s medications included diclofenac, baclofen, controlled-release morphine sulfate, hydrocodone–acetaminophen, and omeprazole. She had taken oral contraception in the past for extended periods of time. She lived in coastal New England and worked in communications. She drank alcohol occasionally and smoked less than 1 pack of cigarettes per week; she had not smoked during the past few months. She did not use illicit drugs, over-the-counter medications, or herbal medications. There was no family history of bleeding or clotting disorders, spontaneous miscarriage, or hematologic cancer.

On examination, the temperature was 38.3°C, the blood pressure 126/72 mm Hg, the pulse 54 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. She was in mild distress because of her headache, but she was alert and oriented to time and place. Examination of the neck, heart, lungs, abdomen, skin, and oral mucosa was normal. Left homonymous hemianopia was present; other cranial-nerve functions were normal, although function of the first cranial nerve was not tested. Strength, sensation to light touch, and deep-tendon reflexes of the arms and legs were normal. Finger–nose–finger testing showed no dysmetria. Examination of a peripheral-blood smear showed 0 to 2 schistocytes per high-power field, teardrop and pencil cells, occasional large platelets, and normal-appearing white cells. Urinalysis showed 1+ ketones, 2+ blood, 1+ protein, 1+ urobilinogen, a specific gravity greater than 1.040 (normal range, 1.001 to 1.035), and a pH of 5 (normal range, 5 to 9) by dipstick; microscopic examination of the sediment revealed no red cells and 3 to 5 white cells per high-power field (normal range, 0 to 2). Other laboratory test results are shown in Table 1. The patient was admitted to the intensive care unit of this hospital, and additional imaging studies were obtained.

Dr. Gonzalez: MRI of the head confirmed the infarcts and hemorrhagic conversion that had been seen on CT angiography and venography (Figure 2). A cortical vein was not visible over the lesion, which suggested either cortical-vein thrombosis or secondary compression due to mass effect of the parenchymal lesion. On the second hospital day, transfemoral cerebral angiography (Figure 2) showed multiple cerebral venous thromboses involving the right frontal and parietal cortical veins, with no involvement of the major dural sinuses.

Dr. McGrath: A diagnostic test was performed, and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Cerebral Venous Thrombosis (CVT)\n\nThe patient's symptoms of severe headache, loss of peripheral vision, and imaging studies showing multiple cerebral venous thromboses are indicative of CVT. The patient's recent pregnancy termination with methotrexate and use of oral contraceptives, both of which can increase the risk of thrombosis, further support this diagnosis. Additionally, the patient's history of self-limited thrombocytopenia could also contribute to a hypercoagulable state, increasing the risk of CVT.""
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        ""content"": ""The patient's symptoms of severe headache and loss of peripheral vision, along with the imaging findings of cerebral venous thromboses, suggest a diagnosis of cerebral venous sinus thrombosis (CVST). The patient's recent history of pregnancy termination with methotrexate, use of oral contraceptives, and presence of an intrauterine device could all have contributed to a hypercoagulable state, increasing her risk for CVST. Additionally, the patient's history of self-limited thrombocytopenia could suggest an underlying hematologic disorder that could also predispose to thrombosis. The patient's abdominal pain and the imaging finding of splenic vein thrombosis further support a diagnosis of a thrombotic disorder. \n\nDiagnosis: Cerebral venous sinus thrombosis.""
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        ""content"": ""The patient is a 32-year-old woman who presents with severe headache, loss of peripheral vision, and a history of thrombocytopenia. She also has a history of chronic back pain, a vertebral disk herniation, and a recent elective termination of pregnancy with methotrexate. The differential diagnosis for this patient includes cerebral venous thrombosis, migraine, intracranial hemorrhage, and preeclampsia. The patient's symptoms of severe headache and loss of peripheral vision, along with her history of thrombocytopenia, make cerebral venous thrombosis a likely diagnosis. This is further supported by the imaging studies, which show multiple cerebral venous thromboses. Migraine is less likely given the severity of the patient's symptoms and the imaging findings. Intracranial hemorrhage is also less likely given the patient's history and the lack of evidence of bleeding on imaging. Preeclampsia is unlikely given the patient's recent termination of pregnancy and the lack of other symptoms such as high blood pressure and proteinuria. \n\nDiagnosis: Cerebral venous thrombosis.""
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}",Cerebral Venous Thrombosis (CVT),N
10.1056/NEJMcpc1707558,Case 39-2017 — A 41-Year-Old Woman with Recurrent Chest Pain,,Spontaneous coronary-artery dissection.,Spontaneous coronary-artery dissection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:            A 41-year-old woman presented to this hospital with chest pain.

Approximately 1 year before presentation, the patient had had transient tightness in the chest and shoulder on the left side that had prompted a referral to outpatient physical therapy. Five days before presentation, while the patient was packing for a flight to Boston, acute substernal chest pain developed; the pain radiated to the jaw and shoulders and was accompanied by dyspnea and by a feeling of needing to belch. These symptoms lasted 1 hour and then spontaneously resolved, and she attributed them to fatigue.

On the day before presentation, substernal chest pain with radiation to the jaw and shoulders recurred after the patient had been walking, and the pain gradually resolved after a few hours. Before dinner on the evening of presentation, the pain recurred and was associated with light-headedness. The patient attended dinner but had persistent pain, along with dyspnea. She presented to the emergency department of this hospital.

Table 1.

Laboratory Data.
On physical examination, the patient was diaphoretic. The temperature was 36.6°C, the heart rate 68 beats per minute, the blood pressure 143/87 mm Hg in both arms, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. She did not have carotid bruits or jugular venous distention, nor did she have cardiac murmur, rub, or gallop on auscultation. Her digits were hyperextensible. The rest of the examination was normal. Laboratory test results are shown in Table 1.

The patient had no history of dysrhythmia, heart-failure symptoms, trauma, or constitutional, respiratory, gastrointestinal, or neurologic symptoms. She had undergone a laparoscopy for an ovarian cyst, and she had had a miscarriage 1 month before this evaluation. She took no medications. Penicillin and sulfa drugs caused urticaria. She exercised four times weekly with an elliptical machine and walked her dog daily. She did not smoke tobacco or use illicit drugs; she consumed two alcoholic beverages per week. She had a healthy 11-year-old daughter. Her father had a history of hypertension, atrial fibrillation, and an embolic stroke. Her mother, brother, and sister had hypermobile Ehlers–Danlos syndrome: her mother had joint hypermobility and had received the diagnosis during her first pregnancy because of recurrent hip subluxations; her brother had joint hypermobility and spontaneous pneumothorax and bruised easily; and her sister had joint hypermobility and bruised easily. A maternal second cousin had died at 51 years of age from a cerebral aneurysm. Electrocardiography and cardiac imaging studies were performed.

Figure 1.

Electrocardiogram.
Dr. Lucy M. Safi: Electrocardiography showed normal sinus rhythm and submillimeter downsloping ST-segment depressions in leads V3, V4, and V5 (Figure 1). The depressions had decreased in magnitude on electrocardiography performed 3 hours later and had fully resolved on electrocardiography performed 8 hours after presentation.

Transthoracic echocardiography showed overall normal left ventricular and right ventricular systolic function. There was a small, focal area of hypokinesis in the left ventricular inferolateral wall (see Video 1 and Video 2, available with the full text of this article at NEJM.org). There was no clinically significant valvular stenosis, regurgitation, or pericardial effusion. Although there was increased mobility of the interatrial septum, a color Doppler study showed no evidence of a patent foramen ovale.

Dr. Brian B. Ghoshhajra: Posteroanterior and lateral chest radiography showed no abnormalities. Computed tomographic (CT) angiography of the chest was performed after the administration of intravenous contrast material with the use of a standard aortic-dissection protocol. There was no evidence of aortic dissection or proximal pulmonary embolism. The aorta appeared normal, with a preserved sinotubular junction, and the ascending aorta and descending aorta each had a normal diameter. There were no other obvious cardiovascular abnormalities, such as aortic or coronary atherosclerosis, cardiomegaly, or pulmonary edema.

Dr. Vidula: Aspirin, atorvastatin, and intravenous heparin were administered. Diagnostic tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:           A 41-year-old woman presented to this hospital with chest pain.

Approximately 1 year before presentation, the patient had had transient tightness in the chest and shoulder on the left side that had prompted a referral to outpatient physical therapy. Five days before presentation, while the patient was packing for a flight to Boston, acute substernal chest pain developed; the pain radiated to the jaw and shoulders and was accompanied by dyspnea and by a feeling of needing to belch. These symptoms lasted 1 hour and then spontaneously resolved, and she attributed them to fatigue.

On the day before presentation, substernal chest pain with radiation to the jaw and shoulders recurred after the patient had been walking, and the pain gradually resolved after a few hours. Before dinner on the evening of presentation, the pain recurred and was associated with light-headedness. The patient attended dinner but had persistent pain, along with dyspnea. She presented to the emergency department of this hospital.

Table 1.

Laboratory Data.
On physical examination, the patient was diaphoretic. The temperature was 36.6°C, the heart rate 68 beats per minute, the blood pressure 143/87 mm Hg in both arms, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. She did not have carotid bruits or jugular venous distention, nor did she have cardiac murmur, rub, or gallop on auscultation. Her digits were hyperextensible. The rest of the examination was normal. Laboratory test results are shown in Table 1.

The patient had no history of dysrhythmia, heart-failure symptoms, trauma, or constitutional, respiratory, gastrointestinal, or neurologic symptoms. She had undergone a laparoscopy for an ovarian cyst, and she had had a miscarriage 1 month before this evaluation. She took no medications. Penicillin and sulfa drugs caused urticaria. She exercised four times weekly with an elliptical machine and walked her dog daily. She did not smoke tobacco or use illicit drugs; she consumed two alcoholic beverages per week. She had a healthy 11-year-old daughter. Her father had a history of hypertension, atrial fibrillation, and an embolic stroke. Her mother, brother, and sister had hypermobile Ehlers–Danlos syndrome: her mother had joint hypermobility and had received the diagnosis during her first pregnancy because of recurrent hip subluxations; her brother had joint hypermobility and spontaneous pneumothorax and bruised easily; and her sister had joint hypermobility and bruised easily. A maternal second cousin had died at 51 years of age from a cerebral aneurysm. Electrocardiography and cardiac imaging studies were performed.

Figure 1.

Electrocardiogram.
Dr. Lucy M. Safi: Electrocardiography showed normal sinus rhythm and submillimeter downsloping ST-segment depressions in leads V3, V4, and V5 (Figure 1). The depressions had decreased in magnitude on electrocardiography performed 3 hours later and had fully resolved on electrocardiography performed 8 hours after presentation.

Transthoracic echocardiography showed overall normal left ventricular and right ventricular systolic function. There was a small, focal area of hypokinesis in the left ventricular inferolateral wall (see Video 1 and Video 2, available with the full text of this article at NEJM.org). There was no clinically significant valvular stenosis, regurgitation, or pericardial effusion. Although there was increased mobility of the interatrial septum, a color Doppler study showed no evidence of a patent foramen ovale.

Dr. Brian B. Ghoshhajra: Posteroanterior and lateral chest radiography showed no abnormalities. Computed tomographic (CT) angiography of the chest was performed after the administration of intravenous contrast material with the use of a standard aortic-dissection protocol. There was no evidence of aortic dissection or proximal pulmonary embolism. The aorta appeared normal, with a preserved sinotubular junction, and the ascending aorta and descending aorta each had a normal diameter. There were no other obvious cardiovascular abnormalities, such as aortic or coronary atherosclerosis, cardiomegaly, or pulmonary edema.

Dr. Vidula: Aspirin, atorvastatin, and intravenous heparin were administered. Diagnostic tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Spontaneous Coronary Artery Dissection (SCAD)\n\nThe patient's symptoms of chest pain, dyspnea, and lightheadedness are indicative of a cardiac event. The electrocardiogram showed ST-segment depressions, which are often associated with myocardial ischemia. The echocardiogram showed a small, focal area of hypokinesis in the left ventricular inferolateral wall, which suggests a localized area of decreased cardiac muscle movement, often due to a lack of blood supply. The patient's family history of hypermobile Ehlers\u2013Danlos syndrome, a connective tissue disorder, could potentially predispose her to vascular complications such as SCAD. The CT angiography ruled out aortic dissection or proximal pulmonary embolism, but did not rule out SCAD. The administration of aspirin, atorvastatin, and intravenous heparin are consistent with the treatment of an acute coronary syndrome, which can be caused by SCAD.""
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        ""content"": ""The patient's presentation of chest pain radiating to the jaw and shoulders, along with dyspnea and lightheadedness, is suggestive of a cardiac event. However, her EKG showed only submillimeter downsloping ST-segment depressions in leads V3, V4, and V5, which resolved over time. Her echocardiogram showed overall normal left ventricular and right ventricular systolic function with a small, focal area of hypokinesis in the left ventricular inferolateral wall. CT angiography of the chest showed no evidence of aortic dissection or proximal pulmonary embolism. The patient's family history of hypermobile Ehlers-Danlos syndrome, a connective tissue disorder that can affect the blood vessels, is also significant. Given these findings, the most likely diagnosis is spontaneous coronary artery dissection (SCAD), a condition that can occur in patients with connective tissue disorders and can cause symptoms similar to those of a heart attack. \n\nDiagnosis: Spontaneous Coronary Artery Dissection (SCAD)""
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        ""content"": ""The patient is a 41-year-old woman presenting with recurrent chest pain that radiates to the jaw and shoulders, accompanied by dyspnea and lightheadedness. The differential diagnosis for this patient includes myocardial infarction, angina, aortic dissection, and pulmonary embolism. The patient's EKG showed ST-segment depressions in leads V3, V4, and V5, which could suggest ischemia. However, these changes resolved over time, which is not typical for myocardial infarction. Transthoracic echocardiography showed a small, focal area of hypokinesis in the left ventricular inferolateral wall, which could suggest a myocardial infarction or angina. However, the patient's CT angiography did not show any evidence of aortic dissection or proximal pulmonary embolism, and the aorta appeared normal. The patient's family history of hypermobile Ehlers-Danlos syndrome, a connective tissue disorder that can affect the blood vessels, could potentially increase her risk for vascular complications. However, the patient herself did not have any symptoms of this syndrome. Given the patient's symptoms, the findings on EKG and echocardiography, and the lack of findings on CT angiography, the most likely diagnosis is angina.\n\nDiagnosis: Angina""
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10.1056/NEJMcpc1706109,Case 38-2017 — A 20-Year-Old Woman with Seizures and Progressive Dystonia,,Biotin–thiamine–responsive basal ganglia disease due to a homozygous c.1264A_G (p.Thr422Ala) mutation in SLC19A3.,Biotin–thiamine–responsive basal ganglia disease due to a mutation in SLC19A3.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:      A 20-year-old woman was seen in the neurology clinic of this hospital because of seizures and progressive dystonia.

The patient had been well until she was 3 years of age, when she began to have recurrent falls, difficulty walking, and seizures. A diagnostic evaluation at another hospital included a muscle biopsy, electroencephalography, and electroretinography, as well as analysis of the carnitine profile, visual-evoked potentials, and the enzymatic activity of the mitochondrial respiratory chain; the test results were reportedly interpreted as inconclusive. Magnetic resonance imaging (MRI) of the head was performed; T2-weighted images reportedly showed areas of abnormal hyperintensity in the basal ganglia bilaterally. Therapy with carbamazepine and a multivitamin was initiated. During the next 15 years, progressive stepwise deterioration, including worsening dystonia and dysarthria, occurred; cognitive function was not affected. Exacerbations of her neurologic decline were precipitated by acute intercurrent illnesses and recurrent seizures from which she did not have complete recovery.

Five years before the current presentation, anticonvulsant medications were stopped for 1 month. During that period, three flurries of generalized tonic–clonic seizures occurred. During admission to a second hospital, the complete blood count, oxygen saturation, blood levels of calcium and magnesium, and results of liver- and renal-function tests were normal. Medications on discharge included carbamazepine, l-carnitine, coenzyme Q10, and vitamin B complex. On follow-up at that hospital 2 months later, the patient reportedly had dysarthria, dystonic posturing of both arms (especially the hands), and an ataxic gait. Strength was 3+/5 in the distal arms and 5/5 in the proximal arms. Approximately 2.8 years before the current presentation, the patient was evaluated at a third hospital. MRI of the head was performed; T2-weighted and fluid-attenuated inversion recovery (FLAIR) images again showed areas of abnormal hyperintensity in the basal ganglia bilaterally, with mild associated volume loss. The MRI was significantly degraded by susceptibility artifacts that were produced by orthodontic braces. The blood lactate level was 1.6 mmol per liter (14.4 mg per deciliter; reference range at this hospital, 0.5 to 2.2 mmol per liter [4.5 to 19.8 mg per deciliter]), and the cerebrospinal fluid (CSF) lactate level was 1.2 mmol per liter (10.8 mg per deciliter; reference range at this hospital, 0.6 to 2.2 mmol per liter [5.4 to 19.8 mg per deciliter]). A preliminary diagnosis of mitochondrial cytopathy was made.

Between 17 and 11 months before the current presentation, examinations were performed at the second hospital while the patient was receiving levetiracetam and trihexyphenidyl. Speech difficulties, limb rigidity, and spasticity of the left upper leg were noted. She was referred to the epilepsy clinic of this hospital.

On presentation to this hospital, the patient reported dysarthric speech and painful dystonia of her hands and limbs (particularly her legs). The dystonia was associated with gait deterioration that had led to use of a wheelchair. Cognitive function was not affected. Her most recent seizure had occurred 1 year before this assessment.

The patient was the fourth child of healthy consanguineous parents (first cousins). She had been born after a full-term gestation, with no complications. Her birth weight was 3750 g. Medications were levetiracetam, pyridoxine, thiamine, and trihexyphenidyl. She had no known allergies. She lived with her family in the Arabian Peninsula; she spoke Arabic and some English, attended a regular high school, and did not drink alcohol, smoke tobacco, or use illicit drugs. She had three older brothers who were healthy. She had a 6-year-old sister with a similar illness that had started when she was 3 years of age, when she had an episode of bloody diarrhea and then began to have dystonia of the right foot, difficulty walking, and seizures. On evaluation at that time, the sister had a peak blood lactate level of 11.7 mmol per liter (105.4 mg per deciliter) and a peak CSF lactate level of 2.3 mmol per liter (20.7 mg per deciliter). Genetic testing for the MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) and the Leigh syndrome was reportedly negative, and levels of urinary organic acids were normal. The sister underwent MRI of the head during the acute phase of her disease. T2-weighted images showed nonenhancing areas of abnormal, diffuse hyperintensity in the cerebral cortex, basal ganglia, thalami, midbrain, and cerebellum. Repeat imaging studies obtained 10 months later showed resolution of most of the signal abnormalities, although residual signal abnormalities and volume loss were present in the basal ganglia.

On examination at this hospital, which was performed with the assistance of an interpreter, the patient was alert and her mental status was normal. She had severe dysarthria, but her speech was fluent, with no paraphasic errors. Cranial-nerve function was intact, and visual acuity was 20/30 in both eyes. She had fluctuating dystonia of the hands, arms, legs, and feet that was more prominent on the left side than on the right side. Strength was normal throughout. The plantar reflex was extensor in the left foot and was mute in the right foot; deep-tendon reflexes were normal. The gait was slow, wide-based, and dystonic, with inversion and internal rotation of both feet. The remainder of the examination was normal.

MRI of the head was performed without the administration of intravenous contrast material. T2-weighted images showed persistent areas of abnormal hyperintensity, volume loss, and subtle abnormal mineralization in the basal ganglia bilaterally. Electroencephalography, which was performed while the patient was awake and while she was asleep, revealed excessive, diffuse beta activity, with no definitive evidence of epileptiform abnormalities.

The younger sister was present during the clinic visit and was also examined. She had mild dystonia of the right foot, an extensor plantar reflex in the right foot, and a clumsy gait.

Dr. Ann L. Hunt: The patient was referred to the movement disorders clinic of this hospital (see Video 1, available with the full text of this article at NEJM.org). She came to the visit in a wheelchair. Her speech was dysarthric in both English and Arabic. She had previously been a fluent Arabic speaker. While the patient was sitting quietly, she had dystonic posturing of the left hand and both feet. During any activation procedure, the dystonic posturing of the left hand and left foot increased. During rapid successive movements, slowness and dystonic posturing were more prominent in the left hand and foot than in the right hand and foot. There was no rigidity of the arms or legs. When she walked, dystonic posturing was more prominent in the left hand and foot than in the right hand and foot. A pull test revealed good postural stability.

A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:            A 20-year-old woman was seen in the neurology clinic of this hospital because of seizures and progressive dystonia.

The patient had been well until she was 3 years of age, when she began to have recurrent falls, difficulty walking, and seizures. A diagnostic evaluation at another hospital included a muscle biopsy, electroencephalography, and electroretinography, as well as analysis of the carnitine profile, visual-evoked potentials, and the enzymatic activity of the mitochondrial respiratory chain; the test results were reportedly interpreted as inconclusive. Magnetic resonance imaging (MRI) of the head was performed; T2-weighted images reportedly showed areas of abnormal hyperintensity in the basal ganglia bilaterally. Therapy with carbamazepine and a multivitamin was initiated. During the next 15 years, progressive stepwise deterioration, including worsening dystonia and dysarthria, occurred; cognitive function was not affected. Exacerbations of her neurologic decline were precipitated by acute intercurrent illnesses and recurrent seizures from which she did not have complete recovery.

Five years before the current presentation, anticonvulsant medications were stopped for 1 month. During that period, three flurries of generalized tonic–clonic seizures occurred. During admission to a second hospital, the complete blood count, oxygen saturation, blood levels of calcium and magnesium, and results of liver- and renal-function tests were normal. Medications on discharge included carbamazepine, l-carnitine, coenzyme Q10, and vitamin B complex. On follow-up at that hospital 2 months later, the patient reportedly had dysarthria, dystonic posturing of both arms (especially the hands), and an ataxic gait. Strength was 3+/5 in the distal arms and 5/5 in the proximal arms. Approximately 2.8 years before the current presentation, the patient was evaluated at a third hospital. MRI of the head was performed; T2-weighted and fluid-attenuated inversion recovery (FLAIR) images again showed areas of abnormal hyperintensity in the basal ganglia bilaterally, with mild associated volume loss. The MRI was significantly degraded by susceptibility artifacts that were produced by orthodontic braces. The blood lactate level was 1.6 mmol per liter (14.4 mg per deciliter; reference range at this hospital, 0.5 to 2.2 mmol per liter [4.5 to 19.8 mg per deciliter]), and the cerebrospinal fluid (CSF) lactate level was 1.2 mmol per liter (10.8 mg per deciliter; reference range at this hospital, 0.6 to 2.2 mmol per liter [5.4 to 19.8 mg per deciliter]). A preliminary diagnosis of mitochondrial cytopathy was made.

Between 17 and 11 months before the current presentation, examinations were performed at the second hospital while the patient was receiving levetiracetam and trihexyphenidyl. Speech difficulties, limb rigidity, and spasticity of the left upper leg were noted. She was referred to the epilepsy clinic of this hospital.

On presentation to this hospital, the patient reported dysarthric speech and painful dystonia of her hands and limbs (particularly her legs). The dystonia was associated with gait deterioration that had led to use of a wheelchair. Cognitive function was not affected. Her most recent seizure had occurred 1 year before this assessment.

The patient was the fourth child of healthy consanguineous parents (first cousins). She had been born after a full-term gestation, with no complications. Her birth weight was 3750 g. Medications were levetiracetam, pyridoxine, thiamine, and trihexyphenidyl. She had no known allergies. She lived with her family in the Arabian Peninsula; she spoke Arabic and some English, attended a regular high school, and did not drink alcohol, smoke tobacco, or use illicit drugs. She had three older brothers who were healthy. She had a 6-year-old sister with a similar illness that had started when she was 3 years of age, when she had an episode of bloody diarrhea and then began to have dystonia of the right foot, difficulty walking, and seizures. On evaluation at that time, the sister had a peak blood lactate level of 11.7 mmol per liter (105.4 mg per deciliter) and a peak CSF lactate level of 2.3 mmol per liter (20.7 mg per deciliter). Genetic testing for the MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) and the Leigh syndrome was reportedly negative, and levels of urinary organic acids were normal. The sister underwent MRI of the head during the acute phase of her disease. T2-weighted images showed nonenhancing areas of abnormal, diffuse hyperintensity in the cerebral cortex, basal ganglia, thalami, midbrain, and cerebellum. Repeat imaging studies obtained 10 months later showed resolution of most of the signal abnormalities, although residual signal abnormalities and volume loss were present in the basal ganglia.

On examination at this hospital, which was performed with the assistance of an interpreter, the patient was alert and her mental status was normal. She had severe dysarthria, but her speech was fluent, with no paraphasic errors. Cranial-nerve function was intact, and visual acuity was 20/30 in both eyes. She had fluctuating dystonia of the hands, arms, legs, and feet that was more prominent on the left side than on the right side. Strength was normal throughout. The plantar reflex was extensor in the left foot and was mute in the right foot; deep-tendon reflexes were normal. The gait was slow, wide-based, and dystonic, with inversion and internal rotation of both feet. The remainder of the examination was normal.

MRI of the head was performed without the administration of intravenous contrast material. T2-weighted images showed persistent areas of abnormal hyperintensity, volume loss, and subtle abnormal mineralization in the basal ganglia bilaterally. Electroencephalography, which was performed while the patient was awake and while she was asleep, revealed excessive, diffuse beta activity, with no definitive evidence of epileptiform abnormalities.

The younger sister was present during the clinic visit and was also examined. She had mild dystonia of the right foot, an extensor plantar reflex in the right foot, and a clumsy gait.

Dr. Ann L. Hunt: The patient was referred to the movement disorders clinic of this hospital (see Video 1, available with the full text of this article at NEJM.org). She came to the visit in a wheelchair. Her speech was dysarthric in both English and Arabic. She had previously been a fluent Arabic speaker. While the patient was sitting quietly, she had dystonic posturing of the left hand and both feet. During any activation procedure, the dystonic posturing of the left hand and left foot increased. During rapid successive movements, slowness and dystonic posturing were more prominent in the left hand and foot than in the right hand and foot. There was no rigidity of the arms or legs. When she walked, dystonic posturing was more prominent in the left hand and foot than in the right hand and foot. A pull test revealed good postural stability.

A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of seizures, difficulty walking, and progressive dystonia. MRI scans show abnormal hyperintensity in the basal ganglia bilaterally. The patient's younger sister has a similar illness. The symptoms and MRI findings suggest a neurodegenerative disorder. The fact that the patient's sister has a similar illness suggests a genetic disorder. The consanguinity of the parents further supports a genetic disorder. The negative genetic testing for MELAS and Leigh syndrome, common mitochondrial disorders, suggests a less common genetic disorder. The normal lactate levels argue against a mitochondrial disorder. The dystonia, MRI findings, and family history are consistent with a diagnosis of neurodegeneration with brain iron accumulation (NBIA).\n\nDiagnosis: Neurodegeneration with brain iron accumulation (NBIA)""
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        ""content"": ""The patient is a 20-year-old woman with a history of seizures and progressive dystonia since the age of 3. She has a history of recurrent falls, difficulty walking, and seizures. Her symptoms have progressively worsened over the years, with exacerbations during acute illnesses and seizures. Her cognitive function has remained intact. She has a younger sister with a similar illness. The patient's symptoms and family history suggest a genetic or metabolic disorder. The differential diagnosis includes mitochondrial disorders, Wilson's disease, and neurodegenerative disorders. The patient's MRI findings of abnormal hyperintensity in the basal ganglia bilaterally are consistent with a metabolic disorder. The patient's blood and CSF lactate levels were within normal limits, which makes a mitochondrial disorder less likely. Wilson's disease typically presents with liver disease, which the patient does not have, making it less likely. The patient's symptoms have been progressive and have not improved, which is consistent with a neurodegenerative disorder. Given the patient's symptoms, MRI findings, and family history, a neurodegenerative disorder is the most likely diagnosis.\n\nDiagnosis: Neurodegenerative disorder.""
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10.1056/NEJMcpc1710563,Case 37-2017 — A 36-Year-Old Man with Unintentional Opioid Overdose,,"Unintentional opioid overdose, possibly from heroin mixed with fentanyl.

Opioid-induced noncardiogenic pulmonary edema.",Opioid-induced noncardiogenic pulmonary edema.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:          A 36-year-old man with opioid-use disorder was seen in the emergency department of this hospital during the winter because of opioid overdose.

Approximately 4 years before this evaluation, the patient had undergone an unspecified hand surgery. Immediately after the procedure, hydromorphone was administered. After the patient was discharged home, he initially sought out more prescription opioids and then switched to intravenous heroin because he found it to be less expensive and more easily obtained. During the next 3 years, he injected 1 to 2 g of heroin each day.

One year before this evaluation, after the patient lost his job, he attempted to quit using heroin. He began to take methadone, which helped to reduce withdrawal symptoms and cravings, but he stopped taking it after 10 days because he was concerned that weaning off methadone after a period of maintenance treatment would be associated with unacceptable adverse effects. He then resumed heroin use. Six months before this evaluation, the patient again stopped using heroin and was admitted to an inpatient, medically supervised detoxification program for management of withdrawal symptoms. After 2 weeks, he was discharged home.

Approximately 2 months before this evaluation, the patient was released from jail and was admitted to a structured residential rehabilitation program, in which he participated in work therapy, attended regular Narcotics Anonymous meetings, and underwent random, intermittent urine toxicology screenings. He continued in this program and abstained from opioid use until 3 days before this evaluation, when he resumed intravenous heroin use. He obtained the drug, which he believed to be mixed with fentanyl, from a single dealer and began to inject 0.5 g at a time using clean needles and cotton filters. On the day of this evaluation, the patient injected 0.5 g at 10 a.m., followed by another 0.5 g at approximately 1:30 p.m.; he remembered subsequently walking around a park and placing a phone call to a friend to arrange a meeting.

At 2:44 p.m. on the day of this evaluation, emergency medical services personnel were dispatched to the park, where the patient was found lying on the ground in a puddle of slush. He was unresponsive. The patient’s friend was present and reported that when he had found the patient, he had administered intranasal naloxone and then called for emergency medical assistance. First responders from the fire department had administered a second dose of intranasal naloxone before emergency medical services personnel arrived. On examination, the patient appeared cyanotic, and he had a Glasgow Coma Scale score of 3 (on a scale ranging from 3 to 15, with lower scores indicating lower levels of consciousness). The temperature was 35.6°C, the pulse 88 beats per minute, the blood pressure 122/76 mm Hg, the respiratory rate 4 breaths per minute, and the oxygen saturation 80% while he was breathing ambient air. He had pinpoint pupils and shallow breathing. An oropharyngeal airway was placed, and positive-pressure ventilation was initiated with the use of a bag–valve–mask device. The blood glucose level, obtained by fingerstick testing, was 164 mg per deciliter (9.1 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). Several minutes later, the patient woke up, removed the oropharyngeal airway, and was noted to be alert and oriented, with a respiratory rate of 16 breaths per minute. Oxygen was administered through a nasal cannula at a rate of 6 liters per minute, and the patient was transported by ambulance to the emergency department of this hospital.

In the emergency department, the patient reported that the overdose was unintentional, that he had never had an overdose before, that this incident was a “wake-up call,” and that he wanted help with managing his opioid addiction. He had been feeling sad after the recent deaths of his mother and grandmother, and he thought that his relapse in opioid use might have been related to these stressors. He had no history of other medical conditions, took no medications, and had no known allergies. He was a high-school graduate and had worked as an electrician before he became unemployed. He was single and had no children. He had smoked a half-pack of cigarettes daily for the past 4 years and had smoked marijuana when he was younger. He did not drink alcohol or use illicit drugs other than heroin. There was no family history of depression, bipolar disorder, schizophrenia, dementia, or suicide.

On examination, the patient was alert and fully oriented. His clothes were wet. The temperature was 35.9°C, the pulse 84 beats per minute, the blood pressure 115/69 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 93% while he was breathing oxygen through a nasal cannula at a rate of 6 liters per minute. The pupils were equal, round, and reactive to light. There were scattered focal crackles in the lungs, and the remainder of the examination was normal. The hemoglobin level, hematocrit, white-cell count, differential count, platelet count, and red-cell indexes were normal, as were blood levels of electrolytes, the anion gap, and results of renal-function tests. The blood glucose level was 165 mg per deciliter (9.2 mmol per liter). Venous blood gas measurements, which were obtained while the patient was breathing oxygen through a nasal cannula at a rate of 6 liters per minute, included a pH of 7.29 (reference range, 7.30 to 7.40), a partial pressure of carbon dioxide of 68 mm Hg (reference range, 38 to 50), a partial pressure of oxygen of less than 28 mm Hg (reference range, 35 to 50), a bicarbonate level of 32 mmol per liter (reference range, 24 to 30), and a base excess of 2.6 mmol per liter (reference range, 0 to 3.0). An electrocardiogram showed nonspecific ST-segment and T-wave abnormalities and was otherwise normal.

Figure 1.

Initial Chest Radiograph.
Dr. Efrén J. Flores: A portable anteroposterior radiograph of the chest (Figure 1) revealed cephalization of the pulmonary vasculature and fluid in the minor fissure, findings consistent with interstitial pulmonary edema. There were also bilateral nodular and patchy airspace opacities, findings that suggested superimposed aspiration.

Dr. Martin: A diagnosis and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:            A 36-year-old man with opioid-use disorder was seen in the emergency department of this hospital during the winter because of opioid overdose.

Approximately 4 years before this evaluation, the patient had undergone an unspecified hand surgery. Immediately after the procedure, hydromorphone was administered. After the patient was discharged home, he initially sought out more prescription opioids and then switched to intravenous heroin because he found it to be less expensive and more easily obtained. During the next 3 years, he injected 1 to 2 g of heroin each day.

One year before this evaluation, after the patient lost his job, he attempted to quit using heroin. He began to take methadone, which helped to reduce withdrawal symptoms and cravings, but he stopped taking it after 10 days because he was concerned that weaning off methadone after a period of maintenance treatment would be associated with unacceptable adverse effects. He then resumed heroin use. Six months before this evaluation, the patient again stopped using heroin and was admitted to an inpatient, medically supervised detoxification program for management of withdrawal symptoms. After 2 weeks, he was discharged home.

Approximately 2 months before this evaluation, the patient was released from jail and was admitted to a structured residential rehabilitation program, in which he participated in work therapy, attended regular Narcotics Anonymous meetings, and underwent random, intermittent urine toxicology screenings. He continued in this program and abstained from opioid use until 3 days before this evaluation, when he resumed intravenous heroin use. He obtained the drug, which he believed to be mixed with fentanyl, from a single dealer and began to inject 0.5 g at a time using clean needles and cotton filters. On the day of this evaluation, the patient injected 0.5 g at 10 a.m., followed by another 0.5 g at approximately 1:30 p.m.; he remembered subsequently walking around a park and placing a phone call to a friend to arrange a meeting.

At 2:44 p.m. on the day of this evaluation, emergency medical services personnel were dispatched to the park, where the patient was found lying on the ground in a puddle of slush. He was unresponsive. The patient’s friend was present and reported that when he had found the patient, he had administered intranasal naloxone and then called for emergency medical assistance. First responders from the fire department had administered a second dose of intranasal naloxone before emergency medical services personnel arrived. On examination, the patient appeared cyanotic, and he had a Glasgow Coma Scale score of 3 (on a scale ranging from 3 to 15, with lower scores indicating lower levels of consciousness). The temperature was 35.6°C, the pulse 88 beats per minute, the blood pressure 122/76 mm Hg, the respiratory rate 4 breaths per minute, and the oxygen saturation 80% while he was breathing ambient air. He had pinpoint pupils and shallow breathing. An oropharyngeal airway was placed, and positive-pressure ventilation was initiated with the use of a bag–valve–mask device. The blood glucose level, obtained by fingerstick testing, was 164 mg per deciliter (9.1 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). Several minutes later, the patient woke up, removed the oropharyngeal airway, and was noted to be alert and oriented, with a respiratory rate of 16 breaths per minute. Oxygen was administered through a nasal cannula at a rate of 6 liters per minute, and the patient was transported by ambulance to the emergency department of this hospital.

In the emergency department, the patient reported that the overdose was unintentional, that he had never had an overdose before, that this incident was a “wake-up call,” and that he wanted help with managing his opioid addiction. He had been feeling sad after the recent deaths of his mother and grandmother, and he thought that his relapse in opioid use might have been related to these stressors. He had no history of other medical conditions, took no medications, and had no known allergies. He was a high-school graduate and had worked as an electrician before he became unemployed. He was single and had no children. He had smoked a half-pack of cigarettes daily for the past 4 years and had smoked marijuana when he was younger. He did not drink alcohol or use illicit drugs other than heroin. There was no family history of depression, bipolar disorder, schizophrenia, dementia, or suicide.

On examination, the patient was alert and fully oriented. His clothes were wet. The temperature was 35.9°C, the pulse 84 beats per minute, the blood pressure 115/69 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 93% while he was breathing oxygen through a nasal cannula at a rate of 6 liters per minute. The pupils were equal, round, and reactive to light. There were scattered focal crackles in the lungs, and the remainder of the examination was normal. The hemoglobin level, hematocrit, white-cell count, differential count, platelet count, and red-cell indexes were normal, as were blood levels of electrolytes, the anion gap, and results of renal-function tests. The blood glucose level was 165 mg per deciliter (9.2 mmol per liter). Venous blood gas measurements, which were obtained while the patient was breathing oxygen through a nasal cannula at a rate of 6 liters per minute, included a pH of 7.29 (reference range, 7.30 to 7.40), a partial pressure of carbon dioxide of 68 mm Hg (reference range, 38 to 50), a partial pressure of oxygen of less than 28 mm Hg (reference range, 35 to 50), a bicarbonate level of 32 mmol per liter (reference range, 24 to 30), and a base excess of 2.6 mmol per liter (reference range, 0 to 3.0). An electrocardiogram showed nonspecific ST-segment and T-wave abnormalities and was otherwise normal.

Figure 1.

Initial Chest Radiograph.
Dr. Efrén J. Flores: A portable anteroposterior radiograph of the chest (Figure 1) revealed cephalization of the pulmonary vasculature and fluid in the minor fissure, findings consistent with interstitial pulmonary edema. There were also bilateral nodular and patchy airspace opacities, findings that suggested superimposed aspiration.

Dr. Martin: A diagnosis and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Opioid overdose with aspiration pneumonia and hypothermia. \n\nThe patient's history of opioid use disorder, recent heroin use, and presentation of unresponsiveness, cyanosis, shallow breathing, and pinpoint pupils are all indicative of an opioid overdose. The administration of naloxone by the patient's friend and first responders, and the subsequent improvement in the patient's condition, further supports this diagnosis. The chest radiograph showing bilateral nodular and patchy airspace opacities suggests aspiration, likely due to the patient's decreased level of consciousness during the overdose. The patient's low body temperature on presentation and wet clothes suggest hypothermia, likely due to lying on the ground in a puddle of slush.""
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10.1056/NEJMcpc1710565,"Case 36-2017 — A 30-Year-Old Man with Fatigue, Rash, Anemia, and Thrombocytopenia",,Combined inherited and acquired thrombotic thrombocytopenic purpura.,Thrombotic thrombocytopenic purpura.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 30-year-old man was admitted to this hospital during the summer because of fatigue, rash, fevers, anemia, and thrombocytopenia.

Figure 1.

CT Scans of the Abdomen and Pelvis Obtained 3 Years before Admission.
Table 1.

Laboratory Data.
Three years before this admission, the patient was involved in a motor vehicle accident that resulted in a large hematoma across the chest and umbilicus. He was evaluated at another hospital. Computed tomography (CT) of the head, cervical spine, abdomen, and pelvis, performed with the intravenous administration of contrast material, revealed stranding of the anterior abdominal wall, the subcutaneous tissues of the left flank, and the fat of the left retroperitoneum (Figure 1); this finding was reported to be consistent with soft-tissue contusion or hemorrhage. Laboratory test results are shown in Table 1. The patient was discharged home.

Two days later, gross hematuria developed, and the patient was evaluated at the other hospital; laboratory test results are shown in Table 1. He was transferred to this hospital for evaluation of thrombocytopenia and hematuria.

Dr. Amirkasra Mojtahed: CT of the abdomen and pelvis, performed with and without the intravenous administration of contrast material (in accordance with a hematuria protocol), revealed no renal or ureteral stones, solid renal masses, or ureteral or bladder filling defects. The stranding of the anterior abdominal wall, left flank, and left retroperitoneum appeared to have been stable since the previous study had been obtained, 3 days earlier.

Dr. Yuan: The hematuria resolved without intervention. Examination of a peripheral-blood smear revealed anisocytosis and polychromasia of the red cells, with occasional schistocytes, as well as a reduced number of platelets and normal-appearing white cells. Giemsa staining of thick and thin blood smears revealed no intracellular organisms. Tests for IgG and IgM antibodies to Ehrlichia chaffeensis, Anaplasma phagocytophilum, and Borrelia burgdorferi were negative. The thrombocytopenia and anemia were attributed to large soft-tissue hematomas and hematuria, and the patient was discharged home. On follow-up evaluation 1 week after discharge, the platelet count was 242,000 per cubic millimeter (normal range, 150,000 to 400,000); 1 month after discharge, the hematocrit was 44% (normal range, 41 to 53).

The patient had been in his usual state of health until 2 weeks before the current admission to this hospital, when fatigue, generalized weakness, and dyspnea on exertion developed. Four episodes of palpitations, chest tightness, and diaphoresis occurred during the 2-week period leading up to admission; they lasted less than 1 minute each, and the patient attributed them to panic attacks. Five days before this admission, fevers and night sweats developed, and the highest measured temperature was 38.3°C. Three days before this admission, the patient noted an area of erythema in the posterior aspect of the right knee and bruising on both arms. One day before this admission, an episode of weakness and tunnel vision occurred while the patient was standing; he lowered himself to the ground but did not lose consciousness. Severe fatigue persisted after the episode, and he was evaluated in the emergency department of the other hospital. Laboratory test results are shown in Table 1. Giemsa staining of thick and thin blood smears revealed no intracellular organisms. A screening test for antibodies to B. burgdorferi was positive. Doxycycline, clindamycin, and quinine were administered, and the patient was transferred to the emergency department of this hospital.

On evaluation in the emergency department, the patient reported a mild headache, which diminished after the administration of ibuprofen; there was no neck pain or photophobia. He had a history of alcohol-use disorder, peptic ulcer disease, Barrett’s esophagus, and anxiety. He had no history of easy bruising or bleeding, despite previous trauma, including a fall from a roof 3 years before admission. Recent medications included diazepam and citalopram. He drank alcohol occasionally in a binge pattern but had not had any during the past 2 weeks. He did not smoke cigarettes, use illicit drugs, or take herbal medications. He resided on an island in New England and worked as a restaurant cook. He noted ticks on his body several times per month and had removed a tick 2 weeks before this presentation. His mother had diabetes, and his father had hypertension. There was no family history of hematologic cancer.

Figure 2.

Clinical Photograph and Peripheral-Blood Specimen Obtained on Admission.
On examination, the temperature was 36.6°C, the blood pressure 112/57 mm Hg, the pulse 88 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. He was alert and oriented and did not appear ill. The first and second heart sounds were normal, and the lungs were clear. The abdomen was not distended; bowel sounds were present, with no tenderness on palpation or hepatosplenomegaly. There was no swelling in the legs. An area of blanching erythema (6 cm in diameter) was present on the right popliteal fossa (Figure 2A); a similar lesion (5 cm in diameter) was present near the left patella. Areas of petechiae were noted in the erythematous lesions and on the left flank.

Examination of a peripheral-blood smear (Figure 2B) revealed mostly normocytic erythrocytes, with less than 1 schistocyte per high-power field (i.e., occasional schistocytes were seen, but not in every high-power field), increased reticulocytes, no spherocytes, minor basophilic stippling, and no inclusion bodies in erythrocytes. Platelets were decreased in number but increased in size and had normal granularity. White cells appeared normal and had a normal granulation pattern. Giemsa staining of thick and thin blood smears revealed no intracellular organisms. Tests for human immunodeficiency virus (HIV) p24 antigen and HIV type 1 and type 2 antibodies were negative. Urinalysis showed 2+ blood and 2+ protein, with no glucose, ketones, bilirubin, urobilinogen, or nitrates; the specific gravity and pH were normal, and examination of the sediment revealed 20 to 50 red cells per high-power field (normal range, 0 to 2). Other laboratory test results are shown in Table 1. Two units of packed red cells were transfused; the hematocrit increased from 17.6% on admission to 22.5% (normal range, 41 to 53), and the patient was admitted to the hospital. Azithromycin and atovaquone were administered, and doxycycline was continued.

On the third hospital day, the patient had the sudden onset of expressive aphasia, pronator drift of the right arm, and inability to follow complex commands. The remainder of the neurologic examination was normal. Laboratory test results are shown in Table 1.

Dr. Mojtahed: CT angiography of the head and neck revealed normal intracranial and neck vessels. There was no evidence of intracranial hemorrhage, acute infarction, or intracranial lesions.

Dr. Yuan: A diagnostic test was performed, and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  A 30-year-old man was admitted to this hospital during the summer because of fatigue, rash, fevers, anemia, and thrombocytopenia.

Figure 1.

CT Scans of the Abdomen and Pelvis Obtained 3 Years before Admission.
Table 1.

Laboratory Data.
Three years before this admission, the patient was involved in a motor vehicle accident that resulted in a large hematoma across the chest and umbilicus. He was evaluated at another hospital. Computed tomography (CT) of the head, cervical spine, abdomen, and pelvis, performed with the intravenous administration of contrast material, revealed stranding of the anterior abdominal wall, the subcutaneous tissues of the left flank, and the fat of the left retroperitoneum (Figure 1); this finding was reported to be consistent with soft-tissue contusion or hemorrhage. Laboratory test results are shown in Table 1. The patient was discharged home.

Two days later, gross hematuria developed, and the patient was evaluated at the other hospital; laboratory test results are shown in Table 1. He was transferred to this hospital for evaluation of thrombocytopenia and hematuria.

Dr. Amirkasra Mojtahed: CT of the abdomen and pelvis, performed with and without the intravenous administration of contrast material (in accordance with a hematuria protocol), revealed no renal or ureteral stones, solid renal masses, or ureteral or bladder filling defects. The stranding of the anterior abdominal wall, left flank, and left retroperitoneum appeared to have been stable since the previous study had been obtained, 3 days earlier.

Dr. Yuan: The hematuria resolved without intervention. Examination of a peripheral-blood smear revealed anisocytosis and polychromasia of the red cells, with occasional schistocytes, as well as a reduced number of platelets and normal-appearing white cells. Giemsa staining of thick and thin blood smears revealed no intracellular organisms. Tests for IgG and IgM antibodies to Ehrlichia chaffeensis, Anaplasma phagocytophilum, and Borrelia burgdorferi were negative. The thrombocytopenia and anemia were attributed to large soft-tissue hematomas and hematuria, and the patient was discharged home. On follow-up evaluation 1 week after discharge, the platelet count was 242,000 per cubic millimeter (normal range, 150,000 to 400,000); 1 month after discharge, the hematocrit was 44% (normal range, 41 to 53).

The patient had been in his usual state of health until 2 weeks before the current admission to this hospital, when fatigue, generalized weakness, and dyspnea on exertion developed. Four episodes of palpitations, chest tightness, and diaphoresis occurred during the 2-week period leading up to admission; they lasted less than 1 minute each, and the patient attributed them to panic attacks. Five days before this admission, fevers and night sweats developed, and the highest measured temperature was 38.3°C. Three days before this admission, the patient noted an area of erythema in the posterior aspect of the right knee and bruising on both arms. One day before this admission, an episode of weakness and tunnel vision occurred while the patient was standing; he lowered himself to the ground but did not lose consciousness. Severe fatigue persisted after the episode, and he was evaluated in the emergency department of the other hospital. Laboratory test results are shown in Table 1. Giemsa staining of thick and thin blood smears revealed no intracellular organisms. A screening test for antibodies to B. burgdorferi was positive. Doxycycline, clindamycin, and quinine were administered, and the patient was transferred to the emergency department of this hospital.

On evaluation in the emergency department, the patient reported a mild headache, which diminished after the administration of ibuprofen; there was no neck pain or photophobia. He had a history of alcohol-use disorder, peptic ulcer disease, Barrett’s esophagus, and anxiety. He had no history of easy bruising or bleeding, despite previous trauma, including a fall from a roof 3 years before admission. Recent medications included diazepam and citalopram. He drank alcohol occasionally in a binge pattern but had not had any during the past 2 weeks. He did not smoke cigarettes, use illicit drugs, or take herbal medications. He resided on an island in New England and worked as a restaurant cook. He noted ticks on his body several times per month and had removed a tick 2 weeks before this presentation. His mother had diabetes, and his father had hypertension. There was no family history of hematologic cancer.

Figure 2.

Clinical Photograph and Peripheral-Blood Specimen Obtained on Admission.
On examination, the temperature was 36.6°C, the blood pressure 112/57 mm Hg, the pulse 88 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. He was alert and oriented and did not appear ill. The first and second heart sounds were normal, and the lungs were clear. The abdomen was not distended; bowel sounds were present, with no tenderness on palpation or hepatosplenomegaly. There was no swelling in the legs. An area of blanching erythema (6 cm in diameter) was present on the right popliteal fossa (Figure 2A); a similar lesion (5 cm in diameter) was present near the left patella. Areas of petechiae were noted in the erythematous lesions and on the left flank.

Examination of a peripheral-blood smear (Figure 2B) revealed mostly normocytic erythrocytes, with less than 1 schistocyte per high-power field (i.e., occasional schistocytes were seen, but not in every high-power field), increased reticulocytes, no spherocytes, minor basophilic stippling, and no inclusion bodies in erythrocytes. Platelets were decreased in number but increased in size and had normal granularity. White cells appeared normal and had a normal granulation pattern. Giemsa staining of thick and thin blood smears revealed no intracellular organisms. Tests for human immunodeficiency virus (HIV) p24 antigen and HIV type 1 and type 2 antibodies were negative. Urinalysis showed 2+ blood and 2+ protein, with no glucose, ketones, bilirubin, urobilinogen, or nitrates; the specific gravity and pH were normal, and examination of the sediment revealed 20 to 50 red cells per high-power field (normal range, 0 to 2). Other laboratory test results are shown in Table 1. Two units of packed red cells were transfused; the hematocrit increased from 17.6% on admission to 22.5% (normal range, 41 to 53), and the patient was admitted to the hospital. Azithromycin and atovaquone were administered, and doxycycline was continued.

On the third hospital day, the patient had the sudden onset of expressive aphasia, pronator drift of the right arm, and inability to follow complex commands. The remainder of the neurologic examination was normal. Laboratory test results are shown in Table 1.

Dr. Mojtahed: CT angiography of the head and neck revealed normal intracranial and neck vessels. There was no evidence of intracranial hemorrhage, acute infarction, or intracranial lesions.

Dr. Yuan: A diagnostic test was performed, and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Babesiosis. The patient's symptoms of fatigue, rash, fevers, anemia, and thrombocytopenia, along with his history of tick exposure and residence in New England (an area known for tick-borne diseases), suggest a tick-borne illness. The negative tests for Ehrlichia, Anaplasma, and Borrelia burgdorferi (the causative agent of Lyme disease) make these less likely. Babesiosis, another tick-borne disease, can cause the patient's symptoms and is endemic in the New England area. The presence of anisocytosis and polychromasia of the red cells, with occasional schistocytes, as well as a reduced number of platelets and normal-appearing white cells, is consistent with babesiosis, which can cause hemolytic anemia and thrombocytopenia. The absence of intracellular organisms on Giemsa staining does not rule out babesiosis, as the organisms may not always be visible on peripheral smear.""
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        ""content"": ""The patient's symptoms of fatigue, rash, fevers, anemia, and thrombocytopenia, along with a history of tick exposure, suggest a tick-borne illness. The positive screening test for antibodies to B. burgdorferi, the bacterium that causes Lyme disease, supports this diagnosis. However, the patient's severe thrombocytopenia and anemia, along with the sudden onset of neurologic symptoms, suggest a more severe illness. Babesiosis, another tick-borne illness, can cause severe disease, particularly in people with asplenia, and can cause hemolytic anemia and thrombocytopenia. The patient's peripheral blood smear showed no intracellular organisms, which would typically be seen in babesiosis, but the sensitivity of blood smears for detecting Babesia can be low. The patient's symptoms improved with treatment with azithromycin and atovaquone, which are effective against Babesia, further supporting this diagnosis.\n\nDiagnosis: Babesiosis.""
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        ""content"": ""The patient is a 30-year-old man presenting with fatigue, rash, fevers, anemia, and thrombocytopenia. He has a history of alcohol-use disorder, peptic ulcer disease, Barrett\u2019s esophagus, and anxiety. He also has a history of tick exposure, which is significant given his symptoms and location in New England. The differential diagnosis includes Lyme disease, Babesiosis, Anaplasmosis, Ehrlichiosis, and other tick-borne diseases. He also has a positive screening test for antibodies to B. burgdorferi, which is the causative agent of Lyme disease. However, his symptoms of anemia and thrombocytopenia are not typical for Lyme disease. Babesiosis is a tick-borne disease that can cause hemolytic anemia and thrombocytopenia, which fits with the patient's symptoms. The patient's peripheral blood smear does not show the characteristic intraerythrocytic parasites seen in Babesiosis, but this test can be negative in up to 40% of cases. The patient's symptoms of fatigue, fever, and rash, along with his laboratory findings of anemia and thrombocytopenia, are consistent with Babesiosis. \n\nDiagnosis: Babesiosis.""
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10.1056/NEJMcpc1710564,Case 35-2017 — A 57-Year-Old Woman with Hypoesthesia and Weakness in the Legs and Arms,,Copper deficiency myelopathy.,Copper deficiency myelopathy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:           A 57-year-old-woman was admitted to this hospital because of progressive hypoesthesia, paresthesia, and weakness in the arms and legs.

The patient had been in her usual health until 18 months before this admission, when paresthesia developed in the feet. Sixteen months before this admission, the patient underwent lumbar surgery, including laminectomy and facetectomies at L3–L4 and bilateral foraminotomies at L4. After surgery, she reported that the symptoms in the feet had diminished.

Nine months before this admission, hypoesthesia and weakness recurred in the feet; over a period of several months, they spread to involve the legs and hands. The patient had several falls at home and began to use a cane and then a wheelchair. Eight months before this admission, she was evaluated at an outpatient neurology clinic, and electromyography and nerve-conduction studies were performed. A presumptive diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) was made, and intravenous immune globulin (IVIG) was administered; the patient reported transient improvement in sensation and strength in her legs and hands. During the next 6 months, IVIG was administered every 4 weeks, but hypoesthesia and weakness progressed to involve both arms. When she was no longer able to transfer safely into a wheelchair, she presented to the emergency department of another hospital for evaluation.

In the emergency department of the other hospital, the patient reported inconsistent bowel and bladder continence and progressive hypoesthesia and weakness in her legs and arms. She had a history of chronic low-back pain (which had been treated with opioids), fibromyalgia, headaches, and depression. Surgeries included appendectomy, cholecystectomy, and hysterectomy in the distant past, as well as Roux-en-Y gastric bypass approximately 4 years earlier. Medications included controlled-release morphine sulfate, hydrocodone with acetaminophen, gabapentin, diazepam, cyclobenzaprine, valproic acid, citalopram, cyanocobalamin, and cholecalciferol. The patient was married, lived with her husband in New England, and did not smoke tobacco, drink alcohol, or use illicit drugs. There was no family history of autoimmune disease; her father had a history of bladder cancer.

On examination at the other hospital, the temperature was 36.6°C, the blood pressure 138/66 mm Hg, the pulse 64 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The oropharynx had no erythema or exudate; the patient was edentulous, with a normal-appearing oral mucosa and tongue. Results of cranial-nerve examinations were normal (although the first cranial nerve was not tested). Strength was 0–1 out of 5 in the legs and 3 out of 5 in the arms. Sensation to pinprick was decreased in both legs, from the toes to the hips. Negative inspiratory force at functional residual capacity and vital capacity were normal. A stage 2 pressure ulcer was present over the sacrum. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Blood levels of electrolytes, glucose, vitamin B12 (cobalamin), and vitamin B9 (folate) were normal, as were results of kidney- and liver-function tests. Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2 and hepatitis C virus were negative. The blood level of valproic acid was 15.3 _g per milliliter (therapeutic range, 50 to 100). Urinalysis was unremarkable. Other laboratory test results are shown in Table 1. Magnetic resonance imaging (MRI) of the head was performed without the administration of contrast material; T2-weighted images showed mild abnormalities in the periventricular white matter, a finding consistent with a chronic small-vessel ischemic process. Valproic acid was stopped, high-dose methylprednisolone was administered, and the patient was transferred to the neurology department of this hospital for evaluation.

On examination at this hospital, results of a mental-status examination (including tests of language, attention, and memory) were normal. There was no voluntary movement in the legs; there was atrophy of the calf and foot muscles. Weakness was more severe in the hands than in the proximal arms. Deep-tendon reflexes were 2+ at the ankles, 3+ at the patellas, and 3+ at the biceps. Perception of vibration, light touch, and pinprick was absent in the legs and diminished in the arms. Sensation to pinprick was impaired caudal to the T4 level. The plantar reflex was absent bilaterally. A blood test for antinuclear antibodies was positive at a titer of 1:40, with a speckled pattern. Serum protein electrophoresis revealed a normal pattern, with a moderate, diffuse increase in immune globulin. Screening tests for antitreponemal antibodies and for antibodies to Borrelia burgdorferi and human T-lymphotropic virus (HTLV) types 1 and 2 were negative. Other laboratory test results are shown in Table 1. Nerve-conduction studies and needle electromyography were performed.

Dr. William S. David: The nerve-conduction studies revealed normal sensory responses, apart from a mildly reduced amplitude of the right ulnar nerve. Fibular motor responses could not be elicited in the extensor digitorum brevis muscle in either leg; fibular motor responses were severely reduced in the tibialis anterior muscle in both legs, as were posterior tibial motor responses in the abductor hallucis muscle. Distal motor latencies and velocities were normal. Needle electromyography revealed scattered fibrillation potentials and positive sharp waves in two muscles in the right arm and two muscles in the right leg. The patient was unable to activate units in several muscles in the arms and legs. In other muscles, there was a reduced number of normal-appearing motor units and slow firing of those units, findings suggestive of impaired activation.

Dr. Rubin: MRI of the cervical, thoracic, and lumbar spine, performed with and without the administration of intravenous contrast material, revealed mild scattered degenerative changes of the spine, with no evidence of cord compression, nerve-root impingement, or a demyelinating process. A lumbar puncture was performed for analysis of the cerebrospinal fluid (CSF); results are shown in Table 1. Hypoesthesia and weakness in the arms and legs did not improve, and the results of a neurologic examination were unchanged from those obtained on admission.

Dr. David: On the fifth hospital day, studies for somatosensory evoked potentials were performed. The right median somatosensory evoked potential was normal; the left side was not studied. The P37 scalp waveform was absent in the right tibial somatosensory evoked potential, a finding that suggested a disruption of central conduction.

Dr. Rubin: A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:             A 57-year-old-woman was admitted to this hospital because of progressive hypoesthesia, paresthesia, and weakness in the arms and legs.

The patient had been in her usual health until 18 months before this admission, when paresthesia developed in the feet. Sixteen months before this admission, the patient underwent lumbar surgery, including laminectomy and facetectomies at L3–L4 and bilateral foraminotomies at L4. After surgery, she reported that the symptoms in the feet had diminished.

Nine months before this admission, hypoesthesia and weakness recurred in the feet; over a period of several months, they spread to involve the legs and hands. The patient had several falls at home and began to use a cane and then a wheelchair. Eight months before this admission, she was evaluated at an outpatient neurology clinic, and electromyography and nerve-conduction studies were performed. A presumptive diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) was made, and intravenous immune globulin (IVIG) was administered; the patient reported transient improvement in sensation and strength in her legs and hands. During the next 6 months, IVIG was administered every 4 weeks, but hypoesthesia and weakness progressed to involve both arms. When she was no longer able to transfer safely into a wheelchair, she presented to the emergency department of another hospital for evaluation.

In the emergency department of the other hospital, the patient reported inconsistent bowel and bladder continence and progressive hypoesthesia and weakness in her legs and arms. She had a history of chronic low-back pain (which had been treated with opioids), fibromyalgia, headaches, and depression. Surgeries included appendectomy, cholecystectomy, and hysterectomy in the distant past, as well as Roux-en-Y gastric bypass approximately 4 years earlier. Medications included controlled-release morphine sulfate, hydrocodone with acetaminophen, gabapentin, diazepam, cyclobenzaprine, valproic acid, citalopram, cyanocobalamin, and cholecalciferol. The patient was married, lived with her husband in New England, and did not smoke tobacco, drink alcohol, or use illicit drugs. There was no family history of autoimmune disease; her father had a history of bladder cancer.

On examination at the other hospital, the temperature was 36.6°C, the blood pressure 138/66 mm Hg, the pulse 64 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The oropharynx had no erythema or exudate; the patient was edentulous, with a normal-appearing oral mucosa and tongue. Results of cranial-nerve examinations were normal (although the first cranial nerve was not tested). Strength was 0–1 out of 5 in the legs and 3 out of 5 in the arms. Sensation to pinprick was decreased in both legs, from the toes to the hips. Negative inspiratory force at functional residual capacity and vital capacity were normal. A stage 2 pressure ulcer was present over the sacrum. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Blood levels of electrolytes, glucose, vitamin B12 (cobalamin), and vitamin B9 (folate) were normal, as were results of kidney- and liver-function tests. Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen and antibodies to HIV types 1 and 2 and hepatitis C virus were negative. The blood level of valproic acid was 15.3 _g per milliliter (therapeutic range, 50 to 100). Urinalysis was unremarkable. Other laboratory test results are shown in Table 1. Magnetic resonance imaging (MRI) of the head was performed without the administration of contrast material; T2-weighted images showed mild abnormalities in the periventricular white matter, a finding consistent with a chronic small-vessel ischemic process. Valproic acid was stopped, high-dose methylprednisolone was administered, and the patient was transferred to the neurology department of this hospital for evaluation.

On examination at this hospital, results of a mental-status examination (including tests of language, attention, and memory) were normal. There was no voluntary movement in the legs; there was atrophy of the calf and foot muscles. Weakness was more severe in the hands than in the proximal arms. Deep-tendon reflexes were 2+ at the ankles, 3+ at the patellas, and 3+ at the biceps. Perception of vibration, light touch, and pinprick was absent in the legs and diminished in the arms. Sensation to pinprick was impaired caudal to the T4 level. The plantar reflex was absent bilaterally. A blood test for antinuclear antibodies was positive at a titer of 1:40, with a speckled pattern. Serum protein electrophoresis revealed a normal pattern, with a moderate, diffuse increase in immune globulin. Screening tests for antitreponemal antibodies and for antibodies to Borrelia burgdorferi and human T-lymphotropic virus (HTLV) types 1 and 2 were negative. Other laboratory test results are shown in Table 1. Nerve-conduction studies and needle electromyography were performed.

Dr. William S. David: The nerve-conduction studies revealed normal sensory responses, apart from a mildly reduced amplitude of the right ulnar nerve. Fibular motor responses could not be elicited in the extensor digitorum brevis muscle in either leg; fibular motor responses were severely reduced in the tibialis anterior muscle in both legs, as were posterior tibial motor responses in the abductor hallucis muscle. Distal motor latencies and velocities were normal. Needle electromyography revealed scattered fibrillation potentials and positive sharp waves in two muscles in the right arm and two muscles in the right leg. The patient was unable to activate units in several muscles in the arms and legs. In other muscles, there was a reduced number of normal-appearing motor units and slow firing of those units, findings suggestive of impaired activation.

Dr. Rubin: MRI of the cervical, thoracic, and lumbar spine, performed with and without the administration of intravenous contrast material, revealed mild scattered degenerative changes of the spine, with no evidence of cord compression, nerve-root impingement, or a demyelinating process. A lumbar puncture was performed for analysis of the cerebrospinal fluid (CSF); results are shown in Table 1. Hypoesthesia and weakness in the arms and legs did not improve, and the results of a neurologic examination were unchanged from those obtained on admission.

Dr. David: On the fifth hospital day, studies for somatosensory evoked potentials were performed. The right median somatosensory evoked potential was normal; the left side was not studied. The P37 scalp waveform was absent in the right tibial somatosensory evoked potential, a finding that suggested a disruption of central conduction.

Dr. Rubin: A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Subacute combined degeneration of the spinal cord. The patient's history of gastric bypass surgery, combined with her neurological symptoms, suggest a deficiency in vitamin B12 absorption, which can lead to this condition. Despite normal serum B12 levels, the patient may still be functionally deficient. The MRI findings of periventricular white matter changes are also consistent with this diagnosis.""
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        ""content"": ""The patient's symptoms of progressive hypoesthesia, paresthesia, and weakness in the arms and legs, along with the negative results for infectious diseases and the positive antinuclear antibodies test, suggest an autoimmune disease. The patient's history of chronic low-back pain and fibromyalgia, as well as the results of the nerve-conduction studies and needle electromyography, further support this. The absence of the P37 scalp waveform in the right tibial somatosensory evoked potential suggests a disruption of central conduction, which is consistent with a demyelinating disease. The patient's symptoms and test results do not improve with treatment for chronic inflammatory demyelinating polyneuropathy (CIDP), suggesting that this is not the correct diagnosis. Given these findings, the most likely diagnosis is a form of autoimmune demyelinating disease.\n\nDiagnosis: Autoimmune Demyelinating Disease""
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        ""content"": ""The patient is a 57-year-old woman with a history of chronic low-back pain, fibromyalgia, headaches, and depression. She presents with progressive hypoesthesia, paresthesia, and weakness in the arms and legs. The differential diagnosis for this patient includes chronic inflammatory demyelinating polyneuropathy (CIDP), multiple sclerosis, Guillain-Barre syndrome, and vitamin B12 deficiency. The patient's history of lumbar surgery and the recurrence of symptoms after surgery suggest a possible mechanical cause, but the spread of symptoms to involve the arms makes this less likely. The patient's history of fibromyalgia and depression could suggest a functional neurological disorder, but the objective findings of weakness and sensory loss make this less likely. The patient's history of gastric bypass surgery raises the possibility of a nutritional deficiency, such as vitamin B12 deficiency, but her vitamin B12 levels are normal. The patient's symptoms initially improved with IVIG, which is consistent with CIDP, but her symptoms have since progressed despite treatment. The patient's MRI shows no evidence of cord compression, nerve-root impingement, or a demyelinating process, which makes multiple sclerosis less likely. The patient's nerve conduction studies and electromyography show evidence of a peripheral neuropathy, which is consistent with CIDP. However, the patient's somatosensory evoked potentials suggest a disruption of central conduction, which is not typical of CIDP. Given the patient's history, physical examination, and test results, the most likely diagnosis is CIDP that is not responding to treatment.\n\nDiagnosis: Refractory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)""
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10.1056/NEJMcpc1707557,"Case 34-2017 — A 76-Year-Old Man with Fever, Weight Loss, and Weakness",,West Nile virus encephalitis.,"Arboviral encephalitis and acute flaccid paralysis, most likely due to West Nile virus.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:            A 76-year-old man was admitted to this hospital in the late summer because of weight loss, generalized weakness, and fever.

The patient had been well until 3 weeks before admission, when he began to have decreased energy and poor appetite, symptoms that were associated with a weight loss of 4.5 kg. The next week, he was evaluated by his primary care physician. The patient reported dyspnea on exertion, diffuse myalgias, and severe fatigue that prevented him from engaging in his usual activities of walking outside, gardening, and swimming in the ocean. On examination, the temperature was 36.6°C, the blood pressure 124/73 mm Hg, the pulse 59 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. The rest of the physical examination was unremarkable.

Table 1.

Laboratory Data.
Blood levels of electrolytes, glucose, 25-hydroxyvitamin D, vitamin B12, and thyrotropin were normal, as were the results of renal- and liver-function tests and the erythrocyte sedimentation rate. Tests for hepatitis C antibodies, antitreponemal antibodies, human immunodeficiency virus (HIV) p24 antigen, and HIV type 1 and type 2 antibodies were negative; other laboratory test results are shown in Table 1. A stool test was positive for occult blood, and a diagnostic colonoscopy was scheduled.

Three days before admission, the patient felt feverish but did not check his temperature at home. Fevers continued, despite the use of acetaminophen. One day before admission, he had one episode of nonbloody, nonbilious vomiting. On the day of admission, the patient had an unwitnessed fall while he was standing in the bathroom; he reported that he had felt generally weak and had tried to sit down but fell backward and struck his head, without loss of consciousness. He was found on the floor by a family member and was unable to stand up. He was brought to the emergency department of this hospital.

On evaluation in the emergency department, the patient reported generalized myalgias but no headache, photophobia, or neck stiffness. He had a history of hypertension, non–insulin-dependent diabetes mellitus, and vitamin D deficiency. Medications included lisinopril and aspirin; the diabetes was controlled by diet. He had no family history of cancer or autoimmune disease. He had not smoked tobacco in 30 years but had previously smoked 1 pack of cigarettes per day for 20 years. He drank alcohol occasionally and did not use illicit drugs. He was retired, resided in New England, and had not traveled outside the region in several years. He did not have pets or known exposures to bats. He had recently cleaned out the basement of his home, where he had occasionally seen mice.

On examination, the temperature was 38.9°C, the blood pressure 140/64 mm Hg, the pulse 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. He was diaphoretic but did not appear ill. He was alert and oriented, and he answered questions appropriately. Examination of cranial nerves II through XII was normal. Strength and sensation to light touch were intact in the arms and legs. Deep-tendon reflexes in the arms and legs were normal; the plantar reflex was flexor bilaterally. Examination of the neck, heart, lungs, and abdomen was normal. There was no rash. Blood specimens were obtained for culture. A urinalysis was unremarkable; other laboratory test results are shown in Table 1. Imaging studies were obtained.

Dr. Pamela W. Schaefer: Computed tomography of the head, chest, abdomen, and pelvis was performed without the administration of intravenous contrast material. Imaging studies of the head did not show evidence of intracranial hemorrhage or territorial infarction. The lungs were normal, with no pleural effusion or lymphadenopathy. Mild circumferential thickening of the middle and distal esophagus was noted. No focal hepatic lesions, thickening or distention of the gastrointestinal tract, or suspicious lytic or blastic lesions of the bones were noted.

Dr. Robbins: The patient was admitted to the hospital. During the next 12 hours, altered mental status developed, with progressive confusion, difficulties with word finding, and inability to consistently follow commands. Several attempts at lumbar puncture for analysis of the cerebrospinal fluid (CSF) were unsuccessful, and empirical treatment with intravenous vancomycin, ceftriaxone, ampicillin, and acyclovir was initiated. Additional studies were obtained.

Dr. Schaefer: Magnetic resonance imaging (MRI) of the head was performed with and without the administration of intravenous contrast material. Fluid-attenuated inversion recovery (FLAIR) images showed scattered foci of signal abnormalities in the supratentorial white matter, with no evidence of intracranial mass, hemorrhage, or acute infarction.

Dr. Robbins: Electroencephalography revealed intermittent irregular delta slowing that was most prominent in the left frontocentral area and intermittent diffuse theta slowing in the background, with no epileptiform abnormalities.

On the second hospital day, a lumbar puncture revealed an opening pressure of 19.5 cm of water; other results are shown in Table 1. Doxycycline was administered orally. Fevers continued, despite the administration of acetaminophen. The blood cultures had no growth. Progressive tachypnea developed, and the patient was unable to lie in a recumbent position to undergo repeat MRI of the head. Elective intubation was performed, and mechanical ventilation was initiated.

Figure 1.

MRI of the Head.
Dr. Schaefer: On the fourth hospital day, repeat MRI of the head was performed. FLAIR images showed new mild, diffuse hyperintensity in the sulci, and FLAIR and T2-weighted images showed mild hyperintensity in the medial thalami and medial temporal lobes (Figure 1).

Dr. Robbins: Physical examination, which was performed while the patient was not receiving sedation, revealed decreased tone and no spontaneous movements of the arms or legs, findings consistent with flaccid paralysis. There was also no withdrawal in response to nail-bed pressure, and deep-tendon reflexes were absent in the arms, knees, and ankles bilaterally. The patient opened his eyes but did not regard or track the examiner and did not respond to requests. The diameter of the pupils was 3 mm bilaterally and decreased to 2 mm in response to bright light. The corneal reflexes and cough reflex were intact, but there was no grimace in response to pressure in the supraorbital notch.

On the 10th hospital day, nerve-conduction studies were performed. The sensory responses of the left median and ulnar nerves were prolonged and had moderately-to-severely reduced amplitude, and the motor responses of the bilateral median nerves had severely reduced amplitude, normal conduction velocities, and normal durations. Stimulation of the muscles by means of needle electromyography revealed abundant fibrillation potentials and positive sharp waves in the left deltoid, extensor digitorum communis, first dorsal interosseous, and tibialis anterior muscles, as well as increased insertional activity in the left vastus lateralis and medial gastrocnemius muscles and no voluntary motor units in the left arm or leg.

A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 76-year-old man was admitted to this hospital in the late summer because of weight loss, generalized weakness, and fever.

The patient had been well until 3 weeks before admission, when he began to have decreased energy and poor appetite, symptoms that were associated with a weight loss of 4.5 kg. The next week, he was evaluated by his primary care physician. The patient reported dyspnea on exertion, diffuse myalgias, and severe fatigue that prevented him from engaging in his usual activities of walking outside, gardening, and swimming in the ocean. On examination, the temperature was 36.6°C, the blood pressure 124/73 mm Hg, the pulse 59 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. The rest of the physical examination was unremarkable.

Table 1.

Laboratory Data.
Blood levels of electrolytes, glucose, 25-hydroxyvitamin D, vitamin B12, and thyrotropin were normal, as were the results of renal- and liver-function tests and the erythrocyte sedimentation rate. Tests for hepatitis C antibodies, antitreponemal antibodies, human immunodeficiency virus (HIV) p24 antigen, and HIV type 1 and type 2 antibodies were negative; other laboratory test results are shown in Table 1. A stool test was positive for occult blood, and a diagnostic colonoscopy was scheduled.

Three days before admission, the patient felt feverish but did not check his temperature at home. Fevers continued, despite the use of acetaminophen. One day before admission, he had one episode of nonbloody, nonbilious vomiting. On the day of admission, the patient had an unwitnessed fall while he was standing in the bathroom; he reported that he had felt generally weak and had tried to sit down but fell backward and struck his head, without loss of consciousness. He was found on the floor by a family member and was unable to stand up. He was brought to the emergency department of this hospital.

On evaluation in the emergency department, the patient reported generalized myalgias but no headache, photophobia, or neck stiffness. He had a history of hypertension, non–insulin-dependent diabetes mellitus, and vitamin D deficiency. Medications included lisinopril and aspirin; the diabetes was controlled by diet. He had no family history of cancer or autoimmune disease. He had not smoked tobacco in 30 years but had previously smoked 1 pack of cigarettes per day for 20 years. He drank alcohol occasionally and did not use illicit drugs. He was retired, resided in New England, and had not traveled outside the region in several years. He did not have pets or known exposures to bats. He had recently cleaned out the basement of his home, where he had occasionally seen mice.

On examination, the temperature was 38.9°C, the blood pressure 140/64 mm Hg, the pulse 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. He was diaphoretic but did not appear ill. He was alert and oriented, and he answered questions appropriately. Examination of cranial nerves II through XII was normal. Strength and sensation to light touch were intact in the arms and legs. Deep-tendon reflexes in the arms and legs were normal; the plantar reflex was flexor bilaterally. Examination of the neck, heart, lungs, and abdomen was normal. There was no rash. Blood specimens were obtained for culture. A urinalysis was unremarkable; other laboratory test results are shown in Table 1. Imaging studies were obtained.

Dr. Pamela W. Schaefer: Computed tomography of the head, chest, abdomen, and pelvis was performed without the administration of intravenous contrast material. Imaging studies of the head did not show evidence of intracranial hemorrhage or territorial infarction. The lungs were normal, with no pleural effusion or lymphadenopathy. Mild circumferential thickening of the middle and distal esophagus was noted. No focal hepatic lesions, thickening or distention of the gastrointestinal tract, or suspicious lytic or blastic lesions of the bones were noted.

Dr. Robbins: The patient was admitted to the hospital. During the next 12 hours, altered mental status developed, with progressive confusion, difficulties with word finding, and inability to consistently follow commands. Several attempts at lumbar puncture for analysis of the cerebrospinal fluid (CSF) were unsuccessful, and empirical treatment with intravenous vancomycin, ceftriaxone, ampicillin, and acyclovir was initiated. Additional studies were obtained.

Dr. Schaefer: Magnetic resonance imaging (MRI) of the head was performed with and without the administration of intravenous contrast material. Fluid-attenuated inversion recovery (FLAIR) images showed scattered foci of signal abnormalities in the supratentorial white matter, with no evidence of intracranial mass, hemorrhage, or acute infarction.

Dr. Robbins: Electroencephalography revealed intermittent irregular delta slowing that was most prominent in the left frontocentral area and intermittent diffuse theta slowing in the background, with no epileptiform abnormalities.

On the second hospital day, a lumbar puncture revealed an opening pressure of 19.5 cm of water; other results are shown in Table 1. Doxycycline was administered orally. Fevers continued, despite the administration of acetaminophen. The blood cultures had no growth. Progressive tachypnea developed, and the patient was unable to lie in a recumbent position to undergo repeat MRI of the head. Elective intubation was performed, and mechanical ventilation was initiated.

Figure 1.

MRI of the Head.
Dr. Schaefer: On the fourth hospital day, repeat MRI of the head was performed. FLAIR images showed new mild, diffuse hyperintensity in the sulci, and FLAIR and T2-weighted images showed mild hyperintensity in the medial thalami and medial temporal lobes (Figure 1).

Dr. Robbins: Physical examination, which was performed while the patient was not receiving sedation, revealed decreased tone and no spontaneous movements of the arms or legs, findings consistent with flaccid paralysis. There was also no withdrawal in response to nail-bed pressure, and deep-tendon reflexes were absent in the arms, knees, and ankles bilaterally. The patient opened his eyes but did not regard or track the examiner and did not respond to requests. The diameter of the pupils was 3 mm bilaterally and decreased to 2 mm in response to bright light. The corneal reflexes and cough reflex were intact, but there was no grimace in response to pressure in the supraorbital notch.

On the 10th hospital day, nerve-conduction studies were performed. The sensory responses of the left median and ulnar nerves were prolonged and had moderately-to-severely reduced amplitude, and the motor responses of the bilateral median nerves had severely reduced amplitude, normal conduction velocities, and normal durations. Stimulation of the muscles by means of needle electromyography revealed abundant fibrillation potentials and positive sharp waves in the left deltoid, extensor digitorum communis, first dorsal interosseous, and tibialis anterior muscles, as well as increased insertional activity in the left vastus lateralis and medial gastrocnemius muscles and no voluntary motor units in the left arm or leg.

A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Eastern Equine Encephalitis (EEE)\n\nThe patient's symptoms of fever, weight loss, generalized weakness, and altered mental status, along with the MRI findings of hyperintensity in the medial thalami and medial temporal lobes, suggest a central nervous system infection. The patient's residence in New England and the timing of his illness in late summer are consistent with arbovirus infection, specifically Eastern Equine Encephalitis (EEE), which is transmitted by mosquitoes. The patient's recent activity of cleaning out a basement where he had seen mice could have increased his exposure to mosquitoes. The nerve conduction studies showing severely reduced amplitude and the electromyography revealing abundant fibrillation potentials and positive sharp waves in multiple muscles are consistent with a severe neurologic disease, such as EEE. The absence of voluntary motor units in the left arm or leg suggests a severe, potentially irreversible, neurologic damage. The patient's lack of response to broad-spectrum antibiotics and antiviral medications further supports the diagnosis of a viral infection not covered by these treatments, such as EEE.""
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        ""content"": ""The patient is a 76-year-old man presenting with weight loss, generalized weakness, fever, and altered mental status. The differential diagnosis for this patient includes malignancy, autoimmune disease, infectious disease, and neurodegenerative disease. The patient's age and weight loss could suggest malignancy, but imaging studies did not reveal any suspicious lesions. The patient's symptoms of fever and altered mental status could suggest an infectious disease. The patient's history of cleaning out a basement where he had seen mice suggests possible exposure to hantavirus or other rodent-borne diseases. However, the patient's neurological symptoms, including confusion, difficulties with word finding, and inability to consistently follow commands, as well as the findings on MRI and nerve-conduction studies, suggest a neurological disease. The MRI findings of scattered foci of signal abnormalities in the supratentorial white matter and mild hyperintensity in the medial thalami and medial temporal lobes could suggest a neurodegenerative disease such as Alzheimer's disease or a prion disease such as Creutzfeldt-Jakob disease. However, the rapid progression of symptoms and the findings on nerve-conduction studies of severely reduced amplitude of the motor responses of the bilateral median nerves and no voluntary motor units in the left arm or leg suggest a more acute neurological disease such as Guillain-Barr\u00e9 syndrome or a variant thereof. The patient's history of recent exposure to mice could suggest a variant of Guillain-Barr\u00e9 syndrome known as Miller Fisher syndrome, which can be triggered by infection with Campylobacter jejuni, a bacterium that can be carried by rodents. However, the patient's symptoms of fever and altered mental status, as well as the findings on lumbar puncture, suggest a central nervous system infection rather than a peripheral nervous system disease such as Guillain-Barr\u00e9 syndrome. The patient's history of recent exposure to mice and the findings on lumbar puncture of lymphocytic pleocytosis and elevated protein level suggest a diagnosis of lymphocytic choriomeningitis, a viral infection that can be transmitted by rodents.\n\nDiagnosis: Lymphocytic choriomeningitis.""
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}",Lymphocytic choriomeningitis,N
0.1056/NEJMcpc1703513,"Case 32-2017 — A 64-Year-Old Man with Dyspnea, Wheezing, Headache, Cough, and Night Sweats",,Eosinophilic granulomatosis with polyangiitis.,Eosinophilic granulomatosis with polyangiitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:         A 64-year-old man was evaluated in the emergency department of this hospital because of dyspnea, wheezing, headaches, cough, and night sweats.

Approximately 6 years before this presentation, the patient had received a diagnosis of fibromyalgia, which had been made by a rheumatologist at another hospital. Two years before this presentation, the patient had had a sudden onset of pain on the right side of the lower back and buttock, with hypoesthesia and weakness in the right leg. Magnetic resonance imaging (MRI) revealed lumbosacral disk protrusion at L5–S1, with moderate-to-severe foraminal encroachment on the right side. Needle electromyography revealed evidence of L5 radiculopathy on the right side. Neurosurgery consultants recommended physical therapy, and two glucocorticoid injections were administered, which improved symptoms. However, 2 months later, electromyography revealed persistent active L5 radiculopathy on the right side that had not improved since the previous study had been obtained.

Approximately 1.5 years before this presentation, the patient’s rheumatologist reported that the patient had a persistent right foot drop and persistent tenderness of the paraspinal muscles. In addition, a diagnosis of carpal tunnel syndrome was made on the basis of the gradual onset of bilateral hand and wrist discomfort and hand paresthesias.

Table 1.

Laboratory Data.
Approximately 5 months before this presentation, the patient noted the onset of a cough that produced thin yellow sputum. During the next month, exertional dyspnea, chest tightness, and wheezing developed. Six weeks later (9 weeks before this presentation), the patient was evaluated by his primary care physician at another hospital. On examination, rhonchi and wheezing were noted; the remainder of the examination was reportedly normal. Laboratory test results are shown in Table 1. A chest radiograph was reportedly normal. A diagnosis of bronchitis was made, and an albuterol inhaler and azithromycin were prescribed. The patient was referred to an allergist, because there were concerns about allergic bronchitis.

On evaluation by the allergist, epicutaneous and intradermal skin tests revealed no reaction to pollens, molds (including aspergillus), or dust mites. Pulmonary-function testing revealed a forced expiratory volume in 1 second (FEV1) of 2.51 liters (77% of the predicted value), a forced vital capacity (FVC) of 3.03 liters (70% of the predicted value), and a ratio of FEV1 to FVC of 83%; these results were interpreted to be indicative of a restrictive ventilatory defect. There was no improvement after the administration of a bronchodilator; a methacholine challenge was not performed. The fraction of exhaled nitric oxide (Feno) was 112 ppb (reference range, <25). Budesonide–formoterol was prescribed. Two weeks later, the wheezing and cough had resolved. Repeat pulmonary-function testing revealed improvements, including an FEV1 of 3.05 liters (94% of the predicted value), an FVC of 3.55 liters (82% of the predicted value), and a ratio of FEV1 to FVC of 86%. The Feno had decreased to 59 ppb.

Ten days before this presentation, lethargy, myalgias, chills, headaches, anorexia, and night sweats developed. Nine days later, the patient was evaluated by his primary care physician because of recurrent cough, night sweats, myalgia, and fatigue. The temperature was 37.8°C, the heart rate 105 beats per minute, the blood pressure 100/70 mm Hg, and the oxygen saturation 98% while the patient was breathing ambient air. The breath sounds were described as harsh. A urinalysis was notable for the presence of microscopic hematuria; other laboratory test results are shown in Table 1. Doxycycline was prescribed empirically for possible Lyme disease.

The next day, the patient presented to the emergency department of this hospital for further evaluation. He reported bitemporal headaches, and he described the pain as bandlike; the headaches had occurred intermittently at first and then constantly during the previous 3 days. He also reported associated neck stiffness and photophobia. He had a fever, aching of the jaw muscles with chewing, and diffuse aches, including joint pain of the hands, fingers, spine, hips, and knees. Nausea with one episode of emesis had occurred after he had taken a dose of doxycycline on an empty stomach; he took a total of three doses and then discontinued the medication when the serologic test for Lyme disease was reported as negative. He had no weight loss, vision changes, or other cardiac, pulmonary, joint, ocular, or neurologic symptoms.

The patient had undergone surgery for knee osteoarthritis, had received physical therapy and glucocorticoid injections for rotator-cuff tendinopathies, and had had an appendectomy at 19 years of age. He had neck osteoarthritis, cervical spondylosis, sleep apnea, and peptic ulcer disease. He had had a negative tuberculin skin test in the past. Medications included a budesonide–formoterol inhaler. Allergies reportedly included aspirin, which was noted to cause tightness in the throat.

The patient lived with his wife and worked in a health care facility, where he was exposed to patients and multiple sick contacts. He drank alcohol on social occasions; he had smoked two packs of cigarettes per week during college and smoked cigars intermittently thereafter. He had traveled to Florida 1 month before this evaluation and to Europe and the Caribbean during the previous 8 months; he had had no animal or insect exposures. His father had died at 54 years of age from complications of type 2 diabetes mellitus; his mother had had hypothyroidism and had died at 83 years of age from acute leukemia. A sister had systemic lupus erythematosus, scleroderma, and Hashimoto’s thyroiditis.

On examination, the temperature was 38.7°C, the heart rate 118 beats per minute, the blood pressure 133/74 mm Hg, and the oxygen saturation 96% while the patient was breathing ambient air. He appeared mildly ill. The pupils were equal, round, and reactive to light. There was no tenderness on the scalp or head. The neck was described as stiff. Inspiratory crackles were present in both lungs. There was mild synovial thickening in the hands, a finding consistent with chronic arthritic changes. There was no asymmetry on neurologic strength testing. The remainder of the examination was normal.

Results of coagulation tests were normal, and the IgE level was less than 5 IU per milliliter (reference range, 0 to 100). Other laboratory test results are shown in Table 1.

Dr. Florian J. Fintelmann: Portable chest radiography showed clear, well-inflated lungs. Computed tomography (CT) of the head, performed without the administration of contrast material, showed signs of chronic sinusitis, including opacification and wall thickening in the frontal, ethmoid, and maxillary sinuses.

Dr. Nagarur: Because of the persistent headache and neck stiffness, a lumbar puncture was performed and cerebrospinal fluid (CSF) was obtained. Analysis of the CSF revealed a nucleated-cell count of 1 per cubic millimeter and a protein level of 30 mg per deciliter (reference range, 5 to 55). (The glucose level was not checked, and the opening pressure was not recorded.) A Gram’s stain of the CSF showed no polymorphonuclear cells or organisms. The patient was admitted to the hospital. Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:       A 64-year-old man was evaluated in the emergency department of this hospital because of dyspnea, wheezing, headaches, cough, and night sweats.

Approximately 6 years before this presentation, the patient had received a diagnosis of fibromyalgia, which had been made by a rheumatologist at another hospital. Two years before this presentation, the patient had had a sudden onset of pain on the right side of the lower back and buttock, with hypoesthesia and weakness in the right leg. Magnetic resonance imaging (MRI) revealed lumbosacral disk protrusion at L5–S1, with moderate-to-severe foraminal encroachment on the right side. Needle electromyography revealed evidence of L5 radiculopathy on the right side. Neurosurgery consultants recommended physical therapy, and two glucocorticoid injections were administered, which improved symptoms. However, 2 months later, electromyography revealed persistent active L5 radiculopathy on the right side that had not improved since the previous study had been obtained.

Approximately 1.5 years before this presentation, the patient’s rheumatologist reported that the patient had a persistent right foot drop and persistent tenderness of the paraspinal muscles. In addition, a diagnosis of carpal tunnel syndrome was made on the basis of the gradual onset of bilateral hand and wrist discomfort and hand paresthesias.

Table 1.

Laboratory Data.
Approximately 5 months before this presentation, the patient noted the onset of a cough that produced thin yellow sputum. During the next month, exertional dyspnea, chest tightness, and wheezing developed. Six weeks later (9 weeks before this presentation), the patient was evaluated by his primary care physician at another hospital. On examination, rhonchi and wheezing were noted; the remainder of the examination was reportedly normal. Laboratory test results are shown in Table 1. A chest radiograph was reportedly normal. A diagnosis of bronchitis was made, and an albuterol inhaler and azithromycin were prescribed. The patient was referred to an allergist, because there were concerns about allergic bronchitis.

On evaluation by the allergist, epicutaneous and intradermal skin tests revealed no reaction to pollens, molds (including aspergillus), or dust mites. Pulmonary-function testing revealed a forced expiratory volume in 1 second (FEV1) of 2.51 liters (77% of the predicted value), a forced vital capacity (FVC) of 3.03 liters (70% of the predicted value), and a ratio of FEV1 to FVC of 83%; these results were interpreted to be indicative of a restrictive ventilatory defect. There was no improvement after the administration of a bronchodilator; a methacholine challenge was not performed. The fraction of exhaled nitric oxide (Feno) was 112 ppb (reference range, <25). Budesonide–formoterol was prescribed. Two weeks later, the wheezing and cough had resolved. Repeat pulmonary-function testing revealed improvements, including an FEV1 of 3.05 liters (94% of the predicted value), an FVC of 3.55 liters (82% of the predicted value), and a ratio of FEV1 to FVC of 86%. The Feno had decreased to 59 ppb.

Ten days before this presentation, lethargy, myalgias, chills, headaches, anorexia, and night sweats developed. Nine days later, the patient was evaluated by his primary care physician because of recurrent cough, night sweats, myalgia, and fatigue. The temperature was 37.8°C, the heart rate 105 beats per minute, the blood pressure 100/70 mm Hg, and the oxygen saturation 98% while the patient was breathing ambient air. The breath sounds were described as harsh. A urinalysis was notable for the presence of microscopic hematuria; other laboratory test results are shown in Table 1. Doxycycline was prescribed empirically for possible Lyme disease.

The next day, the patient presented to the emergency department of this hospital for further evaluation. He reported bitemporal headaches, and he described the pain as bandlike; the headaches had occurred intermittently at first and then constantly during the previous 3 days. He also reported associated neck stiffness and photophobia. He had a fever, aching of the jaw muscles with chewing, and diffuse aches, including joint pain of the hands, fingers, spine, hips, and knees. Nausea with one episode of emesis had occurred after he had taken a dose of doxycycline on an empty stomach; he took a total of three doses and then discontinued the medication when the serologic test for Lyme disease was reported as negative. He had no weight loss, vision changes, or other cardiac, pulmonary, joint, ocular, or neurologic symptoms.

The patient had undergone surgery for knee osteoarthritis, had received physical therapy and glucocorticoid injections for rotator-cuff tendinopathies, and had had an appendectomy at 19 years of age. He had neck osteoarthritis, cervical spondylosis, sleep apnea, and peptic ulcer disease. He had had a negative tuberculin skin test in the past. Medications included a budesonide–formoterol inhaler. Allergies reportedly included aspirin, which was noted to cause tightness in the throat.

The patient lived with his wife and worked in a health care facility, where he was exposed to patients and multiple sick contacts. He drank alcohol on social occasions; he had smoked two packs of cigarettes per week during college and smoked cigars intermittently thereafter. He had traveled to Florida 1 month before this evaluation and to Europe and the Caribbean during the previous 8 months; he had had no animal or insect exposures. His father had died at 54 years of age from complications of type 2 diabetes mellitus; his mother had had hypothyroidism and had died at 83 years of age from acute leukemia. A sister had systemic lupus erythematosus, scleroderma, and Hashimoto’s thyroiditis.

On examination, the temperature was 38.7°C, the heart rate 118 beats per minute, the blood pressure 133/74 mm Hg, and the oxygen saturation 96% while the patient was breathing ambient air. He appeared mildly ill. The pupils were equal, round, and reactive to light. There was no tenderness on the scalp or head. The neck was described as stiff. Inspiratory crackles were present in both lungs. There was mild synovial thickening in the hands, a finding consistent with chronic arthritic changes. There was no asymmetry on neurologic strength testing. The remainder of the examination was normal.

Results of coagulation tests were normal, and the IgE level was less than 5 IU per milliliter (reference range, 0 to 100). Other laboratory test results are shown in Table 1.

Dr. Florian J. Fintelmann: Portable chest radiography showed clear, well-inflated lungs. Computed tomography (CT) of the head, performed without the administration of contrast material, showed signs of chronic sinusitis, including opacification and wall thickening in the frontal, ethmoid, and maxillary sinuses.

Dr. Nagarur: Because of the persistent headache and neck stiffness, a lumbar puncture was performed and cerebrospinal fluid (CSF) was obtained. Analysis of the CSF revealed a nucleated-cell count of 1 per cubic millimeter and a protein level of 30 mg per deciliter (reference range, 5 to 55). (The glucose level was not checked, and the opening pressure was not recorded.) A Gram’s stain of the CSF showed no polymorphonuclear cells or organisms. The patient was admitted to the hospital. Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of cough, dyspnea, chest tightness, and wheezing, along with the high fraction of exhaled nitric oxide (FeNO) and the restrictive pattern on pulmonary function tests, suggest a pulmonary disorder. The patient's symptoms improved with budesonide-formoterol, which is used to treat asthma and COPD, but the patient's symptoms are not completely consistent with either of these conditions. The patient also has a history of fibromyalgia and carpal tunnel syndrome, which are not typically associated with pulmonary disorders. The patient's recent symptoms of fever, myalgias, chills, headaches, anorexia, and night sweats, along with the presence of microscopic hematuria, suggest a systemic inflammatory or infectious process. The patient's negative serologic test for Lyme disease and the lack of improvement with doxycycline make Lyme disease unlikely. The patient's exposure to patients and multiple sick contacts at his job in a healthcare facility raises the possibility of a communicable disease, but the patient's symptoms are not specific to any particular infectious disease. The patient's family history of autoimmune diseases, including systemic lupus erythematosus and scleroderma, raises the possibility of an autoimmune or connective tissue disease. The patient's symptoms and test results do not clearly point to a specific diagnosis, but the combination of pulmonary, systemic, and neurologic symptoms, along with the patient's personal and family medical history, suggest a systemic autoimmune or connective tissue disease.\n\nDiagnosis: Systemic autoimmune or connective tissue disease.""
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        ""content"": ""This is a 64-year-old man with a history of fibromyalgia, lumbosacral disk protrusion, and carpal tunnel syndrome who presents with dyspnea, wheezing, headaches, cough, and night sweats. He also has a history of chronic sinusitis. His symptoms have been ongoing for several months and have not improved with treatment for bronchitis. His symptoms and history suggest a possible autoimmune or inflammatory condition. The differential diagnosis includes conditions such as rheumatoid arthritis, systemic lupus erythematosus, vasculitis, and sarcoidosis. His negative Lyme disease test and lack of gastrointestinal symptoms make Lyme disease and inflammatory bowel disease less likely. His pulmonary function tests and symptoms of cough and wheezing suggest a restrictive lung disease, which could be caused by conditions such as sarcoidosis or fibrotic lung disease. His history of fibromyalgia and carpal tunnel syndrome, along with his new symptoms, could suggest a systemic autoimmune condition such as rheumatoid arthritis or lupus, but he does not have the typical rash or renal involvement seen in lupus. His headaches and neck stiffness could suggest a central nervous system involvement, which could be seen in conditions such as vasculitis or sarcoidosis. His elevated ESR and CRP suggest an ongoing inflammatory process. Given his symptoms and test results, sarcoidosis is a likely diagnosis. \n\nDiagnosis: Sarcoidosis.""
      },
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  ""usage"": {
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}",Sarcoidosis,N
10.1056/NEJMcpc1706106,"Case 31-2017 — A 19-Month-Old Girl with Failure to Thrive
List of authors.",,The diencephalic syndrome due to a pilomyxoid astrocytoma.,The diencephalic syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 19-month-old girl was admitted to this hospital because of failure to thrive.

The patient had been born in Puerto Rico by induced vaginal delivery after 41 weeks of gestation. Her mother did not smoke, drink alcohol, or take any medications during the pregnancy. Results of prenatal laboratory testing had reportedly suggested maternal hyperthyroidism, but follow-up studies revealed normal thyroid function. The delivery was uncomplicated, and the birth weight was 3.2 kg (50th percentile).

Figure 1.

Growth Charts.
The patient’s growth had been assessed as normal until she was 9 months of age, when she attended a clinic visit. The weight was 7.0 kg (10th percentile), which was lower than the weight at the most recent clinic visit, 2 months earlier (7.1 kg [27th percentile]) (Figure 1). Follow-up appointments were scheduled.

Table 1.

Laboratory Data.
The patient returned to the clinic when she was 12 months of age, and the weight was 7.3 kg (6th percentile). The hemoglobin level, hematocrit, red-cell count, and red-cell indexes were normal, as were blood levels of total protein, albumin, globulin, alkaline phosphatase, total bilirubin, total carnitine, free carnitine, and ammonia; other laboratory test results are shown in Table 1. Urinalysis revealed clear, yellow urine, with a specific gravity of 1.025, a pH of 6.0, 2+ leukocyte esterase, and trace blood by dipstick; on microscopic examination, squamous epithelial cells and bacteria were present and there were 2 to 5 white cells and 0 to 2 red cells per high-power field. A urine culture grew very few mixed bacteria. Nutritional shakes were prescribed through the Special Supplemental Nutrition Program for Women, Infants, and Children.

When the patient attended a clinic visit 6 weeks later, the weight was 7.7 kg (7th percentile). The hemoglobin level, hematocrit, red-cell count, and red-cell indexes were normal; other laboratory test results are shown in Table 1. The patient was referred for evaluation by a geneticist, who reportedly did not suspect a genetic cause of poor weight gain. When the patient was 14.5 months of age, she was seen by a nutritionist; a detailed meal plan that was designed to provide a balanced, high-kilocalorie diet was recommended. The results of a sweat chloride test were reportedly normal.

One month later, the patient was evaluated by an endocrinologist. Blood levels of total protein, albumin, globulin, alkaline phosphatase, total bilirubin, direct bilirubin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, total carnitine, free carnitine, follicle-stimulating hormone, and estradiol were normal; other laboratory test results are shown in Table 1. A radiographic assessment of bone age in the left hand (according to the method of Greulich and Pyle) revealed a bone age of 1 year 6 months, which was within 1 SD of normal. Methimazole was prescribed; the patient’s mother administered the drug for 3 days before stopping because of unspecified side effects.

Two weeks later, the patient was seen by a second endocrinologist. The patient’s mother reported that the child was an active toddler and that she had a strong appetite and ate a wide variety of foods throughout the day; however, she had not gained weight despite following the meal plan recommended by the nutritionist. On examination, the patient was thin, with wasting of the buttocks. There was no hepatosplenomegaly, and the external female genitalia were classified as Tanner stage 1 (with stages ranging from 1 to 5 and higher stages indicating more advanced pubertal development). A glucometer and test strips were provided to the mother, with instructions to record the fasting and 2-hour postprandial blood glucose levels. Ten days after this clinic visit, tests for thyrotropin-receptor antibodies and thyroid-stimulating immunoglobulins were negative. The hemoglobin level, hematocrit, red-cell count, and red-cell indexes were normal, as were blood levels of total protein, albumin, globulin, alkaline phosphatase, total bilirubin, and glycated hemoglobin; other test results are shown in Table 1. Results of ultrasonography of the thyroid gland, which was performed 3 days later, were normal.

At a follow-up visit in the endocrinology clinic when the patient was 17 months of age, the weight was 7.6 kg (<2nd percentile). Tests for antithyroglobulin antibodies, anti–tissue transglutaminase IgA and IgG antibodies, and antigliadin IgA and IgG antibodies were negative, and blood levels of phosphorus, total protein, albumin, globulin, alkaline phosphatase, total bilirubin, thyroid peroxidase, and 25-hydroxyvitamin D were normal; other laboratory test results are shown in Table 1. The endocrinologist recommended that the patient be evaluated in a multidisciplinary, coordinated pediatric-care system in the continental United States, and the patient and her mother relocated to New England the following month.

When the patient was 19 months of age, she was seen in a pediatric clinic and directly admitted to the inpatient pediatric unit of a community hospital affiliated with this hospital for evaluation of failure to thrive. On admission, the patient’s mother reported that the child ate large amounts of food (equal to the amounts eaten by her 5-year-old brother) and never seemed satisfied. The patient had no abdominal pain or diarrhea. When she was between 10 and 12 months of age, she had begun to vomit intermittently. Nonbloody, nonbilious emesis occurred approximately once per week thereafter; the mother attributed the vomiting to overeating. The patient had briefly been hospitalized during infancy for influenza and at 16 months of age for bronchiolitis. She had crawled at 7 months of age, cruised at 10 months of age, and walked at 12 months of age. She walked up steps with assistance, ran, spoke eight words, pointed to indicate wants, and scribbled spontaneously. The mother described the child as happy and playful and reported that she behaved as though she were healthy. The timing of dental eruption had been normal. The patient received no medications, had no known allergies, and had received routine childhood vaccinations. Since she had moved from Puerto Rico 1 month earlier, she had been living with her mother, 5-year-old brother, and step-grandmother in an urban area of New England. The patient’s mother was healthy, her brother had attention deficit–hyperactivity disorder, and her father’s medical history was unknown.

On examination, the patient had cachexia; she otherwise appeared well and happy, was playful and active, and walked rapidly around the hospital room. The temperature was 37.2°C, the pulse 110 beats per minute, the blood pressure 125/55 mm Hg, the respiratory rate 32 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The weight was 7.4 kg (<1st percentile). The anterior fontanelle was closed, and the remainder of the physical examination was normal.

The next day, the patient was transferred to this hospital for further evaluation. The vital signs were normal, and the weight was 7.3 kg (<1st percentile); the results of the physical examination were otherwise unchanged. Tests for anti–tissue transglutaminase IgA and IgG antibodies and human immunodeficiency virus infection were negative. The hemoglobin level, hematocrit, red-cell count, red-cell indexes, and erythrocyte sedimentation rate were normal, as were blood levels of phosphorus, magnesium, total protein, albumin, globulin, alkaline phosphatase, total bilirubin, direct bilirubin, and C-reactive protein; other test results are shown in Table 1.

A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                A 19-month-old girl was admitted to this hospital because of failure to thrive.

The patient had been born in Puerto Rico by induced vaginal delivery after 41 weeks of gestation. Her mother did not smoke, drink alcohol, or take any medications during the pregnancy. Results of prenatal laboratory testing had reportedly suggested maternal hyperthyroidism, but follow-up studies revealed normal thyroid function. The delivery was uncomplicated, and the birth weight was 3.2 kg (50th percentile).

Figure 1.

Growth Charts.
The patient’s growth had been assessed as normal until she was 9 months of age, when she attended a clinic visit. The weight was 7.0 kg (10th percentile), which was lower than the weight at the most recent clinic visit, 2 months earlier (7.1 kg [27th percentile]) (Figure 1). Follow-up appointments were scheduled.

Table 1.

Laboratory Data.
The patient returned to the clinic when she was 12 months of age, and the weight was 7.3 kg (6th percentile). The hemoglobin level, hematocrit, red-cell count, and red-cell indexes were normal, as were blood levels of total protein, albumin, globulin, alkaline phosphatase, total bilirubin, total carnitine, free carnitine, and ammonia; other laboratory test results are shown in Table 1. Urinalysis revealed clear, yellow urine, with a specific gravity of 1.025, a pH of 6.0, 2+ leukocyte esterase, and trace blood by dipstick; on microscopic examination, squamous epithelial cells and bacteria were present and there were 2 to 5 white cells and 0 to 2 red cells per high-power field. A urine culture grew very few mixed bacteria. Nutritional shakes were prescribed through the Special Supplemental Nutrition Program for Women, Infants, and Children.

When the patient attended a clinic visit 6 weeks later, the weight was 7.7 kg (7th percentile). The hemoglobin level, hematocrit, red-cell count, and red-cell indexes were normal; other laboratory test results are shown in Table 1. The patient was referred for evaluation by a geneticist, who reportedly did not suspect a genetic cause of poor weight gain. When the patient was 14.5 months of age, she was seen by a nutritionist; a detailed meal plan that was designed to provide a balanced, high-kilocalorie diet was recommended. The results of a sweat chloride test were reportedly normal.

One month later, the patient was evaluated by an endocrinologist. Blood levels of total protein, albumin, globulin, alkaline phosphatase, total bilirubin, direct bilirubin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, total carnitine, free carnitine, follicle-stimulating hormone, and estradiol were normal; other laboratory test results are shown in Table 1. A radiographic assessment of bone age in the left hand (according to the method of Greulich and Pyle) revealed a bone age of 1 year 6 months, which was within 1 SD of normal. Methimazole was prescribed; the patient’s mother administered the drug for 3 days before stopping because of unspecified side effects.

Two weeks later, the patient was seen by a second endocrinologist. The patient’s mother reported that the child was an active toddler and that she had a strong appetite and ate a wide variety of foods throughout the day; however, she had not gained weight despite following the meal plan recommended by the nutritionist. On examination, the patient was thin, with wasting of the buttocks. There was no hepatosplenomegaly, and the external female genitalia were classified as Tanner stage 1 (with stages ranging from 1 to 5 and higher stages indicating more advanced pubertal development). A glucometer and test strips were provided to the mother, with instructions to record the fasting and 2-hour postprandial blood glucose levels. Ten days after this clinic visit, tests for thyrotropin-receptor antibodies and thyroid-stimulating immunoglobulins were negative. The hemoglobin level, hematocrit, red-cell count, and red-cell indexes were normal, as were blood levels of total protein, albumin, globulin, alkaline phosphatase, total bilirubin, and glycated hemoglobin; other test results are shown in Table 1. Results of ultrasonography of the thyroid gland, which was performed 3 days later, were normal.

At a follow-up visit in the endocrinology clinic when the patient was 17 months of age, the weight was 7.6 kg (<2nd percentile). Tests for antithyroglobulin antibodies, anti–tissue transglutaminase IgA and IgG antibodies, and antigliadin IgA and IgG antibodies were negative, and blood levels of phosphorus, total protein, albumin, globulin, alkaline phosphatase, total bilirubin, thyroid peroxidase, and 25-hydroxyvitamin D were normal; other laboratory test results are shown in Table 1. The endocrinologist recommended that the patient be evaluated in a multidisciplinary, coordinated pediatric-care system in the continental United States, and the patient and her mother relocated to New England the following month.

When the patient was 19 months of age, she was seen in a pediatric clinic and directly admitted to the inpatient pediatric unit of a community hospital affiliated with this hospital for evaluation of failure to thrive. On admission, the patient’s mother reported that the child ate large amounts of food (equal to the amounts eaten by her 5-year-old brother) and never seemed satisfied. The patient had no abdominal pain or diarrhea. When she was between 10 and 12 months of age, she had begun to vomit intermittently. Nonbloody, nonbilious emesis occurred approximately once per week thereafter; the mother attributed the vomiting to overeating. The patient had briefly been hospitalized during infancy for influenza and at 16 months of age for bronchiolitis. She had crawled at 7 months of age, cruised at 10 months of age, and walked at 12 months of age. She walked up steps with assistance, ran, spoke eight words, pointed to indicate wants, and scribbled spontaneously. The mother described the child as happy and playful and reported that she behaved as though she were healthy. The timing of dental eruption had been normal. The patient received no medications, had no known allergies, and had received routine childhood vaccinations. Since she had moved from Puerto Rico 1 month earlier, she had been living with her mother, 5-year-old brother, and step-grandmother in an urban area of New England. The patient’s mother was healthy, her brother had attention deficit–hyperactivity disorder, and her father’s medical history was unknown.

On examination, the patient had cachexia; she otherwise appeared well and happy, was playful and active, and walked rapidly around the hospital room. The temperature was 37.2°C, the pulse 110 beats per minute, the blood pressure 125/55 mm Hg, the respiratory rate 32 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The weight was 7.4 kg (<1st percentile). The anterior fontanelle was closed, and the remainder of the physical examination was normal.

The next day, the patient was transferred to this hospital for further evaluation. The vital signs were normal, and the weight was 7.3 kg (<1st percentile); the results of the physical examination were otherwise unchanged. Tests for anti–tissue transglutaminase IgA and IgG antibodies and human immunodeficiency virus infection were negative. The hemoglobin level, hematocrit, red-cell count, red-cell indexes, and erythrocyte sedimentation rate were normal, as were blood levels of phosphorus, magnesium, total protein, albumin, globulin, alkaline phosphatase, total bilirubin, direct bilirubin, and C-reactive protein; other test results are shown in Table 1.

A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 19-month-old girl with failure to thrive. She has a history of normal growth until 9 months of age, after which her weight gain slowed significantly. Despite a strong appetite and large food intake, she has not gained weight. She has no other significant symptoms, such as diarrhea or abdominal pain, and her development is normal. The differential diagnosis for failure to thrive in a child includes malnutrition, malabsorption syndromes (such as celiac disease or cystic fibrosis), metabolic disorders, endocrine disorders (such as hyperthyroidism or diabetes), and genetic syndromes. However, the patient's normal development, lack of gastrointestinal symptoms, and strong appetite make malnutrition and malabsorption syndromes less likely. Her normal sweat chloride test result makes cystic fibrosis unlikely. Her normal thyroid function tests and negative thyrotropin-receptor antibodies and thyroid-stimulating immunoglobulins make hyperthyroidism unlikely. Her normal blood glucose levels and glycated hemoglobin make diabetes unlikely. Her normal genetic evaluation makes a genetic syndrome unlikely. The patient's large food intake, failure to gain weight, and intermittent vomiting suggest a metabolic disorder. The most likely diagnosis in this case is hyperinsulinism, which can cause excessive insulin production leading to hypoglycemia and failure to thrive. \n\nDiagnosis: Hyperinsulinism.""
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}",Hyperinsulinism,N
10.1056/NEJMcpc1706100,"Case 30-2017 — A 65-Year-Old Woman with Altered Mental Status, Bacteremia, and Acute Liver Failure",,Campylobacter bacteremia in a patient with presumed autoimmune hepatitis.,Campylobacter bacteremia and sepsis in a patient with cirrhosis due to presumed autoimmune hepatitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 65-year-old woman with autoimmune hepatitis and acute liver failure was transferred to this hospital for an evaluation for liver transplantation.

The patient had been in her usual state of health until 6 years before this admission, when she received abnormal results of liver-function tests at another hospital. She underwent a follow-up evaluation that revealed an elevated antinuclear antibody titer. Levels of ceruloplasmin, _1-antitrypsin, and antimitochondrial antibodies were normal, and tests for tissue transglutaminase antibodies and viral hepatitis were negative. A presumptive diagnosis of autoimmune hepatitis with cirrhosis was made, and treatment with glucocorticoids was recommended. However, results of liver-function tests reportedly normalized without treatment during the following year.

Approximately 7 weeks before this admission, malaise, fatigue, and jaundice developed in the patient, and she was evaluated at the other hospital. The alanine aminotransferase and aspartate aminotransferase levels were elevated at 1844 IU per liter (reference range, 0 to 40) and 1451 IU per liter (reference range, 0 to 37), respectively. She had a bilirubin level of 7.9 mg per deciliter (135.1 _mol per liter; reference range, 0 to 1.0 mg per deciliter [0 to 17.1 _mol per liter]), an antinuclear antibody titer of 1:640 (reference range, <1:160), detectable anti–smooth muscle antibodies, and an IgG level of 2584 mg per deciliter (reference range, 700 to 1600). Ultrasonography of the right upper quadrant revealed a nodular liver. Prednisone therapy was begun. The patient’s condition improved, and plans were made to transition treatment from prednisone to azathioprine. However, the patient elected to taper the course of prednisone within 4 weeks and started to take natural supplements instead of the prescribed azathioprine.

Two weeks later, approximately 7 days before this admission, the patient’s daughter noted that her mother had jaundice. Four days before this admission, the patient was found on the floor of her home and was delirious; she was admitted to the other hospital. She had a temperature of 39.5°C, an albumin level of 2.4 mg per deciliter (reference range, 3.2 to 5.2), a total bilirubin level of 15.4 mg per deciliter (263.3 _mol per liter), an alanine aminotransferase level of 1040 IU per liter, an aspartate aminotransferase level of 738 IU per liter, an ammonia level of 66 _mol per liter (reference range, 11 to 51), an international normalized ratio (INR) of 5.2 (reference range, 0.9 to 1.2), a creatinine level of 0.57 mg per deciliter (50 _mol per liter; reference range, 0.5 to 1.3 mg per deciliter [44 to 115 _mol per liter]), a lactate level of 9.9 mmol per liter (89 mg per deciliter; reference range, 0.5 to 2.2 mmol per liter [5 to 20 mg per deciliter]), and a platelet count of 111,000 per cubic millimeter (reference range, 140,000 to 440,000). Abdominal ultrasonography revealed an ill-defined echogenicity of the right lobe of the liver that had not been present 3 months earlier; there was no hydronephrosis. Oral methylprednisone, intravenous vitamin K, lactulose, and rifaximin were administered.

Figure 1.

Blood-Culture Broth at the Other Hospital.
Oliguric acute kidney injury developed, with a creatinine level as high as 3.6 mg per deciliter (318 _mol per liter). Results of an evaluation of the urine sediment were unremarkable. An albumin infusion was administered, but the patient had no improvement in creatinine level or urine output. The patient’s kidney injury was considered to be consistent with the hepatorenal syndrome. Midodrine and octreotide were administered. Fever and leukocytosis (with a white-cell count as high as 27,000 per cubic millimeter [reference range, 4200 to 10,200]) developed, and a blood sample was obtained for culture. After approximately 56 hours of incubation, microbial growth was detected in the aerobic blood-culture bottle, and a Gram’s stain of the blood-culture broth showed a corkscrew-shaped gram-negative rod (Figure 1). Empirical vancomycin and ceftriaxone were administered; ceftriaxone therapy was discontinued after one dose, and piperacillin–tazobactam therapy was initiated. The patient was then transferred to the medical service of this hospital.

On admission to this hospital, the patient reported that she had had nonbloody diarrhea during the days before the evaluation at the other hospital, without nausea, vomiting, or abdominal pain. She also reported that she had coughed up blood-tinged sputum once during the weeks before admission, but she had had no hematemesis, melena, or other bleeding. The patient had a history of heavy alcohol consumption and had undergone a tubal ligation. She had taken no prescribed medications before admission to the other hospital, but she had been taking supplements, including milk thistle and buckthorn. She did not report the use of any nonsteroidal antiinflammatory drugs. The use of codeine caused nausea and vomiting.

The patient was from a city in a neighboring state and lived alone. She worked in the health care field and had an adult daughter who was healthy. For several years, she had consumed 3 to 5 half gallons of distilled spirits per week, but she stopped drinking alcohol after she received a diagnosis of autoimmune hepatitis 6 years earlier. She had a remote history of smoking and did not report the use of any illicit drugs. She had an indoor cat but no other exposure to animals, and had not traveled recently. There was no family history of liver disease.

On examination, the temperature was 37.1°C, the heart rate 65 beats per minute, the blood pressure 126/60 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. She appeared fatigued but was oriented to person, place, and time, and she could recite the days of the week backward. The sclerae were icteric and the skin was jaundiced, with scattered spider angiomata and faint ecchymoses. Auscultation of the lungs revealed bibasilar crackles. The abdomen was soft, nontender, and slightly distended, with a possible fluid wave. The liver and spleen were not palpable. Clinically significant edema was present from the lower legs to the sacrum. A limited neurologic examination revealed no asterixis.

Table 1.

Laboratory Data.
A urinalysis was unremarkable. Tests for hepatitis A virus IgM antibodies, hepatitis B virus surface antibodies, hepatitis B virus core antibodies, hepatitis B virus surface antigen, and hepatitis C virus antibodies were negative. Other laboratory test results are shown in Table 1. Imaging studies were obtained.

Figure 2.

Imaging Studies.
Dr. Efren J. Flores: A chest radiograph showed multifocal air-space opacities and bilateral pleural effusions (Figure 2A). Computed tomography (CT) of the chest, abdomen, and pelvis, performed without the intravenous administration of contrast material, confirmed the presence of diffuse ground-glass opacities predominantly in the upper lobes, central interlobular septal thickening, and a nodular hepatic contour (Figure 2B and 2C). There were multiple prominent portal and perihepatic lymph nodes and small-volume ascites.

Dr. Coromilas: Piperacillin–tazobactam, doxycycline, and trimethoprim–sulfamethoxazole were administered, and treatment with lactulose, rifaximin, albumin, midodrine, and octreotide was continued. A Gram’s stain image was provided by the other hospital; in addition, a Gram’s stain was performed at this hospital on a blood-culture isolate obtained from the other hospital. A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:             A 65-year-old woman with autoimmune hepatitis and acute liver failure was transferred to this hospital for an evaluation for liver transplantation.

The patient had been in her usual state of health until 6 years before this admission, when she received abnormal results of liver-function tests at another hospital. She underwent a follow-up evaluation that revealed an elevated antinuclear antibody titer. Levels of ceruloplasmin, _1-antitrypsin, and antimitochondrial antibodies were normal, and tests for tissue transglutaminase antibodies and viral hepatitis were negative. A presumptive diagnosis of autoimmune hepatitis with cirrhosis was made, and treatment with glucocorticoids was recommended. However, results of liver-function tests reportedly normalized without treatment during the following year.

Approximately 7 weeks before this admission, malaise, fatigue, and jaundice developed in the patient, and she was evaluated at the other hospital. The alanine aminotransferase and aspartate aminotransferase levels were elevated at 1844 IU per liter (reference range, 0 to 40) and 1451 IU per liter (reference range, 0 to 37), respectively. She had a bilirubin level of 7.9 mg per deciliter (135.1 _mol per liter; reference range, 0 to 1.0 mg per deciliter [0 to 17.1 _mol per liter]), an antinuclear antibody titer of 1:640 (reference range, <1:160), detectable anti–smooth muscle antibodies, and an IgG level of 2584 mg per deciliter (reference range, 700 to 1600). Ultrasonography of the right upper quadrant revealed a nodular liver. Prednisone therapy was begun. The patient’s condition improved, and plans were made to transition treatment from prednisone to azathioprine. However, the patient elected to taper the course of prednisone within 4 weeks and started to take natural supplements instead of the prescribed azathioprine.

Two weeks later, approximately 7 days before this admission, the patient’s daughter noted that her mother had jaundice. Four days before this admission, the patient was found on the floor of her home and was delirious; she was admitted to the other hospital. She had a temperature of 39.5°C, an albumin level of 2.4 mg per deciliter (reference range, 3.2 to 5.2), a total bilirubin level of 15.4 mg per deciliter (263.3 _mol per liter), an alanine aminotransferase level of 1040 IU per liter, an aspartate aminotransferase level of 738 IU per liter, an ammonia level of 66 _mol per liter (reference range, 11 to 51), an international normalized ratio (INR) of 5.2 (reference range, 0.9 to 1.2), a creatinine level of 0.57 mg per deciliter (50 _mol per liter; reference range, 0.5 to 1.3 mg per deciliter [44 to 115 _mol per liter]), a lactate level of 9.9 mmol per liter (89 mg per deciliter; reference range, 0.5 to 2.2 mmol per liter [5 to 20 mg per deciliter]), and a platelet count of 111,000 per cubic millimeter (reference range, 140,000 to 440,000). Abdominal ultrasonography revealed an ill-defined echogenicity of the right lobe of the liver that had not been present 3 months earlier; there was no hydronephrosis. Oral methylprednisone, intravenous vitamin K, lactulose, and rifaximin were administered.

Figure 1.

Blood-Culture Broth at the Other Hospital.
Oliguric acute kidney injury developed, with a creatinine level as high as 3.6 mg per deciliter (318 _mol per liter). Results of an evaluation of the urine sediment were unremarkable. An albumin infusion was administered, but the patient had no improvement in creatinine level or urine output. The patient’s kidney injury was considered to be consistent with the hepatorenal syndrome. Midodrine and octreotide were administered. Fever and leukocytosis (with a white-cell count as high as 27,000 per cubic millimeter [reference range, 4200 to 10,200]) developed, and a blood sample was obtained for culture. After approximately 56 hours of incubation, microbial growth was detected in the aerobic blood-culture bottle, and a Gram’s stain of the blood-culture broth showed a corkscrew-shaped gram-negative rod (Figure 1). Empirical vancomycin and ceftriaxone were administered; ceftriaxone therapy was discontinued after one dose, and piperacillin–tazobactam therapy was initiated. The patient was then transferred to the medical service of this hospital.

On admission to this hospital, the patient reported that she had had nonbloody diarrhea during the days before the evaluation at the other hospital, without nausea, vomiting, or abdominal pain. She also reported that she had coughed up blood-tinged sputum once during the weeks before admission, but she had had no hematemesis, melena, or other bleeding. The patient had a history of heavy alcohol consumption and had undergone a tubal ligation. She had taken no prescribed medications before admission to the other hospital, but she had been taking supplements, including milk thistle and buckthorn. She did not report the use of any nonsteroidal antiinflammatory drugs. The use of codeine caused nausea and vomiting.

The patient was from a city in a neighboring state and lived alone. She worked in the health care field and had an adult daughter who was healthy. For several years, she had consumed 3 to 5 half gallons of distilled spirits per week, but she stopped drinking alcohol after she received a diagnosis of autoimmune hepatitis 6 years earlier. She had a remote history of smoking and did not report the use of any illicit drugs. She had an indoor cat but no other exposure to animals, and had not traveled recently. There was no family history of liver disease.

On examination, the temperature was 37.1°C, the heart rate 65 beats per minute, the blood pressure 126/60 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 94% while the patient was breathing ambient air. She appeared fatigued but was oriented to person, place, and time, and she could recite the days of the week backward. The sclerae were icteric and the skin was jaundiced, with scattered spider angiomata and faint ecchymoses. Auscultation of the lungs revealed bibasilar crackles. The abdomen was soft, nontender, and slightly distended, with a possible fluid wave. The liver and spleen were not palpable. Clinically significant edema was present from the lower legs to the sacrum. A limited neurologic examination revealed no asterixis.

Table 1.

Laboratory Data.
A urinalysis was unremarkable. Tests for hepatitis A virus IgM antibodies, hepatitis B virus surface antibodies, hepatitis B virus core antibodies, hepatitis B virus surface antigen, and hepatitis C virus antibodies were negative. Other laboratory test results are shown in Table 1. Imaging studies were obtained.

Figure 2.

Imaging Studies.
Dr. Efren J. Flores: A chest radiograph showed multifocal air-space opacities and bilateral pleural effusions (Figure 2A). Computed tomography (CT) of the chest, abdomen, and pelvis, performed without the intravenous administration of contrast material, confirmed the presence of diffuse ground-glass opacities predominantly in the upper lobes, central interlobular septal thickening, and a nodular hepatic contour (Figure 2B and 2C). There were multiple prominent portal and perihepatic lymph nodes and small-volume ascites.

Dr. Coromilas: Piperacillin–tazobactam, doxycycline, and trimethoprim–sulfamethoxazole were administered, and treatment with lactulose, rifaximin, albumin, midodrine, and octreotide was continued. A Gram’s stain image was provided by the other hospital; in addition, a Gram’s stain was performed at this hospital on a blood-culture isolate obtained from the other hospital. A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of autoimmune hepatitis and acute liver failure. She has been experiencing malaise, fatigue, and jaundice. Her liver function tests are abnormal and she has a high antinuclear antibody titer. She also has detectable anti-smooth muscle antibodies and an elevated IgG level. She has been non-compliant with her prescribed medication and has been taking natural supplements instead. She has developed oliguric acute kidney injury, fever, and leukocytosis. A blood culture has shown a corkscrew-shaped gram-negative rod. This is indicative of a bacterial infection, specifically leptospirosis, which is known to cause liver and kidney damage. \n\nDiagnosis: Leptospirosis.""
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}",Leptospirosis,N,"{
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        ""content"": ""The patient is a 65-year-old woman with a history of autoimmune hepatitis who presents with acute liver failure, jaundice, and delirium. She also has a history of heavy alcohol consumption. Her lab results show elevated liver enzymes, bilirubin, and INR, which are indicative of liver damage and impaired liver function. She also has an elevated ammonia level, which can cause hepatic encephalopathy, a condition that can cause changes in consciousness and behavior, as seen in this patient. The patient also has acute kidney injury, which could be due to hepatorenal syndrome, a condition that can occur in patients with severe liver disease. The patient's blood culture shows a corkscrew-shaped gram-negative rod, which is indicative of a bacterial infection. Given the patient's history of autoimmune hepatitis, heavy alcohol consumption, and the current presentation with acute liver failure and infection, the most likely diagnosis is decompensated cirrhosis due to autoimmune hepatitis and alcohol-related liver disease complicated by infection with a spirochete bacterium.\n\nDiagnosis: Decompensated cirrhosis due to autoimmune hepatitis and alcohol-related liver disease complicated by spirochete bacteremia.""
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}",Decompensated cirrhosis due to autoimmune hepatitis and alcohol-related liver disease complicated by spirochete bacteremia,N
10.1056/NEJMcpc1706108,Case 29-2017 — A 59-Year-Old Woman with Pain and Swelling in the Right Hand and Ankles,,Septic arthritis due to disseminated infection with Neisseria gonorrhoeae.,Disseminated gonococcal infection with purulent arthritis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 59-year-old woman was admitted to this hospital because of stiffness, swelling, and severe pain in her right thumb and both ankles.

The patient had been well until 9 days before admission, when stiffness, swelling, and pain developed in the metacarpophalangeal joint of the right thumb that limited her ability to perform tasks such as dressing. The stiffness was not worse in the morning than during the rest of the day, and it did not improve throughout the day. The patient presented to another hospital for evaluation. Radiographs of the hand and wrist were reportedly normal.

Six days before admission, swelling and pain in both ankles developed. The patient was evaluated by her primary care physician, and a 6-day tapering course of oral methylprednisolone was prescribed. After 4 days of methylprednisolone therapy, the joint pain had progressively worsened, and the patient had difficulty walking. She presented to this hospital for evaluation.

On evaluation in the emergency department, the patient reported progressive pain in the right thumb and both ankles. She had no associated fever, chills, night sweats, or preceding trauma. There was also no nausea, vomiting, abdominal pain, diarrhea, cough, rhinorrhea, or dysuria. She had no history of rashes, dry mouth, dry eyes, oral or nasal lesions, or other joint pain. She had a history of stroke and glaucoma, and 7 years before presentation, she had undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy for menorrhagia. The patient lived in New England, worked in health care, and was widowed. She was sexually active with one male partner and had had unprotected vaginal intercourse 2 weeks before presentation. She had no pets and did not often spend time outdoors. She did not drink alcohol or use tobacco or illicit drugs. Medications included aspirin and atorvastatin.

On examination, the temperature was 36.6°C, the blood pressure 117/58 mm Hg, the pulse 73 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. She was in no distress and appeared well. The mouth and nose were normal, with no ulcers, and the parotid glands were not enlarged. The first and second heart sounds were normal, with no murmurs. The breath sounds were normal bilaterally, with no wheezing or rhonchi. Bowel sounds were present, and the abdomen was soft, nondistended, and nontender on palpation. The edge of the liver was not palpable, and the spleen was not enlarged. The patient had no rash or telangiectasias. The metacarpophalangeal joint of the right thumb was erythematous and warm, and movement and palpation of the joint caused pain. Effusion of both ankle joints was present, with associated warmth but no erythema. There was pain with dorsiflexion, plantar flexion, eversion, and inversion and on palpation of the ankle joints. The remainder of the examination of the joints was normal.

Blood levels of electrolytes and glucose were normal, as were the results of liver- and renal-function tests. The white-cell count was 13,300 per cubic millimeter (reference range, 4500 to 11,000); the remainder of the complete blood count, including a differential count, was normal. An assay for antinuclear antibodies was positive at a titer of 1:40 with a speckled pattern. Urinalysis by dipstick was normal; examination of the sediment revealed no red cells, no bacteria, and 5 to 10 white cells per high-power field (reference range, 0 to 2). The C-reactive protein level was 47.7 mg per liter (reference range, <8.0), and the erythrocyte sedimentation rate was 62 mm per hour (reference range, 0 to 20).

Radiographs of the ankles and feet showed mild, scattered degenerative changes, with no displaced fractures or dislocations. Radiographs of the right hand showed no fractures or dislocations. A radiograph of the chest showed normal lung volumes, with a normal cardiac silhouette and no focal consolidation, pulmonary edema, or pleural effusions.

The patient was admitted to the hospital, and a diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  A 59-year-old woman was admitted to this hospital because of stiffness, swelling, and severe pain in her right thumb and both ankles.

The patient had been well until 9 days before admission, when stiffness, swelling, and pain developed in the metacarpophalangeal joint of the right thumb that limited her ability to perform tasks such as dressing. The stiffness was not worse in the morning than during the rest of the day, and it did not improve throughout the day. The patient presented to another hospital for evaluation. Radiographs of the hand and wrist were reportedly normal.

Six days before admission, swelling and pain in both ankles developed. The patient was evaluated by her primary care physician, and a 6-day tapering course of oral methylprednisolone was prescribed. After 4 days of methylprednisolone therapy, the joint pain had progressively worsened, and the patient had difficulty walking. She presented to this hospital for evaluation.

On evaluation in the emergency department, the patient reported progressive pain in the right thumb and both ankles. She had no associated fever, chills, night sweats, or preceding trauma. There was also no nausea, vomiting, abdominal pain, diarrhea, cough, rhinorrhea, or dysuria. She had no history of rashes, dry mouth, dry eyes, oral or nasal lesions, or other joint pain. She had a history of stroke and glaucoma, and 7 years before presentation, she had undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy for menorrhagia. The patient lived in New England, worked in health care, and was widowed. She was sexually active with one male partner and had had unprotected vaginal intercourse 2 weeks before presentation. She had no pets and did not often spend time outdoors. She did not drink alcohol or use tobacco or illicit drugs. Medications included aspirin and atorvastatin.

On examination, the temperature was 36.6°C, the blood pressure 117/58 mm Hg, the pulse 73 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. She was in no distress and appeared well. The mouth and nose were normal, with no ulcers, and the parotid glands were not enlarged. The first and second heart sounds were normal, with no murmurs. The breath sounds were normal bilaterally, with no wheezing or rhonchi. Bowel sounds were present, and the abdomen was soft, nondistended, and nontender on palpation. The edge of the liver was not palpable, and the spleen was not enlarged. The patient had no rash or telangiectasias. The metacarpophalangeal joint of the right thumb was erythematous and warm, and movement and palpation of the joint caused pain. Effusion of both ankle joints was present, with associated warmth but no erythema. There was pain with dorsiflexion, plantar flexion, eversion, and inversion and on palpation of the ankle joints. The remainder of the examination of the joints was normal.

Blood levels of electrolytes and glucose were normal, as were the results of liver- and renal-function tests. The white-cell count was 13,300 per cubic millimeter (reference range, 4500 to 11,000); the remainder of the complete blood count, including a differential count, was normal. An assay for antinuclear antibodies was positive at a titer of 1:40 with a speckled pattern. Urinalysis by dipstick was normal; examination of the sediment revealed no red cells, no bacteria, and 5 to 10 white cells per high-power field (reference range, 0 to 2). The C-reactive protein level was 47.7 mg per liter (reference range, <8.0), and the erythrocyte sedimentation rate was 62 mm per hour (reference range, 0 to 20).

Radiographs of the ankles and feet showed mild, scattered degenerative changes, with no displaced fractures or dislocations. Radiographs of the right hand showed no fractures or dislocations. A radiograph of the chest showed normal lung volumes, with a normal cardiac silhouette and no focal consolidation, pulmonary edema, or pleural effusions.

The patient was admitted to the hospital, and a diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Gonococcal arthritis. The patient's symptoms of joint pain and swelling, particularly in the right thumb and both ankles, are indicative of arthritis. The negative results for antinuclear antibodies and normal sedimentation rate suggest that this is not an autoimmune form of arthritis, such as rheumatoid arthritis. The patient's history of unprotected sexual intercourse and the presence of white cells in the urine suggest a sexually transmitted infection, such as gonorrhea, which can cause a disseminated infection leading to arthritis.""
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        ""content"": ""The patient's symptoms of joint pain and swelling in the right thumb and both ankles, along with a high white blood cell count and elevated C-reactive protein and erythrocyte sedimentation rate, suggest an inflammatory process. The lack of improvement with methylprednisolone treatment and the absence of morning stiffness or improvement throughout the day make rheumatoid arthritis less likely. The patient's sexual history and the presence of a few white cells in the urine sediment raise the possibility of a sexually transmitted infection causing reactive arthritis. The positive antinuclear antibody test could be a red herring, as low titers can be seen in healthy individuals and the speckled pattern is not specific for any particular autoimmune disease.\n\nDiagnosis: Reactive arthritis.""
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        ""content"": ""The patient is a 59-year-old woman presenting with stiffness, swelling, and severe pain in her right thumb and both ankles. The differential diagnosis for this patient includes rheumatoid arthritis, osteoarthritis, gout, pseudogout, and infectious arthritis. The patient's symptoms do not improve throughout the day, which is not typical of rheumatoid arthritis, as symptoms usually improve with activity. The patient's radiographs show mild, scattered degenerative changes, which could be indicative of osteoarthritis, but the sudden onset of her symptoms is not typical of this condition. Gout and pseudogout are possibilities, but these conditions usually present with acute, severe pain in one joint, not multiple joints. The patient's elevated white blood cell count and C-reactive protein level suggest an inflammatory or infectious process. The patient's sexual history and the fact that she works in healthcare raise the possibility of a sexually transmitted infection causing infectious arthritis. \n\nDiagnosis: Infectious arthritis, possibly due to a sexually transmitted infection.""
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10.1056/NEJMcpc1706097,Case 28-2017 — A 13-Month-Old Girl with Pneumonia and a 33-Year-Old Woman with Hip Pain,,"Autosomal dominant heterozygous IFN_R1 deficiency.

Disseminated Mycobacterium genavense infection.","CHILD
Disseminated Mycobacterium genavense infection due to an underlying inborn error of interferon-_ immunity.

MOTHER
Disseminated nontuberculous mycobacterial infection, complicated by osteomyelitis, due to an inborn error of interferon-_ immunity.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:            A 13-month-old girl was admitted to this hospital because of pneumonia.

Nine days before admission, fever and vomiting developed in the child. The vomiting resolved after 2 days, but fever (with a maximum temperature of 39.7°C) continued, and the child was fussier than usual. On the fourth day of illness, cough developed. Her parents administered acetaminophen and ibuprofen, but her condition did not improve. On the seventh day of illness, her parents brought her to the emergency department of this hospital for evaluation.

Table 1.

Laboratory Data.
In the emergency department, the parents reported that the child’s appetite had decreased but she had been drinking well and had a normal volume of urine output. On examination, the child was fussy but consolable and appeared mildly ill. The temperature was 37.0°C, the pulse 145 beats per minute, the respiratory rate 32 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The weight was 9.1 kg (46th percentile). Multiple discrete, mobile, mildly enlarged, superficial cervical lymph nodes were present bilaterally; the remainder of the examination was normal. Testing for influenza virus was negative. Urinalysis revealed yellow, slightly cloudy urine, with a specific gravity of 1.017, a pH of 6.0, and 1+ ketones. Blood and urine samples were sent for culture; results of other laboratory tests are shown in Table 1.

Figure 1.

Imaging Studies in the Child.
Dr. Randheer Shailam: Chest radiography revealed dense consolidation of the left upper lobe and, to a lesser extent, the left lower lobe. There was no pleural effusion (Figure 1A).

Dr. Pierce: One dose of ceftriaxone was administered intravenously, and cefdinir was prescribed. The family was advised to follow up with the primary pediatrician 2 days later.

During the next 2 days, fevers persisted despite administration of cefdinir, acetaminophen, and ibuprofen. The cough increased, tachypnea developed, and the use of accessory muscles in the neck and chest was noted. Oral intake and urine output decreased. The child was brought back to the emergency department for evaluation.

The history was obtained from the child’s mother. The child had been born after a full-term gestation. The results of newborn blood-spot screening tests (i.e., a panel of tests for multiple congenital diseases, primarily inborn errors of metabolism) had been normal. The child had been well until 4 months before admission, when a diagnosis of pneumonia was made; she was treated as an outpatient with a 10-day course of an unspecified oral antibiotic agent. Six weeks before admission, she was seen in the emergency department because of vomiting and diarrhea; a diagnosis of viral gastroenteritis was made. Four weeks before admission, she returned to the emergency department because of fever and was again thought to have a viral illness. Three weeks before admission, she received a diagnosis of acute otitis media and was treated with an unspecified oral antibiotic. During the 4 months before admission, the child reportedly did not gain any weight. Medications included acetaminophen, ibuprofen, and cefdinir. She had no known allergies, and immunizations were reportedly current. She was of Brazilian ancestry, was born in New England, and had not traveled. She lived in an urban area of New England with her parents and 5-year-old sister; her mother was a homemaker and her father was a carpenter. The family kept canaries in the home as pets; they had previously had pet cats but not during the 2 months before admission. The child’s maternal grandmother had asthma. In the child’s mother, an ipsilateral axillary mass had developed after she had received the bacille Calmette–Guérin (BCG) vaccine during infancy in Brazil; the mass had been resected, and antibiotics had been administered for many months. While the mother was pregnant with the child, a tuberculin skin test was positive and a chest radiograph was normal.

On examination, the child was in mild respiratory distress. The temperature was 37.8°C, the pulse 193 beats per minute, the respiratory rate 60 breaths per minute, and the oxygen saturation 97% while she was breathing ambient air. The lips were dry. Nasal flaring and suprasternal, intercostal, and subcostal retractions were present. The remainder of the examination was unchanged. Tests for respiratory syncytial virus, adenovirus, parainfluenza virus, and metapneumovirus were negative. A blood sample was sent for culture; other laboratory test results are shown in Table 1. Findings on a chest radiograph appeared unchanged from 2 days earlier. Intravenous fluids, ceftriaxone, azithromycin, and acetaminophen were administered. The child was admitted to the hospital.

During the next 2 days, the administration of intravenous fluids, ceftriaxone, and azithromycin was continued. Fever and cough persisted, and emesis occurred intermittently. On the third hospital day, vancomycin therapy was added. Laboratory tests results are shown in Table 1.

Dr. Shailam: Ultrasonography of the chest was performed, and incidental findings in the spleen prompted extension of the study to include the abdomen and pelvis. The spleen was enlarged and contained numerous hypoechoic lesions measuring up to 1 cm in diameter (Figure 1B). There were multiple enlarged peripancreatic, periportal, and perisplenic lymph nodes, some of which were centrally hypoechoic.

Dr. Pierce: A tuberculin skin test was placed, and airborne precautions were instituted.

Dr. Shailam: The next day, computed tomography of the chest, abdomen, and pelvis was performed after the administration of intravenous contrast material. The findings included left supraclavicular, left hilar, mediastinal, upper abdominal, and mesenteric lymphadenopathy, as well as splenomegaly with multiple hypodense splenic lesions, consolidation with air bronchograms involving the majority of the left upper lobe, scattered pulmonary nodules (measuring 2 to 4 mm in diameter), and narrowing of the left main-stem bronchus due to bulky lymphadenopathy (Figure 1C through 1F).

Dr. Pierce: Azithromycin therapy was discontinued. On the fifth hospital day, bronchoscopy revealed marked external compression of the left main-stem bronchus and left upper lobe and scant secretions in the airways. Bronchoalveolar lavage (BAL) was performed; acid-fast staining of the BAL fluid revealed rare acid-fast bacilli, and a nucleic-acid amplification test for Mycobacterium tuberculosis was negative. Induration (8 mm in diameter) was noted at the site of the tuberculin skin test. Laboratory test results are shown in Table 1. Diagnostic tests were performed, and management decisions were made.

Three months later, the child’s 33-year-old mother was admitted to this hospital because of pain in the right hip. The mother had been well until 6 weeks before admission, when pain in the right groin developed. The pain was initially intermittent and then became more constant, with radiation to the right buttock. She was seen in an urgent care clinic; radiographs of the hip that were obtained during that visit were reportedly normal. A limp developed, and during the 3 weeks before admission, the pain progressed in severity and she began to hold onto objects to support herself as she walked. During this time, she returned to the urgent care clinic and was also seen by her primary care physician. She took ibuprofen, diclofenac, prednisone, and another unspecified medication, but her symptoms did not improve. On the day of admission, the mother presented to the emergency department of this hospital because of progressive pain and difficulty walking.

In the emergency department, the mother reported that no trauma had preceded the onset of pain. She had lost 4.5 kg in weight during the previous 2 months while dieting. She had no fevers, chills, or night sweats. On examination, the vital signs were normal. The gait was antalgic. There was tenderness on palpation of the right hip, and a log-roll test was positive; the active and passive ranges of motion of the right hip were limited by pain. The remainder of the examination was normal. A urinalysis was normal; other laboratory test results are shown in Table 1.

Figure 2.

Imaging Studies in the Mother.
Dr. Shailam: Radiography of the pelvis revealed an ill-defined lytic region in the superior aspect of the right femoral neck (Figure 2A). Magnetic resonance imaging of the right hip, performed with and without the administration of intravenous contrast material, revealed a large lesion at the junction of the right femoral head and neck that had extended through the femoral neck and had caused cortical destruction. There were destructive changes at the femoroacetabular joint, as well as a small joint effusion, exuberant intramuscular edema throughout the upper thigh, markedly enlarged right external and common iliac lymph nodes, and foci of abnormal marrow signal in both iliac wings (Figure 2B through 2F).

Dr. Pierce: Viscous, serosanguineous fluid was aspirated from the right hip joint. Analysis of the synovial fluid revealed a nucleated-cell count of 34 per microliter (reference range, 0 to 200). Gram’s staining, acid-fast staining, and calcofluor white staining of a wet-mount preparation revealed no organisms.

The mother was admitted to the hospital. Additional diagnostic studies were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 13-month-old girl was admitted to this hospital because of pneumonia.

Nine days before admission, fever and vomiting developed in the child. The vomiting resolved after 2 days, but fever (with a maximum temperature of 39.7°C) continued, and the child was fussier than usual. On the fourth day of illness, cough developed. Her parents administered acetaminophen and ibuprofen, but her condition did not improve. On the seventh day of illness, her parents brought her to the emergency department of this hospital for evaluation.

Table 1.

Laboratory Data.
In the emergency department, the parents reported that the child’s appetite had decreased but she had been drinking well and had a normal volume of urine output. On examination, the child was fussy but consolable and appeared mildly ill. The temperature was 37.0°C, the pulse 145 beats per minute, the respiratory rate 32 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The weight was 9.1 kg (46th percentile). Multiple discrete, mobile, mildly enlarged, superficial cervical lymph nodes were present bilaterally; the remainder of the examination was normal. Testing for influenza virus was negative. Urinalysis revealed yellow, slightly cloudy urine, with a specific gravity of 1.017, a pH of 6.0, and 1+ ketones. Blood and urine samples were sent for culture; results of other laboratory tests are shown in Table 1.

Figure 1.

Imaging Studies in the Child.
Dr. Randheer Shailam: Chest radiography revealed dense consolidation of the left upper lobe and, to a lesser extent, the left lower lobe. There was no pleural effusion (Figure 1A).

Dr. Pierce: One dose of ceftriaxone was administered intravenously, and cefdinir was prescribed. The family was advised to follow up with the primary pediatrician 2 days later.

During the next 2 days, fevers persisted despite administration of cefdinir, acetaminophen, and ibuprofen. The cough increased, tachypnea developed, and the use of accessory muscles in the neck and chest was noted. Oral intake and urine output decreased. The child was brought back to the emergency department for evaluation.

The history was obtained from the child’s mother. The child had been born after a full-term gestation. The results of newborn blood-spot screening tests (i.e., a panel of tests for multiple congenital diseases, primarily inborn errors of metabolism) had been normal. The child had been well until 4 months before admission, when a diagnosis of pneumonia was made; she was treated as an outpatient with a 10-day course of an unspecified oral antibiotic agent. Six weeks before admission, she was seen in the emergency department because of vomiting and diarrhea; a diagnosis of viral gastroenteritis was made. Four weeks before admission, she returned to the emergency department because of fever and was again thought to have a viral illness. Three weeks before admission, she received a diagnosis of acute otitis media and was treated with an unspecified oral antibiotic. During the 4 months before admission, the child reportedly did not gain any weight. Medications included acetaminophen, ibuprofen, and cefdinir. She had no known allergies, and immunizations were reportedly current. She was of Brazilian ancestry, was born in New England, and had not traveled. She lived in an urban area of New England with her parents and 5-year-old sister; her mother was a homemaker and her father was a carpenter. The family kept canaries in the home as pets; they had previously had pet cats but not during the 2 months before admission. The child’s maternal grandmother had asthma. In the child’s mother, an ipsilateral axillary mass had developed after she had received the bacille Calmette–Guérin (BCG) vaccine during infancy in Brazil; the mass had been resected, and antibiotics had been administered for many months. While the mother was pregnant with the child, a tuberculin skin test was positive and a chest radiograph was normal.

On examination, the child was in mild respiratory distress. The temperature was 37.8°C, the pulse 193 beats per minute, the respiratory rate 60 breaths per minute, and the oxygen saturation 97% while she was breathing ambient air. The lips were dry. Nasal flaring and suprasternal, intercostal, and subcostal retractions were present. The remainder of the examination was unchanged. Tests for respiratory syncytial virus, adenovirus, parainfluenza virus, and metapneumovirus were negative. A blood sample was sent for culture; other laboratory test results are shown in Table 1. Findings on a chest radiograph appeared unchanged from 2 days earlier. Intravenous fluids, ceftriaxone, azithromycin, and acetaminophen were administered. The child was admitted to the hospital.

During the next 2 days, the administration of intravenous fluids, ceftriaxone, and azithromycin was continued. Fever and cough persisted, and emesis occurred intermittently. On the third hospital day, vancomycin therapy was added. Laboratory tests results are shown in Table 1.

Dr. Shailam: Ultrasonography of the chest was performed, and incidental findings in the spleen prompted extension of the study to include the abdomen and pelvis. The spleen was enlarged and contained numerous hypoechoic lesions measuring up to 1 cm in diameter (Figure 1B). There were multiple enlarged peripancreatic, periportal, and perisplenic lymph nodes, some of which were centrally hypoechoic.

Dr. Pierce: A tuberculin skin test was placed, and airborne precautions were instituted.

Dr. Shailam: The next day, computed tomography of the chest, abdomen, and pelvis was performed after the administration of intravenous contrast material. The findings included left supraclavicular, left hilar, mediastinal, upper abdominal, and mesenteric lymphadenopathy, as well as splenomegaly with multiple hypodense splenic lesions, consolidation with air bronchograms involving the majority of the left upper lobe, scattered pulmonary nodules (measuring 2 to 4 mm in diameter), and narrowing of the left main-stem bronchus due to bulky lymphadenopathy (Figure 1C through 1F).

Dr. Pierce: Azithromycin therapy was discontinued. On the fifth hospital day, bronchoscopy revealed marked external compression of the left main-stem bronchus and left upper lobe and scant secretions in the airways. Bronchoalveolar lavage (BAL) was performed; acid-fast staining of the BAL fluid revealed rare acid-fast bacilli, and a nucleic-acid amplification test for Mycobacterium tuberculosis was negative. Induration (8 mm in diameter) was noted at the site of the tuberculin skin test. Laboratory test results are shown in Table 1. Diagnostic tests were performed, and management decisions were made.

Three months later, the child’s 33-year-old mother was admitted to this hospital because of pain in the right hip. The mother had been well until 6 weeks before admission, when pain in the right groin developed. The pain was initially intermittent and then became more constant, with radiation to the right buttock. She was seen in an urgent care clinic; radiographs of the hip that were obtained during that visit were reportedly normal. A limp developed, and during the 3 weeks before admission, the pain progressed in severity and she began to hold onto objects to support herself as she walked. During this time, she returned to the urgent care clinic and was also seen by her primary care physician. She took ibuprofen, diclofenac, prednisone, and another unspecified medication, but her symptoms did not improve. On the day of admission, the mother presented to the emergency department of this hospital because of progressive pain and difficulty walking.

In the emergency department, the mother reported that no trauma had preceded the onset of pain. She had lost 4.5 kg in weight during the previous 2 months while dieting. She had no fevers, chills, or night sweats. On examination, the vital signs were normal. The gait was antalgic. There was tenderness on palpation of the right hip, and a log-roll test was positive; the active and passive ranges of motion of the right hip were limited by pain. The remainder of the examination was normal. A urinalysis was normal; other laboratory test results are shown in Table 1.

Figure 2.

Imaging Studies in the Mother.
Dr. Shailam: Radiography of the pelvis revealed an ill-defined lytic region in the superior aspect of the right femoral neck (Figure 2A). Magnetic resonance imaging of the right hip, performed with and without the administration of intravenous contrast material, revealed a large lesion at the junction of the right femoral head and neck that had extended through the femoral neck and had caused cortical destruction. There were destructive changes at the femoroacetabular joint, as well as a small joint effusion, exuberant intramuscular edema throughout the upper thigh, markedly enlarged right external and common iliac lymph nodes, and foci of abnormal marrow signal in both iliac wings (Figure 2B through 2F).

Dr. Pierce: Viscous, serosanguineous fluid was aspirated from the right hip joint. Analysis of the synovial fluid revealed a nucleated-cell count of 34 per microliter (reference range, 0 to 200). Gram’s staining, acid-fast staining, and calcofluor white staining of a wet-mount preparation revealed no organisms.

The mother was admitted to the hospital. Additional diagnostic studies were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Disseminated Mycobacterium bovis infection. \n\nThe child presents with a history of recurrent infections, including pneumonia, otitis media, and gastroenteritis, as well as failure to thrive. The mother has a history of a positive tuberculin skin test and an axillary mass following BCG vaccination. The child's imaging shows consolidation in the lungs, splenomegaly with hypoechoic lesions, and lymphadenopathy. The mother's imaging shows a lytic lesion in the femur and enlarged iliac lymph nodes. These findings suggest a systemic infection with a mycobacterium, likely M. bovis given the mother's history of BCG vaccination and the child's negative nucleic-acid amplification test for M. tuberculosis.""
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10.1056/NEJMcpc1706111,Case 27-2017 — A 32-Year-Old Man with Acute Chest Pain,,Acute and chronic cholecystitis and extensive cholelithiasis with transmural gallbladder inflammation.,Biliary pain due to cholecystitis or choledocholithiasis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:        A 32-year-old man was evaluated in the emergency department of this hospital for the abrupt onset of postprandial chest pain.

Several hours before presentation, the patient had eaten pizza in his apartment. Less than 1 hour later, while he was at rest and watching television, “crushing” pain, diaphoresis, dyspnea, and nausea developed. He rated the pain at 7 on a scale of 0 to 10 (with 10 indicating the most severe pain), and he noted that the pain did not radiate or worsen with respiration. He attempted to induce vomiting and took calcium carbonate tablets, but his condition did not improve. After 2 hours of constant pain, he presented to the emergency department of this hospital.

The patient had no medical history and took no medications. His father had had a myocardial infarction when he was 51 years of age. The patient was allergic to penicillin (unknown reaction). He lived with his girlfriend, who had recently had streptococcal pharyngitis. He had been under a great deal of stress because of a new job as a sales manager, a move to a new apartment, and the recent death of a family pet. He consumed a six-pack of beer daily. He had used cocaine (most recently 3 months earlier) but did not report using other illicit substances.

On examination, the temperature was 36.3°C, the heart rate 83 beats per minute, the blood pressure 158/81 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 26.9. He appeared to be anxious and uncomfortable and had diaphoresis. The jugular venous pressure was 6 cm of water with a normal waveform. There was no evidence of a heart murmur or rub. When the patient was asked to indicate the location of the pain, he pointed to the subxiphoid area; there was some tenderness in that area on palpation. The stool was guaiac negative. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Figure 1.

Electrocardiogram.
Urinalysis revealed a specific gravity of greater than 1.040 and was otherwise normal. A urine toxicology screen revealed cannabinoids, and a blood toxicology screen was negative; other laboratory test results are shown in Table 1. An electrocardiogram showed concave ST-segment elevations (1 to 2 mm) in the inferior leads and V3 through V6 precordial leads, along with a PR-segment elevation in lead aVR and possible subtle PR-segment depressions (Figure 1). Imaging studies were obtained.

Dr. Matthew P. Moy: A chest radiograph was normal. The lungs were clear, and there was no evidence of pneumothorax, cardiomegaly, or mediastinal widening.

Dr. Dudzinski: Aspirin, clopidogrel, intravenous morphine sulfate, lorazepam, ranitidine, aluminum hydroxide–diphenhydramine–lidocaine–magnesium hydroxide, and intravenous infusions of heparin and nitroglycerin were administered, and emergency coronary angiography was arranged. A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:           A 32-year-old man was evaluated in the emergency department of this hospital for the abrupt onset of postprandial chest pain.

Several hours before presentation, the patient had eaten pizza in his apartment. Less than 1 hour later, while he was at rest and watching television, “crushing” pain, diaphoresis, dyspnea, and nausea developed. He rated the pain at 7 on a scale of 0 to 10 (with 10 indicating the most severe pain), and he noted that the pain did not radiate or worsen with respiration. He attempted to induce vomiting and took calcium carbonate tablets, but his condition did not improve. After 2 hours of constant pain, he presented to the emergency department of this hospital.

The patient had no medical history and took no medications. His father had had a myocardial infarction when he was 51 years of age. The patient was allergic to penicillin (unknown reaction). He lived with his girlfriend, who had recently had streptococcal pharyngitis. He had been under a great deal of stress because of a new job as a sales manager, a move to a new apartment, and the recent death of a family pet. He consumed a six-pack of beer daily. He had used cocaine (most recently 3 months earlier) but did not report using other illicit substances.

On examination, the temperature was 36.3°C, the heart rate 83 beats per minute, the blood pressure 158/81 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 26.9. He appeared to be anxious and uncomfortable and had diaphoresis. The jugular venous pressure was 6 cm of water with a normal waveform. There was no evidence of a heart murmur or rub. When the patient was asked to indicate the location of the pain, he pointed to the subxiphoid area; there was some tenderness in that area on palpation. The stool was guaiac negative. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Figure 1.

Electrocardiogram.
Urinalysis revealed a specific gravity of greater than 1.040 and was otherwise normal. A urine toxicology screen revealed cannabinoids, and a blood toxicology screen was negative; other laboratory test results are shown in Table 1. An electrocardiogram showed concave ST-segment elevations (1 to 2 mm) in the inferior leads and V3 through V6 precordial leads, along with a PR-segment elevation in lead aVR and possible subtle PR-segment depressions (Figure 1). Imaging studies were obtained.

Dr. Matthew P. Moy: A chest radiograph was normal. The lungs were clear, and there was no evidence of pneumothorax, cardiomegaly, or mediastinal widening.

Dr. Dudzinski: Aspirin, clopidogrel, intravenous morphine sulfate, lorazepam, ranitidine, aluminum hydroxide–diphenhydramine–lidocaine–magnesium hydroxide, and intravenous infusions of heparin and nitroglycerin were administered, and emergency coronary angiography was arranged. A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Acute Myocardial Infarction. The patient's symptoms of crushing chest pain, diaphoresis, dyspnea, and nausea are classic symptoms of a heart attack. The fact that the pain did not improve with attempts to induce vomiting or taking calcium carbonate tablets, which might alleviate symptoms of heartburn or indigestion, further supports this diagnosis. The patient's father's history of myocardial infarction at a relatively young age suggests a possible genetic predisposition. The patient's heavy alcohol consumption and past cocaine use are risk factors for coronary artery disease. The electrocardiogram findings of ST-segment elevations are consistent with acute myocardial infarction.""
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        ""content"": ""The patient's symptoms of crushing chest pain, diaphoresis, dyspnea, and nausea are classic symptoms of myocardial infarction. The fact that the pain did not improve with attempts to induce vomiting or taking calcium carbonate tablets, which would typically alleviate symptoms of gastrointestinal distress, further supports a cardiac origin of the pain. The patient's father's history of myocardial infarction at a relatively young age suggests a possible genetic predisposition to heart disease. The patient's daily alcohol consumption and past cocaine use are both risk factors for heart disease. The electrocardiogram findings of ST-segment elevations are indicative of acute myocardial infarction. The fact that the patient's symptoms began after eating pizza, a high-fat meal, could suggest that the meal triggered the event by causing a sudden increase in demand on the heart. \n\nDiagnosis: Acute Myocardial Infarction""
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        ""content"": ""The patient is a 32-year-old male presenting with sudden onset of postprandial chest pain, diaphoresis, dyspnea, and nausea. The differential diagnosis for this patient includes acute coronary syndrome (ACS), gastroesophageal reflux disease (GERD), peptic ulcer disease, and esophageal spasm. The patient's symptoms started after eating pizza, which could suggest GERD or peptic ulcer disease. However, the severity of the pain and associated symptoms of diaphoresis and dyspnea are more suggestive of a cardiac etiology. The patient's father had a myocardial infarction at a relatively young age, which increases the patient's risk for coronary artery disease. The patient's heavy alcohol use and past cocaine use are also risk factors for ACS. The patient's EKG shows ST-segment elevations, which is indicative of myocardial injury and supports the diagnosis of ACS. The patient's chest pain did not improve with attempts to induce vomiting or taking calcium carbonate tablets, which would be expected to help if the cause was GERD or peptic ulcer disease. The patient's chest radiograph was normal, which makes a pulmonary cause of the patient's symptoms less likely. \n\nDiagnosis: Acute coronary syndrome.""
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10.1056/NEJMcpc1616402,"Case 26-2017 — A 63-Year-Old Woman with Fever, Hypotension, and Hypoxemia",,Cytomegalovirus pneumonitis.,Cytomegalovirus infection complicated by pneumonitis and pancytopenia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:             A 63-year-old woman was admitted to the intensive care unit (ICU) of this hospital because of fever, hypotension, and hypoxemia.

Five months before the current admission, weakness of the proximal muscles of the arms and dyspnea on exertion developed in the patient. One month later, she was admitted to this hospital with worsening symptoms. Follicular erythematous papules were present on the lateral aspect of both hips, and the blood creatine kinase level was 1856 U per liter (reference range, 40 to 150).

A skin biopsy of the lesions on the lateral hips revealed interface dermatitis. A diagnosis of dermatomyositis was made. An interferon-_ release assay for Mycobacterium tuberculosis was negative, and treatment with prednisone and azathioprine was initiated, along with trimethoprim–sulfamethoxazole for prophylaxis against Pneumocystis jirovecii pneumonia. An extensive evaluation for cancer — including mammography, computed tomography (CT) of the abdomen and pelvis, transvaginal ultrasonography, colonoscopy, and a Papanicolaou smear — was unrevealing. After the initiation of prednisone and azathioprine therapy, the blood creatine kinase level decreased to 683 U per liter, and the patient had a temporary mild increase in strength.

Despite the initial improvement of the patient’s symptoms, the proximal muscle weakness gradually worsened and the blood creatine kinase level increased during the next several weeks. Dyspnea on exertion progressed, and when the patient was chewing, she noted fatigue in the muscles of her jaw and neck. Three months before the current admission, the patient was evaluated by her rheumatologist and reported severe dyspnea at rest. She was readmitted to this hospital for further evaluation, and additional imaging studies were obtained.

Figure 1.

CT Scan of the Chest Obtained 3 Months before Admission.
Dr. Melissa C. Price: CT of the chest was performed during expiration and after the administration of intravenous contrast material. Bilateral ground-glass opacities in a mosaic distribution were present, and there was no consolidation (Figure 1).

Dr. Goldstein: To further assess the worsening dyspnea on exertion and the abnormalities seen on imaging studies of the chest, pulmonary-function testing was performed. The forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and ratio of FEV1 to FVC were normal, as were the total lung capacity, carbon monoxide diffusing capacity, and maximal respiratory muscle strength.

The patient reported difficulty swallowing, and a diagnosis of aspiration was considered. A video swallow study showed only mild oropharyngeal dysphagia and no evidence of aspiration.

Because the patient had ongoing proximal muscle weakness despite treatment for dermatomyositis, a diagnosis of glucocorticoid-induced myopathy was considered and additional testing was performed. Needle electromyography revealed abnormal spontaneous activity that was suggestive of ongoing muscle injury in the left deltoid and left vastus lateralis muscles, and magnetic resonance imaging of the left leg revealed extensive muscle edema and enhancement that were consistent with myositis, as well as focal nonenhancing areas that were suggestive of necrosis.

Despite treatment with high-dose methylprednisolone and intravenous immune globulin (IVIG), the proximal muscle weakness and dyspnea persisted. Treatment with rituximab was initiated. The proximal muscle weakness and dyspnea diminished, and on hospital day 10, the patient was discharged; prednisone and azathioprine were continued. Three weeks later, she was evaluated by her rheumatologist and reported improvement in her weakness and dyspnea; the dose of prednisone was tapered from 60 mg to 40 mg daily.

One month before the current admission, dysphagia increased and new weakness of the distal muscles of the arms developed in the patient. Repeat electromyography of the arms revealed persistent myopathy in the proximal muscles and new myopathy in the distal muscles. A muscle biopsy was performed. Pathological evaluation of a biopsy specimen of the right quadriceps muscle revealed an active inflammatory myopathy, and electron microscopy revealed tubuloreticular inclusions in endothelial cells, a finding supportive of the diagnosis of dermatomyositis. The dose of prednisone was increased, and the patient was again treated with IVIG.

On the day of the current admission to this hospital, the patient was seen in the rheumatology clinic and then referred to the emergency department for evaluation because of a 2-day history of increasing fatigue, chills, night sweats, increased dysphagia, and a new productive cough. The patient reported no dysuria, diarrhea, abdominal pain, or headache. She had a history of glaucoma and hypothyroidism. Ten years earlier, she had been treated with a 6-month course of isoniazid for latent tuberculosis, which had been diagnosed with the use of tuberculin skin testing. In addition to prednisone and azathioprine, her medications included levothyroxine, liothyronine, and a multivitamin. She had received the last infusion of rituximab 10 weeks earlier. Her mother had myasthenia gravis, and multiple family members had had lung cancer. She worked as a health care provider, lived in New England, and had traveled to California but not outside the United States.

Table 1.

Laboratory Data.
On examination, the temperature was 39.3°C, the blood pressure 85/47 mm Hg, the pulse 90 beats per minute, the respiratory rate 32 breaths per minute, and the oxygen saturation 87% while the patient was breathing ambient air. Supplemental oxygen was delivered through a nasal cannula at a rate of 3 to 6 liters per minute, with adjustment to keep the oxygen saturation above 93%. The patient was awake and alert but appeared generally unwell. The first and second heart sounds were normal, without murmurs, and there was no jugular venous distention. Crackles were present in the lower lung fields. Bowel sounds were present, and the abdomen was soft, nondistended, and nontender on palpation. The liver and spleen were not palpable. The arms and legs had no edema, and muscle bulk was diffusely decreased. Strength was symmetric and graded as 4 out of 5 in the proximal and distal muscles of the arms, 4 out of 5 in the proximal muscles of the legs, and 5 out of 5 in the distal muscles of the legs. Deep-tendon reflexes were diffusely hypoactive in the arms and knees and normal at the ankles. Cultures of urine and blood had no growth. Testing of a nasal swab for influenza A and B nucleic acids was negative. A screening test for human immunodeficiency virus (HIV) type 1 p24 antigen and HIV type 1 and type 2 antibodies was negative; other laboratory test results are shown in Table 1. A chest radiograph showed a patchy linear opacity at the base of the left lung. Intravenous fluids, high-dose methylprednisolone, vancomycin, and cefepime were administered, and the patient was admitted to the ICU while she received a continuous infusion of norepinephrine. Azathioprine was discontinued, and atovaquone was substituted for trimethoprim–sulfamethoxazole.

The blood pressure improved. Norepinephrine and methylprednisolone were discontinued, prednisone was resumed, and the patient was transferred to the medical unit. Vancomycin and cefepime were continued. The patient’s need for supplemental oxygen to maintain 93% saturation varied from 1 liter delivered through a nasal cannula to 10 liters delivered through a face tent. Additional imaging studies were obtained.

Figure 2.

CT Scan of the Chest Obtained On Admission.
Dr. Price: CT of the chest, performed without the administration of intravenous contrast material, revealed new consolidations in the dependent portion of the bilateral lower lobes and inferior lingula. In addition, new interlobular septal thickening, bilateral ground-glass opacities, and trace bilateral pleural effusions were present. Subpleural reticulations were seen in the lower lobes. There was no intrathoracic lymphadenopathy (Figure 2).

Dr. Goldstein: A repeat video swallow study was obtained on hospital day 8 because of concerns about possible aspiration pneumonia. There was moderate oropharyngeal dysphagia and intermittent trace aspiration.

The patient had no fever for 3 days, but on hospital day 5, the temperature rose to 39.6°C. During the next 3 days, high temperatures persisted despite continued treatment with vancomycin and cefepime. Cultures of urine and blood were sterile; other laboratory test results are shown in Table 1. Diagnostic tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 63-year-old woman was admitted to the intensive care unit (ICU) of this hospital because of fever, hypotension, and hypoxemia.

Five months before the current admission, weakness of the proximal muscles of the arms and dyspnea on exertion developed in the patient. One month later, she was admitted to this hospital with worsening symptoms. Follicular erythematous papules were present on the lateral aspect of both hips, and the blood creatine kinase level was 1856 U per liter (reference range, 40 to 150).

A skin biopsy of the lesions on the lateral hips revealed interface dermatitis. A diagnosis of dermatomyositis was made. An interferon-_ release assay for Mycobacterium tuberculosis was negative, and treatment with prednisone and azathioprine was initiated, along with trimethoprim–sulfamethoxazole for prophylaxis against Pneumocystis jirovecii pneumonia. An extensive evaluation for cancer — including mammography, computed tomography (CT) of the abdomen and pelvis, transvaginal ultrasonography, colonoscopy, and a Papanicolaou smear — was unrevealing. After the initiation of prednisone and azathioprine therapy, the blood creatine kinase level decreased to 683 U per liter, and the patient had a temporary mild increase in strength.

Despite the initial improvement of the patient’s symptoms, the proximal muscle weakness gradually worsened and the blood creatine kinase level increased during the next several weeks. Dyspnea on exertion progressed, and when the patient was chewing, she noted fatigue in the muscles of her jaw and neck. Three months before the current admission, the patient was evaluated by her rheumatologist and reported severe dyspnea at rest. She was readmitted to this hospital for further evaluation, and additional imaging studies were obtained.

Figure 1.

CT Scan of the Chest Obtained 3 Months before Admission.
Dr. Melissa C. Price: CT of the chest was performed during expiration and after the administration of intravenous contrast material. Bilateral ground-glass opacities in a mosaic distribution were present, and there was no consolidation (Figure 1).

Dr. Goldstein: To further assess the worsening dyspnea on exertion and the abnormalities seen on imaging studies of the chest, pulmonary-function testing was performed. The forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and ratio of FEV1 to FVC were normal, as were the total lung capacity, carbon monoxide diffusing capacity, and maximal respiratory muscle strength.

The patient reported difficulty swallowing, and a diagnosis of aspiration was considered. A video swallow study showed only mild oropharyngeal dysphagia and no evidence of aspiration.

Because the patient had ongoing proximal muscle weakness despite treatment for dermatomyositis, a diagnosis of glucocorticoid-induced myopathy was considered and additional testing was performed. Needle electromyography revealed abnormal spontaneous activity that was suggestive of ongoing muscle injury in the left deltoid and left vastus lateralis muscles, and magnetic resonance imaging of the left leg revealed extensive muscle edema and enhancement that were consistent with myositis, as well as focal nonenhancing areas that were suggestive of necrosis.

Despite treatment with high-dose methylprednisolone and intravenous immune globulin (IVIG), the proximal muscle weakness and dyspnea persisted. Treatment with rituximab was initiated. The proximal muscle weakness and dyspnea diminished, and on hospital day 10, the patient was discharged; prednisone and azathioprine were continued. Three weeks later, she was evaluated by her rheumatologist and reported improvement in her weakness and dyspnea; the dose of prednisone was tapered from 60 mg to 40 mg daily.

One month before the current admission, dysphagia increased and new weakness of the distal muscles of the arms developed in the patient. Repeat electromyography of the arms revealed persistent myopathy in the proximal muscles and new myopathy in the distal muscles. A muscle biopsy was performed. Pathological evaluation of a biopsy specimen of the right quadriceps muscle revealed an active inflammatory myopathy, and electron microscopy revealed tubuloreticular inclusions in endothelial cells, a finding supportive of the diagnosis of dermatomyositis. The dose of prednisone was increased, and the patient was again treated with IVIG.

On the day of the current admission to this hospital, the patient was seen in the rheumatology clinic and then referred to the emergency department for evaluation because of a 2-day history of increasing fatigue, chills, night sweats, increased dysphagia, and a new productive cough. The patient reported no dysuria, diarrhea, abdominal pain, or headache. She had a history of glaucoma and hypothyroidism. Ten years earlier, she had been treated with a 6-month course of isoniazid for latent tuberculosis, which had been diagnosed with the use of tuberculin skin testing. In addition to prednisone and azathioprine, her medications included levothyroxine, liothyronine, and a multivitamin. She had received the last infusion of rituximab 10 weeks earlier. Her mother had myasthenia gravis, and multiple family members had had lung cancer. She worked as a health care provider, lived in New England, and had traveled to California but not outside the United States.

Table 1.

Laboratory Data.
On examination, the temperature was 39.3°C, the blood pressure 85/47 mm Hg, the pulse 90 beats per minute, the respiratory rate 32 breaths per minute, and the oxygen saturation 87% while the patient was breathing ambient air. Supplemental oxygen was delivered through a nasal cannula at a rate of 3 to 6 liters per minute, with adjustment to keep the oxygen saturation above 93%. The patient was awake and alert but appeared generally unwell. The first and second heart sounds were normal, without murmurs, and there was no jugular venous distention. Crackles were present in the lower lung fields. Bowel sounds were present, and the abdomen was soft, nondistended, and nontender on palpation. The liver and spleen were not palpable. The arms and legs had no edema, and muscle bulk was diffusely decreased. Strength was symmetric and graded as 4 out of 5 in the proximal and distal muscles of the arms, 4 out of 5 in the proximal muscles of the legs, and 5 out of 5 in the distal muscles of the legs. Deep-tendon reflexes were diffusely hypoactive in the arms and knees and normal at the ankles. Cultures of urine and blood had no growth. Testing of a nasal swab for influenza A and B nucleic acids was negative. A screening test for human immunodeficiency virus (HIV) type 1 p24 antigen and HIV type 1 and type 2 antibodies was negative; other laboratory test results are shown in Table 1. A chest radiograph showed a patchy linear opacity at the base of the left lung. Intravenous fluids, high-dose methylprednisolone, vancomycin, and cefepime were administered, and the patient was admitted to the ICU while she received a continuous infusion of norepinephrine. Azathioprine was discontinued, and atovaquone was substituted for trimethoprim–sulfamethoxazole.

The blood pressure improved. Norepinephrine and methylprednisolone were discontinued, prednisone was resumed, and the patient was transferred to the medical unit. Vancomycin and cefepime were continued. The patient’s need for supplemental oxygen to maintain 93% saturation varied from 1 liter delivered through a nasal cannula to 10 liters delivered through a face tent. Additional imaging studies were obtained.

Figure 2.

CT Scan of the Chest Obtained On Admission.
Dr. Price: CT of the chest, performed without the administration of intravenous contrast material, revealed new consolidations in the dependent portion of the bilateral lower lobes and inferior lingula. In addition, new interlobular septal thickening, bilateral ground-glass opacities, and trace bilateral pleural effusions were present. Subpleural reticulations were seen in the lower lobes. There was no intrathoracic lymphadenopathy (Figure 2).

Dr. Goldstein: A repeat video swallow study was obtained on hospital day 8 because of concerns about possible aspiration pneumonia. There was moderate oropharyngeal dysphagia and intermittent trace aspiration.

The patient had no fever for 3 days, but on hospital day 5, the temperature rose to 39.6°C. During the next 3 days, high temperatures persisted despite continued treatment with vancomycin and cefepime. Cultures of urine and blood were sterile; other laboratory test results are shown in Table 1. Diagnostic tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Pneumocystis jirovecii pneumonia (PJP)\n\nThe patient's history of dermatomyositis, a systemic autoimmune disease, and her treatment with immunosuppressive drugs such as prednisone, azathioprine, and rituximab, put her at risk for opportunistic infections. Her symptoms of fever, hypotension, and hypoxemia, along with the presence of bilateral ground-glass opacities on CT scan, are suggestive of pneumonia. The fact that her symptoms did not improve with broad-spectrum antibiotics (vancomycin and cefepime) suggests an atypical pathogen. PJP is a common opportunistic infection in immunocompromised patients and often presents with ground-glass opacities on imaging. The patient was initially on trimethoprim-sulfamethoxazole for PJP prophylaxis, but this was switched to atovaquone, which may have been less effective.""
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        ""content"": ""The patient's history of dermatomyositis, a condition that can cause muscle weakness and skin changes, is important. The patient's symptoms of fever, hypotension, and hypoxemia suggest a possible infection. The patient's history of immunosuppressive therapy with prednisone, azathioprine, and rituximab increases her risk for opportunistic infections. The patient's CT scan shows new consolidations in the dependent portion of the bilateral lower lobes and inferior lingula, new interlobular septal thickening, bilateral ground-glass opacities, and trace bilateral pleural effusions, which are suggestive of pneumonia. The patient's fever persisted despite treatment with broad-spectrum antibiotics, suggesting that the causative organism may be resistant to these antibiotics or that the patient has an opportunistic infection that is not covered by these antibiotics. The patient's history of latent tuberculosis treated with isoniazid is also important, as reactivation of tuberculosis can occur in immunosuppressed patients. However, the patient's negative interferon-_ release assay for Mycobacterium tuberculosis makes this less likely. The patient's moderate oropharyngeal dysphagia and intermittent trace aspiration seen on the video swallow study suggest the possibility of aspiration pneumonia. \n\nDiagnosis: Aspiration pneumonia.""
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        ""content"": ""This is a 63-year-old woman with a history of dermatomyositis who presents with fever, hypotension, and hypoxemia. She has been on immunosuppressive therapy with prednisone and azathioprine, and has recently been treated with rituximab. Her symptoms include increasing fatigue, chills, night sweats, increased dysphagia, and a new productive cough. The differential diagnosis for this patient includes bacterial pneumonia, aspiration pneumonia, Pneumocystis jirovecii pneumonia, and other opportunistic infections due to her immunosuppressed state. The patient's CT scan shows new consolidations in the dependent portion of the bilateral lower lobes and inferior lingula, new interlobular septal thickening, bilateral ground-glass opacities, and trace bilateral pleural effusions. These findings are suggestive of an infectious process. The patient's fever persists despite treatment with vancomycin and cefepime, suggesting that the causative organism may be resistant to these antibiotics, or that a non-bacterial pathogen may be responsible. Given the patient's immunosuppressed state, her prophylaxis with trimethoprim-sulfamethoxazole, and the ground-glass opacities seen on imaging, Pneumocystis jirovecii pneumonia is a strong possibility. \n\nDiagnosis: Pneumocystis jirovecii pneumonia.""
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10.1056/NEJMcpc1706099,"Case 25-2017 — A 45-Year-Old Man with Headache, Fever, and Lymphadenopathy",,Atypical immunoblastic reaction that was consistent with primary Epstein–Barr virus infection.,Acute Epstein–Barr virus infection (infectious mononucleosis).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                    A 45-year-old man with Tourette’s syndrome and a ventriculoperitoneal shunt for the management of hydrocephalus was admitted to this hospital because of headache and fever.

The patient had been well until 3 days before admission, when he awoke with a severe, diffuse, pounding headache. He noted that the pain was similar to pain he had had in association with the malfunction of a ventriculoperitoneal shunt 24 years earlier. The patient took ibuprofen but had no symptom relief. Fevers, anorexia, fatigue, and mild nausea also developed. The evening before admission, he presented to the emergency department of another hospital for evaluation.

Table 1.

Laboratory Data.
On evaluation, the patient rated his headache as 8 on a scale of 0 to 10 (with 10 indicating the most severe pain). On examination, the temperature was 37.6°C, the pulse 88 beats per minute, the blood pressure 96/56 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. He appeared well, and the findings on a general physical examination were normal. Laboratory test results are shown in Table 1. Imaging studies were obtained.

Dr. Efren J. Flores: Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed the presence of a right frontal ventriculoperitoneal shunt, which tunneled across the vertex and inferiorly down the left side of the scalp, without an apparent reservoir, and terminated just superior to the third ventricle. There was no evidence of hydrocephalus; the frontal horns of the lateral ventricles were not apparent, and the right lateral ventricle had a prominent temporal horn that abutted a region of temporo-occipital hypodensity and encephalomalacia. In addition, a series of radiographs, which were obtained to assess the position and function of the ventriculoperitoneal shunt, revealed several remnants of the shunt catheter in the left thorax, as well as a large mass in the right hilum.

Dr. Adelman: Acetaminophen was administered orally, and normal saline, fentanyl, and ondansetron were administered intravenously. The following day, the patient was transferred by ambulance to the emergency department of this hospital for further treatment.

While the patient was in the ambulance, his temperature rose to 39.2°C and the headache persisted. Morphine was administered. On arrival in the emergency department, the patient reported that the severity of his headache had decreased. Several weeks earlier, he had not passed an eye examination for a driver’s license because of poor peripheral vision. He had Tourette’s syndrome and a cyst of the posterior fossa that was associated with hydrocephalus, which had been managed with ventriculoperitoneal shunting since childhood. He had undergone five shunt revisions; the most recent had been performed 24 years earlier because of shunt malfunction. He took no medications and had no known allergies. He lived with his girlfriend in New England, where he was employed in the shipbuilding industry; he enjoyed spending time outdoors and worked part-time as a nature guide. He was monogamous with his girlfriend, drank an average of four beers weekly, and did not use tobacco or illicit drugs. He had not recently traveled outside New England and had no known exposure to sick persons or tick bites. There was no family history of cancer.

On examination, the temperature was 39.2°C, the pulse 81 beats per minute, the blood pressure 121/79 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air. Left homonymous hemianopsia was present; the remainder of the general examination was unchanged. Laboratory test results are shown in Table 1.

Morphine and lorazepam were administered intravenously, and a lumbar puncture was performed with the patient in the left lateral decubitus position. The opening pressure was 24 cm of water, and the cerebrospinal fluid was clear and colorless, with a protein level of 124 mg per deciliter (reference range, 5 to 55) and a glucose level of 49 mg per deciliter (2.7 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]) and with three nucleated cells and no blood cells per microliter. Gram’s staining did not reveal any microorganisms; a specimen was sent for bacterial culture. Other laboratory test results are shown in Table 1. Blood cultures were obtained, and vancomycin, ceftriaxone, and acyclovir were administered intravenously. The patient was admitted to the hospital.

On physical examination the following morning, nontender lymphadenopathy was noted in the cervical, postauricular, supraclavicular, axillary, and inguinal regions. The spleen was not enlarged, and the temperature ranged from 36.4°C to 38.0°C. The examination was otherwise unchanged. Laboratory test results are shown in Table 1. Urinalysis revealed cloudy, amber urine, with a specific gravity of 1.017, a pH of 5.0, and 2+ urobilinogen by dipstick. Examination of a peripheral-blood smear for parasites was negative. Additional imaging studies were obtained.

Figure 1.

Imaging Studies.
Dr. Flores: Abdominal ultrasonography revealed several well-circumscribed, avascular, hypoechoic lesions abutting the pancreatic head that were thought to represent enlarged lymph nodes, as well as an exophytic, hypoechoic lesion (2 cm in diameter) at the lower pole of the left kidney. A single-view radiograph of the chest (Figure 1A) showed a fragmented ventriculoperitoneal shunt catheter on the left side. In addition, there was widening of the mediastinum and bilateral hilar nodular thickening. These findings are consistent with underlying mediastinal and bilateral hilar lymphadenopathy.

Subsequently, CT scans of the chest, abdomen, and pelvis were performed after the administration of oral and intravenous contrast material (Figure 1B through 1G). Axial images of the chest obtained with a soft-tissue window setting showed mediastinal lymphadenopathy involving several nodal stations, including the prevascular, aortopulmonary, right paratracheal, and right lower paratracheal regions. Images of the chest obtained with the lung window setting showed volume loss of the right middle lobe and atelectasis due to right hilar lymphadenopathy, which partially narrows the bronchus intermedius and partially obstructs the bronchus of the right middle lobe. A coronal image of the abdomen and pelvis obtained with a soft-tissue window setting showed extensive retroperitoneal and left inguinal lymphadenopathy, and axial images showed retroperitoneal and left external iliac lymphadenopathy and infiltrative left renal lesions.

Dr. Adelman: Vancomycin, ceftriaxone, and acyclovir were stopped. The headache persisted, and fevers continued. Morphine and acetaminophen were administered, and the patient had symptom relief.

On the third hospital day, the patient continued to feel unwell and had night sweats. Fevers to a temperature of 38.3°C continued. Laboratory test results are shown in Table 1. Manual review of the peripheral-blood smear by a hematopathologist was requested, and flow cytometry was performed.

Figure 2.

Peripheral-Blood Smear and Flow Cytometry.
Dr. Aliyah R. Sohani: Examination of the peripheral-blood smear (Figure 2A, 2B, and 2C) revealed atypical polymorphous lymphoid cells with round-to-irregular nuclei, some with nucleoli, and moderate-to-abundant cytoplasm; a few cytoplasmic granules were present in some of the cells. Plasmacytoid lymphocytes and occasional plasma cells were also present; no blasts were seen. Some neutrophils appeared to be hypogranulated, and large platelets were present. Flow cytometry of the peripheral blood revealed a differential count of 35% lymphocytes, 6% monocytes, and 54% granulocytes, as well as 3% polyclonal B cells, 27% CD3+ T cells (with no immunophenotypic abnormalities), 4% natural killer (NK) cells, 1.5% CD3+CD16+CD57+CD8+ T cells, and no myeloid or lymphoid blasts. There was a markedly inverted ratio of CD4 cells to CD8 cells of 0.08 (Figure 2D).

Dr. Adelman: Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                A 45-year-old man with Tourette’s syndrome and a ventriculoperitoneal shunt for the management of hydrocephalus was admitted to this hospital because of headache and fever.

The patient had been well until 3 days before admission, when he awoke with a severe, diffuse, pounding headache. He noted that the pain was similar to pain he had had in association with the malfunction of a ventriculoperitoneal shunt 24 years earlier. The patient took ibuprofen but had no symptom relief. Fevers, anorexia, fatigue, and mild nausea also developed. The evening before admission, he presented to the emergency department of another hospital for evaluation.

Table 1.

Laboratory Data.
On evaluation, the patient rated his headache as 8 on a scale of 0 to 10 (with 10 indicating the most severe pain). On examination, the temperature was 37.6°C, the pulse 88 beats per minute, the blood pressure 96/56 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. He appeared well, and the findings on a general physical examination were normal. Laboratory test results are shown in Table 1. Imaging studies were obtained.

Dr. Efren J. Flores: Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed the presence of a right frontal ventriculoperitoneal shunt, which tunneled across the vertex and inferiorly down the left side of the scalp, without an apparent reservoir, and terminated just superior to the third ventricle. There was no evidence of hydrocephalus; the frontal horns of the lateral ventricles were not apparent, and the right lateral ventricle had a prominent temporal horn that abutted a region of temporo-occipital hypodensity and encephalomalacia. In addition, a series of radiographs, which were obtained to assess the position and function of the ventriculoperitoneal shunt, revealed several remnants of the shunt catheter in the left thorax, as well as a large mass in the right hilum.

Dr. Adelman: Acetaminophen was administered orally, and normal saline, fentanyl, and ondansetron were administered intravenously. The following day, the patient was transferred by ambulance to the emergency department of this hospital for further treatment.

While the patient was in the ambulance, his temperature rose to 39.2°C and the headache persisted. Morphine was administered. On arrival in the emergency department, the patient reported that the severity of his headache had decreased. Several weeks earlier, he had not passed an eye examination for a driver’s license because of poor peripheral vision. He had Tourette’s syndrome and a cyst of the posterior fossa that was associated with hydrocephalus, which had been managed with ventriculoperitoneal shunting since childhood. He had undergone five shunt revisions; the most recent had been performed 24 years earlier because of shunt malfunction. He took no medications and had no known allergies. He lived with his girlfriend in New England, where he was employed in the shipbuilding industry; he enjoyed spending time outdoors and worked part-time as a nature guide. He was monogamous with his girlfriend, drank an average of four beers weekly, and did not use tobacco or illicit drugs. He had not recently traveled outside New England and had no known exposure to sick persons or tick bites. There was no family history of cancer.

On examination, the temperature was 39.2°C, the pulse 81 beats per minute, the blood pressure 121/79 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air. Left homonymous hemianopsia was present; the remainder of the general examination was unchanged. Laboratory test results are shown in Table 1.

Morphine and lorazepam were administered intravenously, and a lumbar puncture was performed with the patient in the left lateral decubitus position. The opening pressure was 24 cm of water, and the cerebrospinal fluid was clear and colorless, with a protein level of 124 mg per deciliter (reference range, 5 to 55) and a glucose level of 49 mg per deciliter (2.7 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]) and with three nucleated cells and no blood cells per microliter. Gram’s staining did not reveal any microorganisms; a specimen was sent for bacterial culture. Other laboratory test results are shown in Table 1. Blood cultures were obtained, and vancomycin, ceftriaxone, and acyclovir were administered intravenously. The patient was admitted to the hospital.

On physical examination the following morning, nontender lymphadenopathy was noted in the cervical, postauricular, supraclavicular, axillary, and inguinal regions. The spleen was not enlarged, and the temperature ranged from 36.4°C to 38.0°C. The examination was otherwise unchanged. Laboratory test results are shown in Table 1. Urinalysis revealed cloudy, amber urine, with a specific gravity of 1.017, a pH of 5.0, and 2+ urobilinogen by dipstick. Examination of a peripheral-blood smear for parasites was negative. Additional imaging studies were obtained.

Figure 1.

Imaging Studies.
Dr. Flores: Abdominal ultrasonography revealed several well-circumscribed, avascular, hypoechoic lesions abutting the pancreatic head that were thought to represent enlarged lymph nodes, as well as an exophytic, hypoechoic lesion (2 cm in diameter) at the lower pole of the left kidney. A single-view radiograph of the chest (Figure 1A) showed a fragmented ventriculoperitoneal shunt catheter on the left side. In addition, there was widening of the mediastinum and bilateral hilar nodular thickening. These findings are consistent with underlying mediastinal and bilateral hilar lymphadenopathy.

Subsequently, CT scans of the chest, abdomen, and pelvis were performed after the administration of oral and intravenous contrast material (Figure 1B through 1G). Axial images of the chest obtained with a soft-tissue window setting showed mediastinal lymphadenopathy involving several nodal stations, including the prevascular, aortopulmonary, right paratracheal, and right lower paratracheal regions. Images of the chest obtained with the lung window setting showed volume loss of the right middle lobe and atelectasis due to right hilar lymphadenopathy, which partially narrows the bronchus intermedius and partially obstructs the bronchus of the right middle lobe. A coronal image of the abdomen and pelvis obtained with a soft-tissue window setting showed extensive retroperitoneal and left inguinal lymphadenopathy, and axial images showed retroperitoneal and left external iliac lymphadenopathy and infiltrative left renal lesions.

Dr. Adelman: Vancomycin, ceftriaxone, and acyclovir were stopped. The headache persisted, and fevers continued. Morphine and acetaminophen were administered, and the patient had symptom relief.

On the third hospital day, the patient continued to feel unwell and had night sweats. Fevers to a temperature of 38.3°C continued. Laboratory test results are shown in Table 1. Manual review of the peripheral-blood smear by a hematopathologist was requested, and flow cytometry was performed.

Figure 2.

Peripheral-Blood Smear and Flow Cytometry.
Dr. Aliyah R. Sohani: Examination of the peripheral-blood smear (Figure 2A, 2B, and 2C) revealed atypical polymorphous lymphoid cells with round-to-irregular nuclei, some with nucleoli, and moderate-to-abundant cytoplasm; a few cytoplasmic granules were present in some of the cells. Plasmacytoid lymphocytes and occasional plasma cells were also present; no blasts were seen. Some neutrophils appeared to be hypogranulated, and large platelets were present. Flow cytometry of the peripheral blood revealed a differential count of 35% lymphocytes, 6% monocytes, and 54% granulocytes, as well as 3% polyclonal B cells, 27% CD3+ T cells (with no immunophenotypic abnormalities), 4% natural killer (NK) cells, 1.5% CD3+CD16+CD57+CD8+ T cells, and no myeloid or lymphoid blasts. There was a markedly inverted ratio of CD4 cells to CD8 cells of 0.08 (Figure 2D).

Dr. Adelman: Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of severe headache, fever, anorexia, fatigue, and mild nausea, along with his history of a ventriculoperitoneal shunt for hydrocephalus, suggest a possible shunt infection or malfunction. However, the CT scan did not show evidence of hydrocephalus, which would be expected with a shunt malfunction. The presence of lymphadenopathy in multiple regions and the findings on the peripheral-blood smear and flow cytometry suggest a hematologic disorder. The markedly inverted ratio of CD4 cells to CD8 cells is characteristic of HIV infection. Given the patient's symptoms, the imaging findings, and the laboratory results, the most likely diagnosis is HIV infection.\n\nDiagnosis: HIV infection.""
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        ""content"": ""The patient is a 45-year-old male with a history of Tourette's syndrome and hydrocephalus managed with a ventriculoperitoneal shunt. He presents with a severe headache, fever, anorexia, fatigue, and mild nausea. His symptoms and history suggest a possible shunt malfunction or infection. However, his lab results and imaging studies reveal lymphadenopathy in multiple regions, mediastinal and bilateral hilar lymphadenopathy, and renal lesions. These findings suggest a systemic disease, possibly lymphoma or another malignancy. However, the peripheral-blood smear and flow cytometry results do not support a diagnosis of lymphoma. The presence of atypical polymorphous lymphoid cells and a markedly inverted ratio of CD4 cells to CD8 cells suggest a viral infection, possibly HIV or another viral infection that affects the immune system. \n\nDiagnosis: HIV infection.""
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10.1056/NEJMcpc1616393,"Case 24-2017 — An 8-Month-Old Girl with Fever and an Abdominal Mass
List of authors.",,Congenital pancreatic hamartoma (multicystic adenomatoid hamartoma).,Congenital pancreatic cyst.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:             An 8-month-old girl was admitted to this hospital because of fever and an abdominal mass.

The patient had been in her usual good health until approximately 6 days before admission, when she passed a large stool surrounded by clotted blood. During the next 4 days, she had intermittent fevers with associated irritability, as well as decreased oral intake without emesis. She continued to produce 6 to 8 wet diapers per day and to pass soft, brown stools. During the day before admission, a mild cough developed. The patient was evaluated in the office of her pediatrician, and abdominal ultrasonography was scheduled for the next day. That evening, her temperature rose to 40.3°C; her parents administered ibuprofen and took her to the emergency department of another hospital.

On examination at the other hospital, the patient appeared to be in mild discomfort. The temperature was 39.4°C, the blood pressure 102/58 mm Hg, the pulse 170 beats per minute, the respiratory rate 32 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. The weight was 9.53 kg (93rd percentile). The fontanelle was open, soft, and flat. The abdomen was moderately distended, with normal bowel sounds and no apparent tenderness on palpation; the remainder of the examination was normal. Acetaminophen was administered, and the temperature decreased to 36.1°C. Analysis of a urine specimen obtained by means of catheterization revealed a pH of 5.0, a specific gravity of 1.005, a small amount of blood, and a urobilinogen level of 0.2 mg per deciliter and was otherwise normal. A blood specimen could not be obtained.

Figure 1.

Abdominal Imaging Studies Obtained at the Other Hospital.
Dr. Michael S. Gee: Abdominal radiography (Figure 1A), performed with the patient in an upright position, revealed the absence of bowel gas in the midabdomen and peripheral displacement of multiple bowel loops, findings suggestive of an abdominal mass; there was a nonobstructive bowel-gas pattern and no free intraperitoneal air or abnormal calcifications. Abdominal ultrasonography (Figure 1B) revealed a large, thick-walled complex cystic mass in the midabdomen that had internal dependent debris and multiple mural satellite cysts. The mass was located predominantly to the left of the midline, displaced the left kidney laterally, and did not have internal vascularity on Doppler imaging.

Dr. Venkatesh: The patient was transferred to this hospital 4.5 hours after her arrival at the other hospital.

The patient had been born after an uncomplicated gestation of 41 weeks’ duration. When she was 6.25 months of age (7.5 weeks before this evaluation), she was seen in the emergency department of the other hospital because she had four episodes of vomiting over a 3-hour period; she had associated grunting that was suggestive of abdominal pain but had no constipation, fever, or bleeding. On examination at that time, she was afebrile and weighed 8.15 kg (84th percentile); she had mild abdominal distention and voluntary guarding but had no palpable mass or organomegaly. Abdominal radiography revealed a nonspecific bowel-gas pattern. She was able to receive several feedings without complication, and she returned home.

The patient’s childhood immunizations were current. She took no medications and had no known allergies. She lived with her parents, a sibling, and other relatives. Her maternal grandfather had had colon cancer, and a paternal aunt had died at 20 years of age because of cancer that had been initially manifested by an abdominal cyst; there was no family history of inflammatory bowel disease.

Table 1.

Laboratory Data.
On examination, the patient was fussy but consolable. The temperature was 36.3°C, the blood pressure 105/52 mm Hg, the pulse 122 beats per minute, the respiratory rate 32 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The abdomen was soft and distended. On palpation, there was a firm fullness above the pubis but no discrete mass. The remainder of the examination was unchanged. Blood levels of glucose, calcium, phosphorus, total protein, albumin, globulin, lactate dehydrogenase, uric acid, amylase, alpha fetoprotein, and human chorionic gonadotropin were normal, as were the results of coagulation and liver-function tests; other test results are shown in Table 1. A blood culture was obtained.

Figure 2.

Abdominal Imaging Studies Obtained at This Hospital.
Dr. Gee: Computed tomography (CT) of the abdomen (Figure 2A and 2B), performed in accordance with a pediatric (low dose) protocol after the administration of intravenous and oral contrast material, revealed a complex cystic mass (measuring 14.5 cm in greatest dimension) in the midabdomen. The mass filled the left side of the abdomen and was separate from the bowel. Several loculations of the cyst abutted the pancreatic body and tail. The mass did not contain enteric contrast material, and the attenuation values of the contents of the mass were consistent with fluid.

Ultrasound-guided percutaneous drainage of the cystic mass was performed with the use of an 8-French pigtail catheter (Figure 2C). A 500-ml sample of cloudy fluid was aspirated and sent for microbiologic, hematologic, and chemical analysis. Then, iodinated contrast material was injected through the drainage catheter to identify sites of communication with the cystic mass. On fluoroscopic images obtained during the injection (Figure 2D), a curvilinear branching structure adjacent to the cyst cavity was filled with contrast material. A CT scan was obtained immediately after the injection (Figure 2E and 2F) to determine the anatomical location of this structure. During CT, only the necessary amount of radiation was used, in accordance with the Image Gently principles outlined by the Alliance for Radiation Safety in Pediatric Imaging.1 Because this was a follow-up examination targeted to a specific anatomical region, a specific pediatric (low dose) technique was used; the resultant effective dose was 1 mSv, which is equivalent to less than 1 year of background exposure. The findings on CT confirmed that the curvilinear structure filled with contrast material was the pancreatic duct (Figure 2E). In addition, contrast material was seen in the distal duodenum and proximal jejunum (Figure 2F); it had presumably passed through the ampulla.

Dr. Venkatesh: Metronidazole, gentamicin, ampicillin, and fluids were administered intravenously, and acetaminophen was administered as needed for fevers. During the next 2 days, the patient continued to have low-grade fevers.

Diagnostic procedures were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:         An 8-month-old girl was admitted to this hospital because of fever and an abdominal mass.

The patient had been in her usual good health until approximately 6 days before admission, when she passed a large stool surrounded by clotted blood. During the next 4 days, she had intermittent fevers with associated irritability, as well as decreased oral intake without emesis. She continued to produce 6 to 8 wet diapers per day and to pass soft, brown stools. During the day before admission, a mild cough developed. The patient was evaluated in the office of her pediatrician, and abdominal ultrasonography was scheduled for the next day. That evening, her temperature rose to 40.3°C; her parents administered ibuprofen and took her to the emergency department of another hospital.

On examination at the other hospital, the patient appeared to be in mild discomfort. The temperature was 39.4°C, the blood pressure 102/58 mm Hg, the pulse 170 beats per minute, the respiratory rate 32 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. The weight was 9.53 kg (93rd percentile). The fontanelle was open, soft, and flat. The abdomen was moderately distended, with normal bowel sounds and no apparent tenderness on palpation; the remainder of the examination was normal. Acetaminophen was administered, and the temperature decreased to 36.1°C. Analysis of a urine specimen obtained by means of catheterization revealed a pH of 5.0, a specific gravity of 1.005, a small amount of blood, and a urobilinogen level of 0.2 mg per deciliter and was otherwise normal. A blood specimen could not be obtained.

Figure 1.

Abdominal Imaging Studies Obtained at the Other Hospital.
Dr. Michael S. Gee: Abdominal radiography (Figure 1A), performed with the patient in an upright position, revealed the absence of bowel gas in the midabdomen and peripheral displacement of multiple bowel loops, findings suggestive of an abdominal mass; there was a nonobstructive bowel-gas pattern and no free intraperitoneal air or abnormal calcifications. Abdominal ultrasonography (Figure 1B) revealed a large, thick-walled complex cystic mass in the midabdomen that had internal dependent debris and multiple mural satellite cysts. The mass was located predominantly to the left of the midline, displaced the left kidney laterally, and did not have internal vascularity on Doppler imaging.

Dr. Venkatesh: The patient was transferred to this hospital 4.5 hours after her arrival at the other hospital.

The patient had been born after an uncomplicated gestation of 41 weeks’ duration. When she was 6.25 months of age (7.5 weeks before this evaluation), she was seen in the emergency department of the other hospital because she had four episodes of vomiting over a 3-hour period; she had associated grunting that was suggestive of abdominal pain but had no constipation, fever, or bleeding. On examination at that time, she was afebrile and weighed 8.15 kg (84th percentile); she had mild abdominal distention and voluntary guarding but had no palpable mass or organomegaly. Abdominal radiography revealed a nonspecific bowel-gas pattern. She was able to receive several feedings without complication, and she returned home.

The patient’s childhood immunizations were current. She took no medications and had no known allergies. She lived with her parents, a sibling, and other relatives. Her maternal grandfather had had colon cancer, and a paternal aunt had died at 20 years of age because of cancer that had been initially manifested by an abdominal cyst; there was no family history of inflammatory bowel disease.

Table 1.

Laboratory Data.
On examination, the patient was fussy but consolable. The temperature was 36.3°C, the blood pressure 105/52 mm Hg, the pulse 122 beats per minute, the respiratory rate 32 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The abdomen was soft and distended. On palpation, there was a firm fullness above the pubis but no discrete mass. The remainder of the examination was unchanged. Blood levels of glucose, calcium, phosphorus, total protein, albumin, globulin, lactate dehydrogenase, uric acid, amylase, alpha fetoprotein, and human chorionic gonadotropin were normal, as were the results of coagulation and liver-function tests; other test results are shown in Table 1. A blood culture was obtained.

Figure 2.

Abdominal Imaging Studies Obtained at This Hospital.
Dr. Gee: Computed tomography (CT) of the abdomen (Figure 2A and 2B), performed in accordance with a pediatric (low dose) protocol after the administration of intravenous and oral contrast material, revealed a complex cystic mass (measuring 14.5 cm in greatest dimension) in the midabdomen. The mass filled the left side of the abdomen and was separate from the bowel. Several loculations of the cyst abutted the pancreatic body and tail. The mass did not contain enteric contrast material, and the attenuation values of the contents of the mass were consistent with fluid.

Ultrasound-guided percutaneous drainage of the cystic mass was performed with the use of an 8-French pigtail catheter (Figure 2C). A 500-ml sample of cloudy fluid was aspirated and sent for microbiologic, hematologic, and chemical analysis. Then, iodinated contrast material was injected through the drainage catheter to identify sites of communication with the cystic mass. On fluoroscopic images obtained during the injection (Figure 2D), a curvilinear branching structure adjacent to the cyst cavity was filled with contrast material. A CT scan was obtained immediately after the injection (Figure 2E and 2F) to determine the anatomical location of this structure. During CT, only the necessary amount of radiation was used, in accordance with the Image Gently principles outlined by the Alliance for Radiation Safety in Pediatric Imaging.1 Because this was a follow-up examination targeted to a specific anatomical region, a specific pediatric (low dose) technique was used; the resultant effective dose was 1 mSv, which is equivalent to less than 1 year of background exposure. The findings on CT confirmed that the curvilinear structure filled with contrast material was the pancreatic duct (Figure 2E). In addition, contrast material was seen in the distal duodenum and proximal jejunum (Figure 2F); it had presumably passed through the ampulla.

Dr. Venkatesh: Metronidazole, gentamicin, ampicillin, and fluids were administered intravenously, and acetaminophen was administered as needed for fevers. During the next 2 days, the patient continued to have low-grade fevers.

Diagnostic procedures were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Pancreatic pseudocyst is the most likely diagnosis. The patient presented with fever, abdominal distension, and a history of passing a large stool surrounded by clotted blood. Imaging studies revealed a large, complex cystic mass in the midabdomen, separate from the bowel and abutting the pancreatic body and tail. The mass did not contain enteric contrast material, and the attenuation values of the contents of the mass were consistent with fluid. Furthermore, contrast material injected into the cystic mass filled a curvilinear branching structure adjacent to the cyst cavity, which was confirmed to be the pancreatic duct. This suggests that the cystic mass is connected to the pancreatic duct, which is characteristic of a pancreatic pseudocyst.""
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        ""content"": ""This is an 8-month-old girl who presents with fever and an abdominal mass. She also has a history of passing a large stool surrounded by clotted blood, intermittent fevers, irritability, and decreased oral intake. The differential diagnosis for this patient includes appendicitis, intussusception, volvulus, Meckel's diverticulum, and a pancreatic pseudocyst. Appendicitis is less likely given the absence of right lower quadrant pain and tenderness. Intussusception and volvulus are also less likely given the absence of bilious vomiting and severe abdominal pain. Meckel's diverticulum could present with painless rectal bleeding, but it would not typically cause an abdominal mass. The patient's imaging studies revealed a large, thick-walled complex cystic mass in the midabdomen with no internal vascularity, which is consistent with a pancreatic pseudocyst. Furthermore, the injection of contrast material into the cystic mass revealed a curvilinear structure filled with contrast material, which was confirmed to be the pancreatic duct. This suggests that the cystic mass is connected to the pancreatic duct, which is characteristic of a pancreatic pseudocyst. \n\nDiagnosis: Pancreatic pseudocyst.""
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10.1056/NEJMcpc1703512,"Case 23-2017 — A 9-Day-Old Girl with Vomiting, Acidosis, and Azotemia",,Food protein–induced enterocolitis syndrome.,Food protein–induced enterocolitis syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                A 9-day-old girl was admitted to this hospital because of nonbilious vomiting, acidosis, and azotemia.

The patient had been born at another hospital by induced vaginal delivery after 41 weeks 3 days of gestation. The pregnancy had been complicated by maternal obesity. The patient was placed with an adoptive family immediately after birth. Her birth mother had received prenatal care, and screening tests for gonorrhea, chlamydia, syphilis, human immunodeficiency virus, and hepatitis B virus had been negative; a screening test for immunity to rubella virus was positive, as was a screening test for group B streptococcal colonization. Spontaneous rupture of membranes, which occurred 2 hours before birth, revealed meconium-stained amniotic fluid, and five doses of penicillin were administered before delivery. The 1-minute and 5-minute Apgar scores were 8 and 9, respectively.

At birth, the weight was 3.9 kg (87th percentile), the length 51.5 cm (80th percentile), and the head circumference 36.5 cm (85th percentile); the vital signs and physical examination were normal. A diet of organic cow’s milk–based infant formula with a probiotic was begun shortly after birth; the patient drank the formula avidly, and urine and stool output were normal for her age. The results of newborn blood-spot screening tests (i.e., a panel of tests for multiple congenital diseases, primarily inborn errors of metabolism) and screening tests for hearing ability and critical congenital heart disease were normal, and the patient received intramuscular vitamin K, erythromycin ophthalmic ointment, and a hepatitis B immunization before discharge.

Five days before this admission, at a routine pediatric examination, the patient’s adoptive parents reported that she had been drinking 60 ml of formula every 3 to 4 hours, with some “spit ups,” and that she produced four yellow-brown stools each day. She appeared well, with mild jaundice, and was scheduled to return 10 days later for another routine appointment.

One day before this admission, nonprojectile, nonbloody, nonbilious vomiting occurred after each feed. The baby was fussier and less active than usual and drank only 30 to 45 ml of formula per feed before falling asleep, as compared with the 90 to 105 ml per feed she had had the previous day. Her father called the pediatrician during the evening and was advised to take the baby to the emergency department at another hospital.

Table 1.

Laboratory Data.
On presentation to the other hospital, the patient was alert and responded appropriately to physical examination. The temperature was 37.8°C, the pulse 120 beats per minute, the blood pressure 85/59 mm Hg, the respiratory rate 36 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The weight was 3.5 kg. The anterior fontanelle was sunken; the remainder of the examination was normal. A lumbar puncture was performed. Samples of blood, urine, stool, and cerebrospinal fluid were obtained for culture. Tests for respiratory syncytial virus and rotavirus were negative. Blood levels of total protein, albumin, total bilirubin, direct bilirubin, and alkaline phosphatase were normal; other laboratory test results are shown in Table 1. Urinalysis revealed orange urine, with a pH of 5.0, a specific gravity higher than 1.030, 3+ protein, and 2+ bilirubin. A chest radiograph was normal. Multiple attempts to place an intravenous catheter were unsuccessful; ampicillin and ceftriaxone were administered intramuscularly, and an enteral electrolyte solution was administered through a nasogastric tube and did not cause vomiting. Early during the following day, the patient was transferred to the pediatric intensive care unit (ICU) at this hospital for further evaluation and treatment.

The patient had lived with her adoptive family in an urban area of New England since birth. Her biologic half-brother had autism and eczema and had undergone placement of tympanostomy tubes. The patient had no known exposure to sick persons.

On admission to this hospital, the results of physical examination were unchanged. A peripheral intravenous catheter was inserted, and a bolus of normal saline was administered, followed by a continuous infusion of 10% dextrose in water with 0.225% normal saline. The point-of-care blood glucose level was 84 mg per deciliter (4.7 mmol per liter; reference range, 60 to 100 mg per deciliter [3.3 to 5.6 mmol per liter]). Ampicillin and cefepime were administered intravenously. Tests for respiratory syncytial virus, metapneumovirus, adenovirus, and parainfluenza viruses were negative; other laboratory test results are shown in Table 1. The patient was fed a cow’s milk–based formula, and vomiting recurred. Enteral feeding was stopped, the administration of intravenous fluid was continued, and vomiting ceased.

The next day, the physical examination was normal. The results of an acylcarnitine profile analysis were normal, as were the results of blood amino acid analysis, with the exception of an alanine level of 582 nmol per milliliter (reference range, 139 to 474). Other laboratory test results are shown in Table 1. Urinalysis revealed clear, yellow urine, with a pH of 6.0, a specific gravity of 1.008, and 1+ glucose. An electrocardiogram was normal.

Dr. Rene Balza: An upper gastrointestinal series showed severe spontaneous gastroesophageal reflux; there was no evidence of intestinal malrotation. Ultrasonography of the kidneys and bladder revealed mild pyelectasis in the left kidney and was otherwise normal; limited abdominal ultrasonography revealed no evidence of pyloric stenosis.

Dr. Tuttle: The cultures of blood, urine, stool, and cerebrospinal fluid that had been performed at the other hospital remained negative, and ampicillin and cefepime were discontinued. Oral administration of an electrolyte solution was begun and did not cause vomiting.

On the third hospital day, the patient was transferred to the pediatric unit. Her home diet of an organic cow’s milk–based formula with a probiotic was resumed. Overnight, she vomited once, approximately 2 hours after a feed. Vomiting after feeds continued during the next day. A diet of an oral electrolyte solution was resumed, and vomiting ceased. On the fifth hospital day, oral administration of an amino acid–based formula was begun and did not cause vomiting. The results of repeat newborn blood-spot screening tests were reported as normal; other laboratory test results are shown in Table 1. Over the next 2 days, the patient continued to receive the amino acid–based formula without vomiting; the administration of intravenous fluid was stopped. Laboratory test results obtained on the sixth and seventh hospital days are shown in Table 1. The patient was discharged home on the seventh hospital day, at which time the weight was 3.4 kg.

Three days after discharge, the patient was seen for follow-up by her pediatrician. Her parents reported that she had had five episodes of spitting up during the previous 24 hours, that she had appeared tired and pale, and that her oral intake had decreased, such that she had consumed only 5 to 25 ml of the amino acid–based formula per feed that day. She was also producing frequent loose, small-volume, greenish stools (10 in a 24-hour period); during the bowel movements, borborygmi were audible and the patient arched her back.

On examination, the patient appeared pale and sleepy but aroused during the examination. The temperature was 37.3°C, the pulse 132 beats per minute, and the weight 3.0 kg. The anterior fontanelle was sunken, the lips were dry, skin turgor was decreased, and the capillary refill time was between 2 and 3 seconds. The patient vomited once in the clinic. The point-of-care blood glucose level was 98 mg per deciliter (5.4 mmol per liter). The patient was fed an oral electrolyte solution and then was referred to the emergency department of this hospital.

On arrival at the emergency department, the patient was lethargic and her skin appeared ashen; she cried weakly and without tears. The temperature was 37.8°C, the pulse 166 beats per minute, the blood pressure 73/50 mm Hg, the respiratory rate 58 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The remainder of the examination was unchanged. Samples of blood and stool were obtained for culture. Blood levels of total protein, albumin, globulin, total bilirubin, direct bilirubin, and alkaline phosphatase were normal; other laboratory test results are shown in Table 1. Urinalysis revealed clear, yellow urine, with a pH of 6.0, a specific gravity of 1.030, and 2+ protein by dipstick; on microscopic examination, there were 0 to 2 red cells per high-power field, 5 to 10 white cells per high-power field, and 5 to 10 hyaline casts per low-power field. The patient was admitted to the pediatric ICU.

A bolus of normal saline was administered intravenously, followed by a continuous infusion of 5% dextrose with sodium bicarbonate and potassium chloride. The patient received an oral electrolyte solution without vomiting.

Figure 1.

Imaging Studies.
Dr. Balza: The next day, a central venous catheter was placed; abdominal radiography, which was performed to assess its position, revealed an abnormal bowel-gas pattern with narrowing of the lumen and separation of the bowel loops, findings suggestive of bowel-wall thickening or ascites (Figure 1A). Abdominal ultrasonography revealed fluid-filled bowel loops with thickened walls (measuring up to 3 mm in thickness), as well as a small amount of associated free intraperitoneal fluid in the right half of the abdomen (Figure 1B and 1C).

Dr. Tuttle: Stools continued to be loose and were guaiac-positive. Enteral feeds were discontinued, and the administration of total parenteral nutrition was initiated. Pantoprazole, ampicillin, cefepime, and metronidazole were administered intravenously.

Over the next 2 weeks, additional diagnostic studies were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                           A 9-day-old girl was admitted to this hospital because of nonbilious vomiting, acidosis, and azotemia.

The patient had been born at another hospital by induced vaginal delivery after 41 weeks 3 days of gestation. The pregnancy had been complicated by maternal obesity. The patient was placed with an adoptive family immediately after birth. Her birth mother had received prenatal care, and screening tests for gonorrhea, chlamydia, syphilis, human immunodeficiency virus, and hepatitis B virus had been negative; a screening test for immunity to rubella virus was positive, as was a screening test for group B streptococcal colonization. Spontaneous rupture of membranes, which occurred 2 hours before birth, revealed meconium-stained amniotic fluid, and five doses of penicillin were administered before delivery. The 1-minute and 5-minute Apgar scores were 8 and 9, respectively.

At birth, the weight was 3.9 kg (87th percentile), the length 51.5 cm (80th percentile), and the head circumference 36.5 cm (85th percentile); the vital signs and physical examination were normal. A diet of organic cow’s milk–based infant formula with a probiotic was begun shortly after birth; the patient drank the formula avidly, and urine and stool output were normal for her age. The results of newborn blood-spot screening tests (i.e., a panel of tests for multiple congenital diseases, primarily inborn errors of metabolism) and screening tests for hearing ability and critical congenital heart disease were normal, and the patient received intramuscular vitamin K, erythromycin ophthalmic ointment, and a hepatitis B immunization before discharge.

Five days before this admission, at a routine pediatric examination, the patient’s adoptive parents reported that she had been drinking 60 ml of formula every 3 to 4 hours, with some “spit ups,” and that she produced four yellow-brown stools each day. She appeared well, with mild jaundice, and was scheduled to return 10 days later for another routine appointment.

One day before this admission, nonprojectile, nonbloody, nonbilious vomiting occurred after each feed. The baby was fussier and less active than usual and drank only 30 to 45 ml of formula per feed before falling asleep, as compared with the 90 to 105 ml per feed she had had the previous day. Her father called the pediatrician during the evening and was advised to take the baby to the emergency department at another hospital.

Table 1.

Laboratory Data.
On presentation to the other hospital, the patient was alert and responded appropriately to physical examination. The temperature was 37.8°C, the pulse 120 beats per minute, the blood pressure 85/59 mm Hg, the respiratory rate 36 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The weight was 3.5 kg. The anterior fontanelle was sunken; the remainder of the examination was normal. A lumbar puncture was performed. Samples of blood, urine, stool, and cerebrospinal fluid were obtained for culture. Tests for respiratory syncytial virus and rotavirus were negative. Blood levels of total protein, albumin, total bilirubin, direct bilirubin, and alkaline phosphatase were normal; other laboratory test results are shown in Table 1. Urinalysis revealed orange urine, with a pH of 5.0, a specific gravity higher than 1.030, 3+ protein, and 2+ bilirubin. A chest radiograph was normal. Multiple attempts to place an intravenous catheter were unsuccessful; ampicillin and ceftriaxone were administered intramuscularly, and an enteral electrolyte solution was administered through a nasogastric tube and did not cause vomiting. Early during the following day, the patient was transferred to the pediatric intensive care unit (ICU) at this hospital for further evaluation and treatment.

The patient had lived with her adoptive family in an urban area of New England since birth. Her biologic half-brother had autism and eczema and had undergone placement of tympanostomy tubes. The patient had no known exposure to sick persons.

On admission to this hospital, the results of physical examination were unchanged. A peripheral intravenous catheter was inserted, and a bolus of normal saline was administered, followed by a continuous infusion of 10% dextrose in water with 0.225% normal saline. The point-of-care blood glucose level was 84 mg per deciliter (4.7 mmol per liter; reference range, 60 to 100 mg per deciliter [3.3 to 5.6 mmol per liter]). Ampicillin and cefepime were administered intravenously. Tests for respiratory syncytial virus, metapneumovirus, adenovirus, and parainfluenza viruses were negative; other laboratory test results are shown in Table 1. The patient was fed a cow’s milk–based formula, and vomiting recurred. Enteral feeding was stopped, the administration of intravenous fluid was continued, and vomiting ceased.

The next day, the physical examination was normal. The results of an acylcarnitine profile analysis were normal, as were the results of blood amino acid analysis, with the exception of an alanine level of 582 nmol per milliliter (reference range, 139 to 474). Other laboratory test results are shown in Table 1. Urinalysis revealed clear, yellow urine, with a pH of 6.0, a specific gravity of 1.008, and 1+ glucose. An electrocardiogram was normal.

Dr. Rene Balza: An upper gastrointestinal series showed severe spontaneous gastroesophageal reflux; there was no evidence of intestinal malrotation. Ultrasonography of the kidneys and bladder revealed mild pyelectasis in the left kidney and was otherwise normal; limited abdominal ultrasonography revealed no evidence of pyloric stenosis.

Dr. Tuttle: The cultures of blood, urine, stool, and cerebrospinal fluid that had been performed at the other hospital remained negative, and ampicillin and cefepime were discontinued. Oral administration of an electrolyte solution was begun and did not cause vomiting.

On the third hospital day, the patient was transferred to the pediatric unit. Her home diet of an organic cow’s milk–based formula with a probiotic was resumed. Overnight, she vomited once, approximately 2 hours after a feed. Vomiting after feeds continued during the next day. A diet of an oral electrolyte solution was resumed, and vomiting ceased. On the fifth hospital day, oral administration of an amino acid–based formula was begun and did not cause vomiting. The results of repeat newborn blood-spot screening tests were reported as normal; other laboratory test results are shown in Table 1. Over the next 2 days, the patient continued to receive the amino acid–based formula without vomiting; the administration of intravenous fluid was stopped. Laboratory test results obtained on the sixth and seventh hospital days are shown in Table 1. The patient was discharged home on the seventh hospital day, at which time the weight was 3.4 kg.

Three days after discharge, the patient was seen for follow-up by her pediatrician. Her parents reported that she had had five episodes of spitting up during the previous 24 hours, that she had appeared tired and pale, and that her oral intake had decreased, such that she had consumed only 5 to 25 ml of the amino acid–based formula per feed that day. She was also producing frequent loose, small-volume, greenish stools (10 in a 24-hour period); during the bowel movements, borborygmi were audible and the patient arched her back.

On examination, the patient appeared pale and sleepy but aroused during the examination. The temperature was 37.3°C, the pulse 132 beats per minute, and the weight 3.0 kg. The anterior fontanelle was sunken, the lips were dry, skin turgor was decreased, and the capillary refill time was between 2 and 3 seconds. The patient vomited once in the clinic. The point-of-care blood glucose level was 98 mg per deciliter (5.4 mmol per liter). The patient was fed an oral electrolyte solution and then was referred to the emergency department of this hospital.

On arrival at the emergency department, the patient was lethargic and her skin appeared ashen; she cried weakly and without tears. The temperature was 37.8°C, the pulse 166 beats per minute, the blood pressure 73/50 mm Hg, the respiratory rate 58 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The remainder of the examination was unchanged. Samples of blood and stool were obtained for culture. Blood levels of total protein, albumin, globulin, total bilirubin, direct bilirubin, and alkaline phosphatase were normal; other laboratory test results are shown in Table 1. Urinalysis revealed clear, yellow urine, with a pH of 6.0, a specific gravity of 1.030, and 2+ protein by dipstick; on microscopic examination, there were 0 to 2 red cells per high-power field, 5 to 10 white cells per high-power field, and 5 to 10 hyaline casts per low-power field. The patient was admitted to the pediatric ICU.

A bolus of normal saline was administered intravenously, followed by a continuous infusion of 5% dextrose with sodium bicarbonate and potassium chloride. The patient received an oral electrolyte solution without vomiting.

Figure 1.

Imaging Studies.
Dr. Balza: The next day, a central venous catheter was placed; abdominal radiography, which was performed to assess its position, revealed an abnormal bowel-gas pattern with narrowing of the lumen and separation of the bowel loops, findings suggestive of bowel-wall thickening or ascites (Figure 1A). Abdominal ultrasonography revealed fluid-filled bowel loops with thickened walls (measuring up to 3 mm in thickness), as well as a small amount of associated free intraperitoneal fluid in the right half of the abdomen (Figure 1B and 1C).

Dr. Tuttle: Stools continued to be loose and were guaiac-positive. Enteral feeds were discontinued, and the administration of total parenteral nutrition was initiated. Pantoprazole, ampicillin, cefepime, and metronidazole were administered intravenously.

Over the next 2 weeks, additional diagnostic studies were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Congenital chloride diarrhea. The patient's symptoms of nonbilious vomiting, acidosis, and azotemia, along with the presence of hyponatremia and hypochloremia in the blood tests, suggest a loss of electrolytes. The patient's stools were also described as loose and frequent, which is consistent with diarrhea. The patient's symptoms improved when she was switched to an amino acid-based formula, suggesting that her symptoms were related to her diet. The patient's symptoms worsened again when she was switched back to her regular diet, further suggesting a dietary cause. The patient's symptoms and the improvement with an amino acid-based formula suggest a disorder of electrolyte absorption in the intestines. Congenital chloride diarrhea is a rare genetic disorder characterized by the inability to absorb chloride in the intestines, leading to large, watery stools, electrolyte imbalances, and dehydration.""
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        ""content"": ""Congenital chloride diarrhea. The patient's symptoms of nonbilious vomiting, acidosis, and azotemia, along with the laboratory findings of hyponatremia, hypokalemia, and hypochloremia, suggest a disorder of electrolyte balance. The patient's history of frequent loose, greenish stools and the finding of high chloride concentration in the stool point to a diagnosis of congenital chloride diarrhea. This is a rare autosomal recessive disorder characterized by the defective transport of chloride and sodium ions in the intestines, leading to large-volume diarrhea, electrolyte imbalances, and metabolic alkalosis.""
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        ""content"": ""This is a 9-day-old girl who presents with nonbilious vomiting, acidosis, and azotemia. The differential diagnosis for this patient includes pyloric stenosis, gastroenteritis, metabolic disorders, and congenital renal disorders. Pyloric stenosis is less likely given the absence of a palpable \""olive\"" mass in the epigastric region and the ultrasound did not show any evidence of pyloric stenosis. Gastroenteritis is also less likely given the negative tests for common viral causes and the absence of diarrhea. Metabolic disorders such as inborn errors of metabolism were ruled out by the normal newborn screening tests. The patient's azotemia and acidosis suggest a renal disorder. The patient's urinalysis showed proteinuria and hyaline casts, which are indicative of renal tubular damage. The patient's symptoms improved with the administration of an amino acid-based formula, suggesting a disorder related to protein metabolism. The patient's presentation is consistent with a congenital renal tubular disorder, specifically, renal tubular acidosis (RTA). RTA is characterized by normal anion gap metabolic acidosis, which was seen in this patient. The patient's failure to thrive, vomiting, and electrolyte imbalances are also consistent with RTA.\n\nDiagnosis: Renal tubular acidosis.""
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10.1056/NEJMcpc1616399,"Case 22-2017 — A 21-Year-Old Woman with Fever, Headache, and Myalgias
List of authors.",,Probable acute leptospirosis.,Leptospirosis,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                      A 21-year-old woman was admitted to this hospital during the winter because of fever, headache, and myalgias.

The patient had been well until 4 days before this admission, when fever, chills, fatigue, malaise, retro-orbital headache, and photophobia developed. On presentation to a clinic affiliated with the university where she was a student, she reported that, 6 days earlier, she had returned from a trip to Indonesia. A blood-smear examination for malaria was negative, and the patient was advised to take acetaminophen and ibuprofen. Over the next 2 days, her symptoms worsened, and abdominal pain in the left lower quadrant and arthralgias affecting the knees developed. On the third day of illness, she presented to the emergency department of another hospital for evaluation.

Table 1.

Laboratory Data.
On examination at the other hospital, the temperature was 41.0°C. The blood lactic acid level and results of liver-function tests were normal; other laboratory test results are shown in Table 1. Tests for heterophile antibodies, influenza, and Clostridium difficile were negative. Blood and urine specimens were obtained for culture, and a lumbar puncture was performed; on cerebrospinal fluid analysis, the white-cell and red-cell counts and protein and glucose levels were normal.

Dr. Rydhwana Hossain: Chest radiography revealed no evidence of focal consolidation, pulmonary edema, or hilar adenopathy. Abdominal radiography revealed multiple air-filled loops of small bowel but no evidence of abnormal bowel dilatation, obstruction, or free air. Four hours later, computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed the presence of a few subcentimeter mesenteric lymph nodes in the right lower quadrant. There was no bowel-wall thickening, obstruction, ascites, or hepatosplenomegaly. The kidneys were heterogeneous in appearance.

Dr. Mgbojikwe: Acetaminophen was administered, and the patient was admitted to the hospital. High temperatures persisted; cooling blankets were applied, and more than 7 liters of fluid were administered intravenously. On the second hospital day, intravenous doxycycline and ceftriaxone were administered. Three blood-smear examinations for malaria, a stool culture for enteric pathogens, and a stool examination for ova and parasites were negative; other laboratory test results are shown in Table 1. By the third hospital day, cough and mild chest pain had developed, and hypoxemia was reportedly present; supplemental oxygen was administered, initially through a nasal cannula at a flow rate of 4 liters per minute and then through a nonrebreather face mask at a flow rate of 15 liters per minute.

Figure 1.

Chest Radiographs.
Dr. Hossain: Repeat chest radiography revealed diffuse, hazy opacities, predominantly in the lower lobes, with new opacification of the left hemidiaphragm (Figure 1A).

Dr. Mgbojikwe: Headache and photophobia persisted. A CT scan of the head was normal. Doxycycline was continued, ceftriaxone was discontinued, and vancomycin and piperacillin–tazobactam were administered intravenously. The patient was transferred to the intensive care unit (ICU) at the other hospital.

In the ICU, the blood levels of lactic acid, amylase, lipase, and creatine kinase were normal, and tests for rheumatoid factor, antinuclear antibodies, and antineutrophil cytoplasmic antibodies were negative; other laboratory test results are shown in Table 1. An electrocardiogram and a transthoracic echocardiogram were normal. Furosemide was administered intravenously, and the patient had 3 liters of urine output. Therapy with oral oseltamivir and a continuous intravenous infusion of sodium bicarbonate was begun, and the patient was transferred by helicopter to the medical ICU at this hospital.

On admission to this hospital, the patient reported that fevers had occurred without periodicity and that photophobia, headache, and diffuse myalgias persisted. She had a history of anxiety and exercise-induced asthma and a remote history of tonsillectomy and adenoidectomy. Her only medication was citalopram, and she had no known allergies. She was a college student and lived with roommates in a rural area of New England. Twenty-seven days before the onset of illness, she had returned from a 10-day trip to the U.S. Virgin Islands. Six days before the onset of illness, she had returned from a 16-day ecology tour in rural Indonesia; she had traveled through the United Arab Emirates in transit to Indonesia, and the passenger seated next to her on the flight from the United Arab Emirates to Indonesia coughed intermittently during the trip. The patient did not receive any vaccinations before the trip and did not take malaria prophylaxis. While she was in Indonesia, she used mosquito netting during sleep but received multiple mosquito bites. She drank boiled water and pasteurized milk and ate rice and beans, thoroughly cooked meat, and fruit that had been washed but not peeled. She visited jungles and plantations and had contact with elephants, a bovine calf, and a juvenile macaque. She also observed but did not have contact with cats, dogs, bats, chickens, and cattle. She swam in jungle streams, ponds, and a waterfall pool. She reported that at the midpoint of the trip, a mild, nonpainful, nonpruritic rash developed; the rash first appeared on the wrists, spread centripetally and became diffuse, and then resolved. She was monogamous with her boyfriend, and they used condoms inconsistently. She did not smoke tobacco, but she smoked marijuana occasionally and drank alcohol rarely.

Figure 2.

Clinical Photograph.
On examination, the patient was irritable and appeared tired. The temperature was 37.2°C, the pulse 80 beats per minute, the blood pressure 112/57 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while she was receiving supplemental oxygen through a high-flow nasal cannula (at a flow rate of 50 liters per minute, with a fraction of inspired oxygen of 0.5). She had a few petechiae on the palate, palpebral conjunctival injection, and mild neck stiffness. On auscultation of the chest, there were rales over both lung bases. There was mild, diffuse abdominal tenderness that was worst in the left lower quadrant, as well as a very faint blanching, macular rash on the thighs, arms, and lower abdomen (Figure 2). Application of a tourniquet to an arm for 5 minutes did not precipitate the development of petechiae. The remainder of the physical examination was normal. The red-cell indexes, anion gap, and blood levels of glucose, lactic acid, lactate dehydrogenase, and lipase were normal, as were the results of liver-function tests. Other laboratory test results are shown in Table 1. A rapid test for malaria antigen, a pregnancy test, and a polymerase-chain-reaction (PCR) test for influenza were negative. Urinalysis showed slightly cloudy yellow urine, with 1+ ketones, 1+ occult blood, a specific gravity of 1.012, and a pH of 5.0; on microscopic examination, amorphous crystals and mucin were present, and there were 0 to 2 red cells per high-power field, no white cells per high-power field, and 0 to 2 hyaline casts per low-power field.

Dr. Hossain: Chest radiography revealed rapidly progressing confluent perihilar opacities that were more prominent on the left side than on the right side, as well as a new small pleural effusion on the left side (Figure 1B). The left hemidiaphragm was completely obscured, possibly because of consolidation or atelectasis.

Dr. Mgbojikwe: A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                            A 21-year-old woman was admitted to this hospital during the winter because of fever, headache, and myalgias.

The patient had been well until 4 days before this admission, when fever, chills, fatigue, malaise, retro-orbital headache, and photophobia developed. On presentation to a clinic affiliated with the university where she was a student, she reported that, 6 days earlier, she had returned from a trip to Indonesia. A blood-smear examination for malaria was negative, and the patient was advised to take acetaminophen and ibuprofen. Over the next 2 days, her symptoms worsened, and abdominal pain in the left lower quadrant and arthralgias affecting the knees developed. On the third day of illness, she presented to the emergency department of another hospital for evaluation.

Table 1.

Laboratory Data.
On examination at the other hospital, the temperature was 41.0°C. The blood lactic acid level and results of liver-function tests were normal; other laboratory test results are shown in Table 1. Tests for heterophile antibodies, influenza, and Clostridium difficile were negative. Blood and urine specimens were obtained for culture, and a lumbar puncture was performed; on cerebrospinal fluid analysis, the white-cell and red-cell counts and protein and glucose levels were normal.

Dr. Rydhwana Hossain: Chest radiography revealed no evidence of focal consolidation, pulmonary edema, or hilar adenopathy. Abdominal radiography revealed multiple air-filled loops of small bowel but no evidence of abnormal bowel dilatation, obstruction, or free air. Four hours later, computed tomography (CT) of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed the presence of a few subcentimeter mesenteric lymph nodes in the right lower quadrant. There was no bowel-wall thickening, obstruction, ascites, or hepatosplenomegaly. The kidneys were heterogeneous in appearance.

Dr. Mgbojikwe: Acetaminophen was administered, and the patient was admitted to the hospital. High temperatures persisted; cooling blankets were applied, and more than 7 liters of fluid were administered intravenously. On the second hospital day, intravenous doxycycline and ceftriaxone were administered. Three blood-smear examinations for malaria, a stool culture for enteric pathogens, and a stool examination for ova and parasites were negative; other laboratory test results are shown in Table 1. By the third hospital day, cough and mild chest pain had developed, and hypoxemia was reportedly present; supplemental oxygen was administered, initially through a nasal cannula at a flow rate of 4 liters per minute and then through a nonrebreather face mask at a flow rate of 15 liters per minute.

Figure 1.

Chest Radiographs.
Dr. Hossain: Repeat chest radiography revealed diffuse, hazy opacities, predominantly in the lower lobes, with new opacification of the left hemidiaphragm (Figure 1A).

Dr. Mgbojikwe: Headache and photophobia persisted. A CT scan of the head was normal. Doxycycline was continued, ceftriaxone was discontinued, and vancomycin and piperacillin–tazobactam were administered intravenously. The patient was transferred to the intensive care unit (ICU) at the other hospital.

In the ICU, the blood levels of lactic acid, amylase, lipase, and creatine kinase were normal, and tests for rheumatoid factor, antinuclear antibodies, and antineutrophil cytoplasmic antibodies were negative; other laboratory test results are shown in Table 1. An electrocardiogram and a transthoracic echocardiogram were normal. Furosemide was administered intravenously, and the patient had 3 liters of urine output. Therapy with oral oseltamivir and a continuous intravenous infusion of sodium bicarbonate was begun, and the patient was transferred by helicopter to the medical ICU at this hospital.

On admission to this hospital, the patient reported that fevers had occurred without periodicity and that photophobia, headache, and diffuse myalgias persisted. She had a history of anxiety and exercise-induced asthma and a remote history of tonsillectomy and adenoidectomy. Her only medication was citalopram, and she had no known allergies. She was a college student and lived with roommates in a rural area of New England. Twenty-seven days before the onset of illness, she had returned from a 10-day trip to the U.S. Virgin Islands. Six days before the onset of illness, she had returned from a 16-day ecology tour in rural Indonesia; she had traveled through the United Arab Emirates in transit to Indonesia, and the passenger seated next to her on the flight from the United Arab Emirates to Indonesia coughed intermittently during the trip. The patient did not receive any vaccinations before the trip and did not take malaria prophylaxis. While she was in Indonesia, she used mosquito netting during sleep but received multiple mosquito bites. She drank boiled water and pasteurized milk and ate rice and beans, thoroughly cooked meat, and fruit that had been washed but not peeled. She visited jungles and plantations and had contact with elephants, a bovine calf, and a juvenile macaque. She also observed but did not have contact with cats, dogs, bats, chickens, and cattle. She swam in jungle streams, ponds, and a waterfall pool. She reported that at the midpoint of the trip, a mild, nonpainful, nonpruritic rash developed; the rash first appeared on the wrists, spread centripetally and became diffuse, and then resolved. She was monogamous with her boyfriend, and they used condoms inconsistently. She did not smoke tobacco, but she smoked marijuana occasionally and drank alcohol rarely.

Figure 2.

Clinical Photograph.
On examination, the patient was irritable and appeared tired. The temperature was 37.2°C, the pulse 80 beats per minute, the blood pressure 112/57 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while she was receiving supplemental oxygen through a high-flow nasal cannula (at a flow rate of 50 liters per minute, with a fraction of inspired oxygen of 0.5). She had a few petechiae on the palate, palpebral conjunctival injection, and mild neck stiffness. On auscultation of the chest, there were rales over both lung bases. There was mild, diffuse abdominal tenderness that was worst in the left lower quadrant, as well as a very faint blanching, macular rash on the thighs, arms, and lower abdomen (Figure 2). Application of a tourniquet to an arm for 5 minutes did not precipitate the development of petechiae. The remainder of the physical examination was normal. The red-cell indexes, anion gap, and blood levels of glucose, lactic acid, lactate dehydrogenase, and lipase were normal, as were the results of liver-function tests. Other laboratory test results are shown in Table 1. A rapid test for malaria antigen, a pregnancy test, and a polymerase-chain-reaction (PCR) test for influenza were negative. Urinalysis showed slightly cloudy yellow urine, with 1+ ketones, 1+ occult blood, a specific gravity of 1.012, and a pH of 5.0; on microscopic examination, amorphous crystals and mucin were present, and there were 0 to 2 red cells per high-power field, no white cells per high-power field, and 0 to 2 hyaline casts per low-power field.

Dr. Hossain: Chest radiography revealed rapidly progressing confluent perihilar opacities that were more prominent on the left side than on the right side, as well as a new small pleural effusion on the left side (Figure 1B). The left hemidiaphragm was completely obscured, possibly because of consolidation or atelectasis.

Dr. Mgbojikwe: A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Dengue Fever. The patient's symptoms of fever, headache, myalgias, and retro-orbital pain, along with her recent travel history to Indonesia, suggest a tropical infectious disease. The presence of a rash, petechiae, and negative malaria tests further support a diagnosis of dengue fever. Dengue fever is a mosquito-borne viral illness common in tropical and subtropical regions. The patient's report of multiple mosquito bites during her trip to Indonesia also supports this diagnosis.""
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        ""content"": ""The patient's symptoms of fever, headache, myalgias, and retro-orbital pain, along with her recent travel history to Indonesia, suggest a tropical infectious disease. The negative malaria tests and the presence of a rash that spread centripetally and then resolved suggest dengue fever, which is endemic in Indonesia. Dengue fever is a mosquito-borne viral illness that can cause high fever, severe headache, pain behind the eyes, joint and muscle pain, rash, and mild bleeding. The patient's symptoms and her exposure to mosquitoes during her trip to Indonesia support this diagnosis.\n\nDengue Fever.""
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        ""content"": ""The patient is a 21-year-old woman presenting with fever, headache, myalgias, and a history of recent travel to Indonesia. The differential diagnosis includes malaria, dengue fever, typhoid fever, leptospirosis, and rickettsial diseases. Malaria is less likely given the negative blood smear and antigen test. Dengue fever is a possibility given the patient's symptoms and travel history, but the absence of a rash and the presence of abdominal pain make it less likely. Typhoid fever could present with similar symptoms, but the patient's normal white blood cell count and the absence of diarrhea make it less likely. Leptospirosis could also present with similar symptoms and is associated with exposure to contaminated water, which fits with the patient's history of swimming in jungle streams, ponds, and a waterfall pool. However, the patient's normal white blood cell count and the absence of jaundice make it less likely. Rickettsial diseases, such as scrub typhus, could present with similar symptoms and are associated with exposure to mites, which fits with the patient's history of jungle visits. The presence of a rash, which is common in rickettsial diseases, also supports this diagnosis. \n\nDiagnosis: Rickettsial disease, likely scrub typhus.""
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10.1056/NEJMcpc1616401,"Case 20-2017 — A 48-Year-Old Man with Weight Loss, Confusion, Skin Lesions, and Pancytopenia",,"Advanced acquired immunodeficiency syndrome (AIDS) complicated by human immunodeficiency virus type 1 (HIV-1) encephalopathy.

Basal-cell carcinoma.

Kaposi’s sarcoma.",Advanced human immunodeficiency virus type 1 (HIV-1) infection complicated by Kaposi’s sarcoma and HIV-1 encephalopathy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:               A 48-year-old man was seen in the emergency department of this hospital because of confusion.

The week before this presentation, the patient, who was a lawyer, had traveled alone to Mexico for vacation. His family reported that he seemed to be in his usual health before the trip but that, when they spoke with him by telephone while he was in Mexico (4 days before this presentation), he seemed euphoric and easily distracted, which were notable changes from baseline. They were then unable to reach him by telephone for 72 hours and became increasingly concerned about his well-being. Ultimately, he was reached by telephone; he was agitated and refused to board his scheduled return flight. The patient’s mother traveled from the United States to Mexico, where she found the patient to be confused and unkempt and to have lost his wallet and passport; he was drinking alcohol and insisting that he needed to travel immediately to New York City to work on an important legal case. His mother escorted him on a flight back to the United States and brought him to the emergency department of this hospital for evaluation.

In the emergency department, family members reported that the patient had begun having unexplained weight loss approximately 1 year earlier. The patient reported a history of multiple nonmelanoma skin cancers that had been treated with cryotherapy; he had also adopted a diet low in added sugar, which he believed had led to improvement in the appearance of the skin lesions. He had undergone sigmoidoscopy 12 years earlier to remove a foreign body from the sigmoid colon. He took melatonin and was allergic to penicillin. He was single, lived alone in an urban area of New England, and frequently traveled to Mexico; he had sex with men and used condoms intermittently. He drank alcohol in moderation and did not smoke or use illicit drugs. There was no family history of dementia, stroke, seizure disorder, cancer, depression, bipolar disorder, or schizophrenia.

On examination, the patient appeared thin and agitated. The temperature was 35.8°C, the pulse 71 beats per minute, the blood pressure 120/62 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. He was alert and oriented to which city he was in and to the year but not the month. When he was asked why he was in the emergency department, his response revealed anosognosia and confabulation. He had nonfluent aphasia and perseverated when speaking, but he had no dysarthria and was able to repeat words, name objects and the current president, and pantomime brushing his hair and teeth. He performed simple calculations accurately but was unable to perform two-part commands; he was slow when he spelled “table” and “world” backward and when he counted down from 100 in increments of 7. He could not provide abstract explanations for proverbs.

Examination of the function of cranial nerves II through XII revealed left-eye ptosis, a finding that was also visible on the patient’s driver’s license photograph, which had been taken in the remote past. There was intermittent twitching on the right side of the face. Pronator drift was present on the right side of the body; the motor examination was otherwise normal, as were examinations of sensation and deep-tendon reflexes. Finger–nose–finger movements were smooth and accurate bilaterally after the patient understood the task. The stance and stride were normal, but the patient walked slowly and was unable to walk with a tandem gait or on his toes or heels. The Romberg test was negative.

Figure 1.

Clinical Photographs of Skin Lesions.
Table 1.

Laboratory Data.
Examination of the skin revealed a purple-brown scaly papule (0.5 cm in diameter) on the medial left knee (Figure 1A), a nonblanching purple-brown patch (1.5 cm in diameter) on the medial aspect of the left palmar foot (Figure 1B), and purple macules on the hard and soft palates. There were also multiple erythematous scars, including one on the left arm with an area of hard scale at the periphery; a red plaque (3 cm in diameter) on the chest with heaped-up central scale, hemorrhagic crust, and purulent discharge; a red plaque (4 cm in diameter) on the left flank with focal areas of scale and brown crust; gritty papules on the face; a large scaly red plaque on the back; and flaky scale on the scalp. The remainder of the physical examination was normal. The red-cell indexes, anion gap, and results of renal-function tests were normal, as were blood levels of calcium, phosphorus, magnesium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, vitamin B12, and thyrotropin. Urinalysis showed 1+ leukocyte esterase, 1+ bacteria, a pH of 6.0, and a specific gravity of 1.014; there were 3 to 5 red cells and 10 to 20 white cells per high-power field. Urine and blood toxicology screens were negative. Other laboratory test results are shown in Table 1.

Figure 2.

CT Scan of the Head.
Dr. R. Gilberto Gonzalez: Computed tomography of the head revealed ill-defined hypodensities in the white matter of the frontal lobes, which extended into the genu of the corpus callosum, and in the posterior periventricular white matter (Figure 2A). There was also an extraaxial calcification (4 cm in diameter) overlying the right frontal lobe that was thought to possibly represent a partially calcified meningioma (Figure 2B).

Dr. Goldstein: Six hours after the patient arrived in the emergency department, he had a 2-minute episode of aphasia. The temperature was 38.2°C. Ceftriaxone, vancomycin, acyclovir, and levetiracetam were administered intravenously, and additional imaging studies were obtained.

Figure 3.

MRI of the Head.
Dr. Gonzalez: Magnetic resonance imaging (MRI) of the head was performed with and without the administration of intravenous contrast material (Figure 3). T2-weighted images showed an abnormal hyperintense signal in the frontoparietal white matter that was slightly more prominent in the right frontal lobe than in the left frontal lobe and that extended into the genu of the corpus callosum; there was no local mass effect or abnormal restricted diffusion. There was also a small exophytic hypointense lesion along the inner table of the right frontal bone that was suggestive of a small calcified meningioma, as well as mild bilateral prominence of the parotid glands, which had restricted diffusion.

Dr. Goldstein: After the MRI, the patient had another 2-minute witnessed episode, during which he was staring, twitching, and unable to speak; afterward, he seemed to be more confused than he had been previously. A lumbar puncture was performed. The opening pressure was 9 cm of water, and the cerebrospinal fluid (CSF) was clear and colorless, without xanthochromia. Examination of the CSF revealed 4 red cells and 7 white cells per microliter, a white-cell differential count of 80% lymphocytes and 20% monocytes, a protein level of 97 mg per deciliter (reference range, 5 to 55), and a glucose level of 53 mg per deciliter (2.9 mmol per liter [reference range, 50 to 75 mg per deciliter; 2.8 to 4.2 mmol per liter]). Gram’s staining revealed moderate mononuclear cells, very rare polymorphonuclear leukocytes, and no organisms.

The patient was admitted to the hospital. On examination, there was tender inguinal lymphadenopathy on the left side. Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                    A 48-year-old man was seen in the emergency department of this hospital because of confusion.

The week before this presentation, the patient, who was a lawyer, had traveled alone to Mexico for vacation. His family reported that he seemed to be in his usual health before the trip but that, when they spoke with him by telephone while he was in Mexico (4 days before this presentation), he seemed euphoric and easily distracted, which were notable changes from baseline. They were then unable to reach him by telephone for 72 hours and became increasingly concerned about his well-being. Ultimately, he was reached by telephone; he was agitated and refused to board his scheduled return flight. The patient’s mother traveled from the United States to Mexico, where she found the patient to be confused and unkempt and to have lost his wallet and passport; he was drinking alcohol and insisting that he needed to travel immediately to New York City to work on an important legal case. His mother escorted him on a flight back to the United States and brought him to the emergency department of this hospital for evaluation.

In the emergency department, family members reported that the patient had begun having unexplained weight loss approximately 1 year earlier. The patient reported a history of multiple nonmelanoma skin cancers that had been treated with cryotherapy; he had also adopted a diet low in added sugar, which he believed had led to improvement in the appearance of the skin lesions. He had undergone sigmoidoscopy 12 years earlier to remove a foreign body from the sigmoid colon. He took melatonin and was allergic to penicillin. He was single, lived alone in an urban area of New England, and frequently traveled to Mexico; he had sex with men and used condoms intermittently. He drank alcohol in moderation and did not smoke or use illicit drugs. There was no family history of dementia, stroke, seizure disorder, cancer, depression, bipolar disorder, or schizophrenia.

On examination, the patient appeared thin and agitated. The temperature was 35.8°C, the pulse 71 beats per minute, the blood pressure 120/62 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. He was alert and oriented to which city he was in and to the year but not the month. When he was asked why he was in the emergency department, his response revealed anosognosia and confabulation. He had nonfluent aphasia and perseverated when speaking, but he had no dysarthria and was able to repeat words, name objects and the current president, and pantomime brushing his hair and teeth. He performed simple calculations accurately but was unable to perform two-part commands; he was slow when he spelled “table” and “world” backward and when he counted down from 100 in increments of 7. He could not provide abstract explanations for proverbs.

Examination of the function of cranial nerves II through XII revealed left-eye ptosis, a finding that was also visible on the patient’s driver’s license photograph, which had been taken in the remote past. There was intermittent twitching on the right side of the face. Pronator drift was present on the right side of the body; the motor examination was otherwise normal, as were examinations of sensation and deep-tendon reflexes. Finger–nose–finger movements were smooth and accurate bilaterally after the patient understood the task. The stance and stride were normal, but the patient walked slowly and was unable to walk with a tandem gait or on his toes or heels. The Romberg test was negative.

Figure 1.

Clinical Photographs of Skin Lesions.
Table 1.

Laboratory Data.
Examination of the skin revealed a purple-brown scaly papule (0.5 cm in diameter) on the medial left knee (Figure 1A), a nonblanching purple-brown patch (1.5 cm in diameter) on the medial aspect of the left palmar foot (Figure 1B), and purple macules on the hard and soft palates. There were also multiple erythematous scars, including one on the left arm with an area of hard scale at the periphery; a red plaque (3 cm in diameter) on the chest with heaped-up central scale, hemorrhagic crust, and purulent discharge; a red plaque (4 cm in diameter) on the left flank with focal areas of scale and brown crust; gritty papules on the face; a large scaly red plaque on the back; and flaky scale on the scalp. The remainder of the physical examination was normal. The red-cell indexes, anion gap, and results of renal-function tests were normal, as were blood levels of calcium, phosphorus, magnesium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, vitamin B12, and thyrotropin. Urinalysis showed 1+ leukocyte esterase, 1+ bacteria, a pH of 6.0, and a specific gravity of 1.014; there were 3 to 5 red cells and 10 to 20 white cells per high-power field. Urine and blood toxicology screens were negative. Other laboratory test results are shown in Table 1.

Figure 2.

CT Scan of the Head.
Dr. R. Gilberto Gonzalez: Computed tomography of the head revealed ill-defined hypodensities in the white matter of the frontal lobes, which extended into the genu of the corpus callosum, and in the posterior periventricular white matter (Figure 2A). There was also an extraaxial calcification (4 cm in diameter) overlying the right frontal lobe that was thought to possibly represent a partially calcified meningioma (Figure 2B).

Dr. Goldstein: Six hours after the patient arrived in the emergency department, he had a 2-minute episode of aphasia. The temperature was 38.2°C. Ceftriaxone, vancomycin, acyclovir, and levetiracetam were administered intravenously, and additional imaging studies were obtained.

Figure 3.

MRI of the Head.
Dr. Gonzalez: Magnetic resonance imaging (MRI) of the head was performed with and without the administration of intravenous contrast material (Figure 3). T2-weighted images showed an abnormal hyperintense signal in the frontoparietal white matter that was slightly more prominent in the right frontal lobe than in the left frontal lobe and that extended into the genu of the corpus callosum; there was no local mass effect or abnormal restricted diffusion. There was also a small exophytic hypointense lesion along the inner table of the right frontal bone that was suggestive of a small calcified meningioma, as well as mild bilateral prominence of the parotid glands, which had restricted diffusion.

Dr. Goldstein: After the MRI, the patient had another 2-minute witnessed episode, during which he was staring, twitching, and unable to speak; afterward, he seemed to be more confused than he had been previously. A lumbar puncture was performed. The opening pressure was 9 cm of water, and the cerebrospinal fluid (CSF) was clear and colorless, without xanthochromia. Examination of the CSF revealed 4 red cells and 7 white cells per microliter, a white-cell differential count of 80% lymphocytes and 20% monocytes, a protein level of 97 mg per deciliter (reference range, 5 to 55), and a glucose level of 53 mg per deciliter (2.9 mmol per liter [reference range, 50 to 75 mg per deciliter; 2.8 to 4.2 mmol per liter]). Gram’s staining revealed moderate mononuclear cells, very rare polymorphonuclear leukocytes, and no organisms.

The patient was admitted to the hospital. On examination, there was tender inguinal lymphadenopathy on the left side. Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Neurosyphilis and secondary syphilis\n\nThe patient's symptoms of confusion, aphasia, and other neurological symptoms, along with his skin lesions and history of unprotected sex, suggest a sexually transmitted infection. The skin lesions are consistent with those seen in secondary syphilis. The neurological symptoms and the abnormalities seen on the CT and MRI scans of the brain suggest neurosyphilis, which is a complication of untreated syphilis that affects the brain and spinal cord. The patient's CSF results also support this diagnosis, as neurosyphilis can cause an elevated protein level and a slight increase in white blood cells in the CSF.""
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        ""content"": ""The patient's symptoms of confusion, aphasia, and agitation, along with his recent travel to Mexico and intermittent condom use, suggest a possible infectious cause. The skin lesions, weight loss, and the findings on the CT and MRI scans of the head further support this. The patient's CSF results show a slightly elevated protein level and a normal glucose level, which can be seen in viral, bacterial, fungal, and parasitic infections, as well as in non-infectious conditions such as malignancy and autoimmune disease. However, the patient's history and presentation make an infectious cause more likely. The patient's skin lesions are consistent with Kaposi's sarcoma, a type of cancer that commonly affects people with HIV. The patient's history of multiple sexual partners and inconsistent condom use put him at risk for HIV. HIV can cause neurological symptoms like the ones this patient is experiencing, especially if the patient has developed AIDS. \n\nDiagnosis: HIV/AIDS with Kaposi's sarcoma and neurological involvement.""
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        ""content"": ""The patient is a 48-year-old man presenting with confusion, agitation, and changes in behavior. He has a history of multiple nonmelanoma skin cancers and unexplained weight loss. On examination, he has left-eye ptosis, intermittent twitching on the right side of the face, and pronator drift on the right side of the body. He also has multiple skin lesions. His laboratory results show an elevated white blood cell count and an elevated erythrocyte sedimentation rate. His CT scan shows hypodensities in the white matter of the frontal lobes and an extraaxial calcification overlying the right frontal lobe. His MRI shows an abnormal hyperintense signal in the frontoparietal white matter and a small exophytic hypointense lesion along the inner table of the right frontal bone. His CSF analysis shows elevated protein and a white-cell differential count of 80% lymphocytes and 20% monocytes. \n\nThe differential diagnosis for this patient includes neurosyphilis, HIV-associated dementia, meningitis, and a brain tumor. The patient's history of multiple nonmelanoma skin cancers and unexplained weight loss could suggest an underlying immunodeficiency, such as HIV. His skin lesions could be Kaposi's sarcoma, which is associated with HIV. His neurological symptoms could be due to HIV-associated dementia or neurosyphilis, both of which can occur in patients with HIV. His elevated white blood cell count and erythrocyte sedimentation rate could suggest an infection, such as meningitis. His CT and MRI findings could suggest a brain tumor. \n\nHowever, the patient's CSF analysis does not show a high number of white blood cells, which would be expected in meningitis. His neurological symptoms and imaging findings are not typical for a brain tumor. His skin lesions do not look like Kaposi's sarcoma. Therefore, the most likely diagnosis is neurosyphilis or HIV-associated dementia. Given the patient's history of intermittent condom use and his skin lesions, the most likely diagnosis is neurosyphilis in the setting of HIV infection.\n\nDiagnosis: Neurosyphilis in the setting of HIV infection.""
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10.1056/NEJMcpc1701762,Case 19-2017 — A 53-Year-Old Woman with Leg Numbness and Weakness,,Diffuse large B-cell lymphoma consistent with neurolymphomatosis.,"Lymphomatous meningitis, most likely due to primary leptomeningeal lymphoma.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:       A 53-year-old woman with rheumatoid arthritis was admitted to this hospital because of progressive asymmetric hypoesthesia and weakness in the legs.

The patient had been in her usual health until 4 months before this admission, when hypoesthesia developed in the lateral aspect of the left foot. During the following 2 days, the hypoesthesia spread to involve the toes and midfoot. On evaluation by her primary care physician, the patient reported that her chronic low-back pain, which radiated to the buttocks, had increased in intensity, but there was no pain in the legs, fever, weight loss, or bowel or bladder changes. On neurologic examination, perception of light touch and pinprick was absent on the left toes and left forefoot; the remainder of the examination was normal. The erythrocyte sedimentation rate and blood levels of vitamin B12, glycated hemoglobin, and thyrotropin were normal. The patient was referred to the neurology clinic of this hospital for further evaluation.

During the next 5 days, hypoesthesia progressed to involve the proximal portion of the left foot, as well as the ankle and the lateral lower leg. The patient was evaluated in the outpatient neurology clinic, where she reported gradual progression of hypoesthesia involving the left leg but no pain or bowel or bladder incontinence. She was alert, cooperative, and articulate; she appeared well and was afebrile. Results of cranial-nerve examinations were normal (although the first cranial nerve was not tested). Strength was 4+ out of 5 during flexion and extension of the toes on the left foot, dorsiflexion and plantar flexion of the left ankle, eversion and inversion of the left foot, and flexion of the left knee; otherwise, strength was 5 out of 5. Perception of vibration was markedly diminished at the left hallux. Perception of light touch and pinprick was decreased on the left foot and the left lateral leg. Deep-tendon reflexes of the arms and legs were normal. The plantar reflex was flexor on the right side and absent on the left side. The remainder of the examination was normal. The patient was referred for nerve-conduction studies.

Dr. Michael P. Bowley: Seven days later (3 months before this admission), nerve-conduction studies were performed. The sensory and motor responses were normal and symmetric, and F-wave minimal latencies in the tibial nerves were normal. Hoffman’s reflex (or H reflex, which is the electrophysiological correlate of the Achilles’ deep-tendon reflex) was absent at the left soleus and normal at the right soleus. Needle electromyography of the left leg showed diminished recruitment of long-duration, polyphasic motor-unit potentials in proximal and distal muscles of the L5 myotome. Results of electromyography of the right leg were normal. On the basis of these findings, imaging studies were obtained.

Figure 1.

MRI of the Lumbar Spine, Obtained 3 Months before Admission.
Dr. William A. Mehan, Jr.: Magnetic resonance imaging (MRI) of the lumbar spine, performed with and without the administration of contrast material, revealed disk protrusions, hypertrophy of the ligamentum flavum, and facet arthropathy, processes that resulted in neural foraminal narrowing that was moderate on the left side at the level of L4–L5 and moderate to severe on both sides at the level of L5–S1. Nerve roots between the L3 and S1 levels had a thickened and clumped appearance and showed enhancement on contrast-enhanced images (Figure 1). Distal to the dorsal-root ganglia, the peripheral nerves were symmetric and did not show enhancement.

Table 1.

Cerebrospinal Fluid Analysis.
Dr. Spera: A lumbar puncture was performed for cerebrospinal fluid (CSF) analysis. Oligoclonal banding was not present in concentrated CSF. Cytologic studies of the CSF showed increased lymphocytes that were polymorphous and occasionally reactive and appeared to be benign. Immunophenotypic evaluation of the CSF did not reveal evidence of a monoclonal B-cell or unusual T-cell population; other test results are shown in Table 1. A provisional diagnosis of chronic inflammatory demyelinating polyneuropathy was made, and intravenous immune globulin was administered 4 weeks and 1 week before the patient was admitted to this hospital.

Despite the administration of intravenous immune globulin, symptoms in the left leg did not improve, and hypoesthesia and weakness developed in the right leg and progressed centripetally. The patient had several falls at home and began to use a cane, then a walker, and ultimately a wheelchair. When the patient was no longer able to stand from a seated position, she presented to the emergency department of this hospital for evaluation.

On evaluation in the emergency department, the patient reported episodes of bowel and bladder incontinence that she attributed to leg weakness interfering with her ability to walk to the bathroom quickly. She reported no fevers, weight loss, or night sweats. Rheumatoid arthritis had been diagnosed 18 months before this admission, and therapy with methotrexate and prednisone had been initiated. Because of persistent disease activity, therapy with etanercept was initiated 7 months before this admission, after an interferon-_ release assay for Mycobacterium tuberculosis had been negative. On serial computed tomographic (CT) scans of the chest, there were subcentimeter pulmonary nodules in the bilateral lower lobes that had remained unchanged over a period of 4 years. The patient also had gastroesophageal reflux disease, uterine fibroids, and _-thalassemia minor. Results of routine screening mammography performed 1 month before this admission were normal. Medications were omeprazole, methotrexate, prednisone, folic acid, gabapentin, and duloxetine. The patient had recently stopped taking etanercept, because she thought her progressive symptoms could be related to that medication. She resided in New England and worked in a health care environment in a nonclinical role. She had previously traveled to the southwestern United States. She was a current smoker with an 18-pack-year history of smoking, and she did not drink alcohol or use illicit drugs. Her sister had multiple sclerosis; there was no family history of cancer.

On examination, the temperature was 36.3°C, the blood pressure 168/78 mm Hg, the pulse 90 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. Motor strength was 4 out of 5 in both legs and 4+ out of 5 on both sides during hip flexion; the remainder of the motor examination was normal. Perception of vibration and temperature was markedly diminished in both legs from the toes to above the knees. Deep-tendon reflexes were 1+ and symmetric at the patellae and were absent at the soleus. The plantar reflex was absent on both sides. The patient was unable to stand without assistance. Two firm, nontender subcutaneous nodules (approximately 1 cm in diameter) with overlying excoriations were present in the left submandibular area. The remainder of the examination was normal.

Blood levels of electrolytes, glucose, C-reactive protein, and angiotensin-converting enzyme and results of kidney- and liver-function tests were normal. With the exception of the presence of a stable microcytic anemia, the complete blood count and white-cell differential count were normal. Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen, HIV type 1 and type 2 antibodies, and Treponema pallidum were negative. The patient was admitted to the hospital, and additional imaging studies were obtained.

Figure 2.

MRI of the Lumbar Spine and Head, Obtained on Admission.
Dr. Mehan: MRI of the spine was performed with and without the administration of contrast material (Figure 2A and 2B). Contrast-enhanced images showed diffuse, irregular, abnormal hyperintensity in the spinal cord that extended from T10 inferiorly to the conus; there was probable mild expansion of the spinal cord, diffuse abnormal signal throughout the spinal canal, marked thickening and enhancement of the nerve roots, and severe mass effect on the conus. MRI of the head was also performed with and without the administration of contrast material (Figure 2C and 2D). Contrast-enhanced images and fluid-attenuated inversion recovery images showed abnormal diffuse hyperintensity in the sulci of both hemispheres with no leptomeningeal enhancement; there were periventricular patchy, ill-defined foci of enhancement on both sides. CT of the chest revealed no clinically significant change in the previously identified pulmonary nodules and no lymphadenopathy.

Dr. Bowley: Repeat nerve-conduction studies revealed asymmetric attenuation in the amplitudes of sensory and motor responses (which was worse on the left side than on the right) and no evidence of primary demyelination. Electromyography showed abnormal spontaneous activity in the bilateral thoracic paraspinal muscles at the level of T8 and in the bilateral gluteus maximus, tensor fasciae latae, lateral gastrocnemius, and right tibialis anterior muscles. Diffusely diminished recruitment of normal-appearing motor-unit potentials was observed in all the muscles tested in both legs.

Dr. Spera: Repeat lumbar puncture was performed, and CSF analysis revealed a protein level of 4620 mg per deciliter and a glucose level lower than 2 mg per deciliter (0.1 mmol per liter). There were abundant lymphocytes that were polymorphous, enlarged, reactive, and atypical and were of uncertain clinical significance. Immunophenotypic evaluation of the CSF revealed B cells with indeterminate surface and cytoplasmic expression of kappa and lambda immunoglobulin light chains; other test results are shown in Table 1. Fine-needle aspiration of one of the submandibular nodules was performed but yielded insufficient material for pathological evaluation. Three induced-sputum samples were negative for acid-fast bacteria. Urinary retention, absence of rectal tone, and saddle anesthesia (loss of sensation in the area of the buttocks and perineum) developed. A diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:           A 53-year-old woman with rheumatoid arthritis was admitted to this hospital because of progressive asymmetric hypoesthesia and weakness in the legs.

The patient had been in her usual health until 4 months before this admission, when hypoesthesia developed in the lateral aspect of the left foot. During the following 2 days, the hypoesthesia spread to involve the toes and midfoot. On evaluation by her primary care physician, the patient reported that her chronic low-back pain, which radiated to the buttocks, had increased in intensity, but there was no pain in the legs, fever, weight loss, or bowel or bladder changes. On neurologic examination, perception of light touch and pinprick was absent on the left toes and left forefoot; the remainder of the examination was normal. The erythrocyte sedimentation rate and blood levels of vitamin B12, glycated hemoglobin, and thyrotropin were normal. The patient was referred to the neurology clinic of this hospital for further evaluation.

During the next 5 days, hypoesthesia progressed to involve the proximal portion of the left foot, as well as the ankle and the lateral lower leg. The patient was evaluated in the outpatient neurology clinic, where she reported gradual progression of hypoesthesia involving the left leg but no pain or bowel or bladder incontinence. She was alert, cooperative, and articulate; she appeared well and was afebrile. Results of cranial-nerve examinations were normal (although the first cranial nerve was not tested). Strength was 4+ out of 5 during flexion and extension of the toes on the left foot, dorsiflexion and plantar flexion of the left ankle, eversion and inversion of the left foot, and flexion of the left knee; otherwise, strength was 5 out of 5. Perception of vibration was markedly diminished at the left hallux. Perception of light touch and pinprick was decreased on the left foot and the left lateral leg. Deep-tendon reflexes of the arms and legs were normal. The plantar reflex was flexor on the right side and absent on the left side. The remainder of the examination was normal. The patient was referred for nerve-conduction studies.

Dr. Michael P. Bowley: Seven days later (3 months before this admission), nerve-conduction studies were performed. The sensory and motor responses were normal and symmetric, and F-wave minimal latencies in the tibial nerves were normal. Hoffman’s reflex (or H reflex, which is the electrophysiological correlate of the Achilles’ deep-tendon reflex) was absent at the left soleus and normal at the right soleus. Needle electromyography of the left leg showed diminished recruitment of long-duration, polyphasic motor-unit potentials in proximal and distal muscles of the L5 myotome. Results of electromyography of the right leg were normal. On the basis of these findings, imaging studies were obtained.

Figure 1.

MRI of the Lumbar Spine, Obtained 3 Months before Admission.
Dr. William A. Mehan, Jr.: Magnetic resonance imaging (MRI) of the lumbar spine, performed with and without the administration of contrast material, revealed disk protrusions, hypertrophy of the ligamentum flavum, and facet arthropathy, processes that resulted in neural foraminal narrowing that was moderate on the left side at the level of L4–L5 and moderate to severe on both sides at the level of L5–S1. Nerve roots between the L3 and S1 levels had a thickened and clumped appearance and showed enhancement on contrast-enhanced images (Figure 1). Distal to the dorsal-root ganglia, the peripheral nerves were symmetric and did not show enhancement.

Table 1.

Cerebrospinal Fluid Analysis.
Dr. Spera: A lumbar puncture was performed for cerebrospinal fluid (CSF) analysis. Oligoclonal banding was not present in concentrated CSF. Cytologic studies of the CSF showed increased lymphocytes that were polymorphous and occasionally reactive and appeared to be benign. Immunophenotypic evaluation of the CSF did not reveal evidence of a monoclonal B-cell or unusual T-cell population; other test results are shown in Table 1. A provisional diagnosis of chronic inflammatory demyelinating polyneuropathy was made, and intravenous immune globulin was administered 4 weeks and 1 week before the patient was admitted to this hospital.

Despite the administration of intravenous immune globulin, symptoms in the left leg did not improve, and hypoesthesia and weakness developed in the right leg and progressed centripetally. The patient had several falls at home and began to use a cane, then a walker, and ultimately a wheelchair. When the patient was no longer able to stand from a seated position, she presented to the emergency department of this hospital for evaluation.

On evaluation in the emergency department, the patient reported episodes of bowel and bladder incontinence that she attributed to leg weakness interfering with her ability to walk to the bathroom quickly. She reported no fevers, weight loss, or night sweats. Rheumatoid arthritis had been diagnosed 18 months before this admission, and therapy with methotrexate and prednisone had been initiated. Because of persistent disease activity, therapy with etanercept was initiated 7 months before this admission, after an interferon-_ release assay for Mycobacterium tuberculosis had been negative. On serial computed tomographic (CT) scans of the chest, there were subcentimeter pulmonary nodules in the bilateral lower lobes that had remained unchanged over a period of 4 years. The patient also had gastroesophageal reflux disease, uterine fibroids, and _-thalassemia minor. Results of routine screening mammography performed 1 month before this admission were normal. Medications were omeprazole, methotrexate, prednisone, folic acid, gabapentin, and duloxetine. The patient had recently stopped taking etanercept, because she thought her progressive symptoms could be related to that medication. She resided in New England and worked in a health care environment in a nonclinical role. She had previously traveled to the southwestern United States. She was a current smoker with an 18-pack-year history of smoking, and she did not drink alcohol or use illicit drugs. Her sister had multiple sclerosis; there was no family history of cancer.

On examination, the temperature was 36.3°C, the blood pressure 168/78 mm Hg, the pulse 90 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. Motor strength was 4 out of 5 in both legs and 4+ out of 5 on both sides during hip flexion; the remainder of the motor examination was normal. Perception of vibration and temperature was markedly diminished in both legs from the toes to above the knees. Deep-tendon reflexes were 1+ and symmetric at the patellae and were absent at the soleus. The plantar reflex was absent on both sides. The patient was unable to stand without assistance. Two firm, nontender subcutaneous nodules (approximately 1 cm in diameter) with overlying excoriations were present in the left submandibular area. The remainder of the examination was normal.

Blood levels of electrolytes, glucose, C-reactive protein, and angiotensin-converting enzyme and results of kidney- and liver-function tests were normal. With the exception of the presence of a stable microcytic anemia, the complete blood count and white-cell differential count were normal. Blood tests for human immunodeficiency virus (HIV) type 1 p24 antigen, HIV type 1 and type 2 antibodies, and Treponema pallidum were negative. The patient was admitted to the hospital, and additional imaging studies were obtained.

Figure 2.

MRI of the Lumbar Spine and Head, Obtained on Admission.
Dr. Mehan: MRI of the spine was performed with and without the administration of contrast material (Figure 2A and 2B). Contrast-enhanced images showed diffuse, irregular, abnormal hyperintensity in the spinal cord that extended from T10 inferiorly to the conus; there was probable mild expansion of the spinal cord, diffuse abnormal signal throughout the spinal canal, marked thickening and enhancement of the nerve roots, and severe mass effect on the conus. MRI of the head was also performed with and without the administration of contrast material (Figure 2C and 2D). Contrast-enhanced images and fluid-attenuated inversion recovery images showed abnormal diffuse hyperintensity in the sulci of both hemispheres with no leptomeningeal enhancement; there were periventricular patchy, ill-defined foci of enhancement on both sides. CT of the chest revealed no clinically significant change in the previously identified pulmonary nodules and no lymphadenopathy.

Dr. Bowley: Repeat nerve-conduction studies revealed asymmetric attenuation in the amplitudes of sensory and motor responses (which was worse on the left side than on the right) and no evidence of primary demyelination. Electromyography showed abnormal spontaneous activity in the bilateral thoracic paraspinal muscles at the level of T8 and in the bilateral gluteus maximus, tensor fasciae latae, lateral gastrocnemius, and right tibialis anterior muscles. Diffusely diminished recruitment of normal-appearing motor-unit potentials was observed in all the muscles tested in both legs.

Dr. Spera: Repeat lumbar puncture was performed, and CSF analysis revealed a protein level of 4620 mg per deciliter and a glucose level lower than 2 mg per deciliter (0.1 mmol per liter). There were abundant lymphocytes that were polymorphous, enlarged, reactive, and atypical and were of uncertain clinical significance. Immunophenotypic evaluation of the CSF revealed B cells with indeterminate surface and cytoplasmic expression of kappa and lambda immunoglobulin light chains; other test results are shown in Table 1. Fine-needle aspiration of one of the submandibular nodules was performed but yielded insufficient material for pathological evaluation. Three induced-sputum samples were negative for acid-fast bacteria. Urinary retention, absence of rectal tone, and saddle anesthesia (loss of sensation in the area of the buttocks and perineum) developed. A diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Primary central nervous system lymphoma. The patient's symptoms of progressive asymmetric hypoesthesia and weakness in the legs, along with the MRI findings of diffuse, irregular, abnormal hyperintensity in the spinal cord and abnormal diffuse hyperintensity in the sulci of both hemispheres, suggest a central nervous system disorder. The presence of abundant lymphocytes in the CSF, some of which were atypical, suggests a lymphoproliferative disorder. The lack of improvement with intravenous immune globulin treatment makes a diagnosis of chronic inflammatory demyelinating polyneuropathy less likely. Primary central nervous system lymphoma is a rare type of non-Hodgkin lymphoma that starts in the brain, spinal cord, or eye.""
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        ""content"": ""Primary central nervous system lymphoma (PCNSL). The patient's symptoms of progressive asymmetric hypoesthesia and weakness in the legs, along with the MRI findings of diffuse, irregular, abnormal hyperintensity in the spinal cord and abnormal diffuse hyperintensity in the sulci of both hemispheres, suggest a central nervous system disorder. The CSF analysis showing abundant lymphocytes that were polymorphous, enlarged, reactive, and atypical, along with B cells with indeterminate surface and cytoplasmic expression of kappa and lambda immunoglobulin light chains, suggest a lymphoproliferative disorder. The combination of these findings is most consistent with PCNSL.""
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        ""content"": ""The patient is a 53-year-old woman with a history of rheumatoid arthritis who presents with progressive asymmetric hypoesthesia and weakness in the legs. The differential diagnosis for this patient includes multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, and neurosarcoidosis. The patient's sister has a history of multiple sclerosis, which could suggest a genetic predisposition. However, the patient's MRI does not show the characteristic lesions of multiple sclerosis, making this diagnosis less likely. The patient was initially diagnosed with chronic inflammatory demyelinating polyneuropathy, but her symptoms did not improve with intravenous immune globulin, which is the standard treatment for this condition. This makes chronic inflammatory demyelinating polyneuropathy less likely. The patient's MRI shows abnormal hyperintensity in the spinal cord and abnormal diffuse hyperintensity in the sulci of both hemispheres, which could be consistent with neurosarcoidosis. The patient also has a history of rheumatoid arthritis, another autoimmune condition, which could make her more susceptible to developing neurosarcoidosis. The patient's CSF analysis also shows abundant lymphocytes, which could be consistent with an inflammatory process like neurosarcoidosis. \n\nDiagnosis: Neurosarcoidosis.""
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10.1056/NEJMcpc1616394,Case 18-2017 — An 11-Year-Old Girl with Difficulty Eating after a Choking Incident,,Avoidant–restrictive food intake disorder (ARFID).,Avoidant–restrictive food intake disorder (ARFID).,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  An 11-year-old girl was seen in an outpatient clinic of this hospital because of difficulty eating solid food and associated weight loss after an acute choking incident.

The patient had been in her usual health until 14 days before this evaluation, when a piece of meat became stuck in an orthodontic palate expander that had been inserted 19 days earlier and she thought she might choke. She was able to dislodge the meat shortly thereafter, but during the next 7 days, she reportedly had an intense fear of swallowing, ate very carefully, and had an associated decrease in her food intake. On the 7th day after the choking incident, she stopped eating most solid foods; thereafter, she consumed only milkshakes, liquid dietary supplements, and, occasionally, yogurt and oatmeal. She reported that she was unable to eat solid food because she was “afraid I can’t chew it up enough to swallow it so I don’t choke” and “I don’t really know how to chew like I used to.” One day before this evaluation, her orthodontist removed the palate expander. However, the swallowing difficulty persisted; she was unable to swallow small pieces of chicken or a single grain of rice. On the day of this evaluation, the patient consumed only a spoonful of oatmeal (which she had previously been willing to eat), a half can of a liquid dietary supplement, and a small amount of water and juice. Her parents noted that she chewed food with her front teeth but appeared to be unable to move the food from the front of her mouth to the back to swallow it. Her weight had decreased by 1.4 kg since an examination performed 2 months earlier, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was below the 1st percentile. Her parents were worried about acute malnutrition and dehydration. They requested an urgent evaluation in the Eating Disorders Clinical and Research Program outpatient clinic at this hospital, and from there, the patient was referred to the Adolescent and Young Adult Medicine clinic at this hospital.

Figure 1.

The Patient’s Growth Chart and Body-Mass Index.
During a psychiatric evaluation of the patient, her parents reported that she had been a highly selective eater since infancy, had cried the first time she ate solid food, and had frequently required coaxing from her parents to complete meals. The patient disliked many foods (including artichokes, asparagus, meatballs, pasta sauce, hamburger buns, and sandwiches) because of their taste or texture or because they were “mixed together.” These strict preferences had severely limited the available food choices for the family’s dinners and affected the patient’s ability to socialize with friends. Her BMI had been as low as the one tenth percentile and had been consistently below the 1st percentile during recent years, including during her most recent examination 2 months earlier (Figure 1). Cyproheptadine had been administered the previous year but was stopped after only transient improvement in her appetite because of lethargy. The patient did not report that she felt fat; she noted, “If anything, I worry that I’m too skinny. I’m one of the smallest in my class,” and she stated her desired weight to be average or a little lower than average. She reported no history of binge eating, self-induced vomiting, or use of laxatives, diuretics, or diet pills. She also reported no symptoms of pica or rumination disorder, depression, anxiety disorders, phobias (besides fear of choking), substance abuse, post-traumatic stress disorder, attention-deficit–hyperactivity disorder, or oppositional defiant disorder. As a young child, she had constipation, for which she had been seen by a gastroenterologist at another hospital and had briefly received treatment with polyethylene glycol, fiber, and a stimulant laxative. She had been seen intermittently by nutritionists at another hospital since she was 6 years of age. At the other hospital, testing for celiac disease was reportedly negative. She took no medications currently and was allergic to penicillin, which had caused hives. She lived with her parents and younger siblings; she was a student who did well academically and had many friends and hobbies. There was a family history of depression.

Table 1.

Laboratory Data.
On medical examination, the temperature was 38°C, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air; the blood pressure and pulse were 107/70 mm Hg and 114 beats per minute while she was in the supine position and 95/72 mm Hg and 123 beats per minute while she was standing. The weight was 26.5 kg, and the BMI 12.5. There were no oral petechiae, and sexual development was classified as Tanner stage 2 (with stages ranging from 1 to 5 and higher stages indicating more advanced pubertal development); the remainder of the examination was normal. The hemoglobin level, hematocrit, platelet count, red-cell indexes, and results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, magnesium, total protein, globulin, and thyrotropin; other test results are shown in Table 1. Urinalysis revealed a specific gravity of higher than 1.030, a pH of 6.0, and 4+ ketones and 1+ protein by dipstick. An electrocardiogram showed sinus tachycardia at a rate of 110 beats per minute, with a PR interval of 116 msec, a corrected QT interval of 422 msec, and evidence of an incomplete right bundle-branch block.

The patient was admitted to this hospital. A diagnosis and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              An 11-year-old girl was seen in an outpatient clinic of this hospital because of difficulty eating solid food and associated weight loss after an acute choking incident.

The patient had been in her usual health until 14 days before this evaluation, when a piece of meat became stuck in an orthodontic palate expander that had been inserted 19 days earlier and she thought she might choke. She was able to dislodge the meat shortly thereafter, but during the next 7 days, she reportedly had an intense fear of swallowing, ate very carefully, and had an associated decrease in her food intake. On the 7th day after the choking incident, she stopped eating most solid foods; thereafter, she consumed only milkshakes, liquid dietary supplements, and, occasionally, yogurt and oatmeal. She reported that she was unable to eat solid food because she was “afraid I can’t chew it up enough to swallow it so I don’t choke” and “I don’t really know how to chew like I used to.” One day before this evaluation, her orthodontist removed the palate expander. However, the swallowing difficulty persisted; she was unable to swallow small pieces of chicken or a single grain of rice. On the day of this evaluation, the patient consumed only a spoonful of oatmeal (which she had previously been willing to eat), a half can of a liquid dietary supplement, and a small amount of water and juice. Her parents noted that she chewed food with her front teeth but appeared to be unable to move the food from the front of her mouth to the back to swallow it. Her weight had decreased by 1.4 kg since an examination performed 2 months earlier, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was below the 1st percentile. Her parents were worried about acute malnutrition and dehydration. They requested an urgent evaluation in the Eating Disorders Clinical and Research Program outpatient clinic at this hospital, and from there, the patient was referred to the Adolescent and Young Adult Medicine clinic at this hospital.

Figure 1.

The Patient’s Growth Chart and Body-Mass Index.
During a psychiatric evaluation of the patient, her parents reported that she had been a highly selective eater since infancy, had cried the first time she ate solid food, and had frequently required coaxing from her parents to complete meals. The patient disliked many foods (including artichokes, asparagus, meatballs, pasta sauce, hamburger buns, and sandwiches) because of their taste or texture or because they were “mixed together.” These strict preferences had severely limited the available food choices for the family’s dinners and affected the patient’s ability to socialize with friends. Her BMI had been as low as the one tenth percentile and had been consistently below the 1st percentile during recent years, including during her most recent examination 2 months earlier (Figure 1). Cyproheptadine had been administered the previous year but was stopped after only transient improvement in her appetite because of lethargy. The patient did not report that she felt fat; she noted, “If anything, I worry that I’m too skinny. I’m one of the smallest in my class,” and she stated her desired weight to be average or a little lower than average. She reported no history of binge eating, self-induced vomiting, or use of laxatives, diuretics, or diet pills. She also reported no symptoms of pica or rumination disorder, depression, anxiety disorders, phobias (besides fear of choking), substance abuse, post-traumatic stress disorder, attention-deficit–hyperactivity disorder, or oppositional defiant disorder. As a young child, she had constipation, for which she had been seen by a gastroenterologist at another hospital and had briefly received treatment with polyethylene glycol, fiber, and a stimulant laxative. She had been seen intermittently by nutritionists at another hospital since she was 6 years of age. At the other hospital, testing for celiac disease was reportedly negative. She took no medications currently and was allergic to penicillin, which had caused hives. She lived with her parents and younger siblings; she was a student who did well academically and had many friends and hobbies. There was a family history of depression.

Table 1.

Laboratory Data.
On medical examination, the temperature was 38°C, the respiratory rate 18 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air; the blood pressure and pulse were 107/70 mm Hg and 114 beats per minute while she was in the supine position and 95/72 mm Hg and 123 beats per minute while she was standing. The weight was 26.5 kg, and the BMI 12.5. There were no oral petechiae, and sexual development was classified as Tanner stage 2 (with stages ranging from 1 to 5 and higher stages indicating more advanced pubertal development); the remainder of the examination was normal. The hemoglobin level, hematocrit, platelet count, red-cell indexes, and results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, magnesium, total protein, globulin, and thyrotropin; other test results are shown in Table 1. Urinalysis revealed a specific gravity of higher than 1.030, a pH of 6.0, and 4+ ketones and 1+ protein by dipstick. An electrocardiogram showed sinus tachycardia at a rate of 110 beats per minute, with a PR interval of 116 msec, a corrected QT interval of 422 msec, and evidence of an incomplete right bundle-branch block.

The patient was admitted to this hospital. A diagnosis and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Avoidant/Restrictive Food Intake Disorder (ARFID). This patient presents with a history of selective eating, recent choking incident, and subsequent fear of swallowing leading to decreased food intake and weight loss. The differential diagnosis includes eating disorders such as anorexia nervosa, bulimia nervosa, and ARFID, as well as medical conditions such as eosinophilic esophagitis, gastroesophageal reflux disease (GERD), and dysphagia due to neurological or structural abnormalities. Anorexia and bulimia are less likely as the patient does not express a fear of weight gain, does not engage in binge eating or purging behaviors, and expresses a desire to gain weight. Eosinophilic esophagitis and GERD typically present with chronic symptoms of dysphagia or heartburn, which this patient does not report. Neurological or structural abnormalities causing dysphagia would likely have been present prior to the choking incident. The patient's intense fear of choking, selective eating habits, and avoidance of food due to its texture or taste are characteristic of ARFID.""
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10.1056/NEJMcpc1616019,Case 17-2017 — A 14-Year-Old Boy with Acute Fear of Choking while Swallowing,,Pseudohypoparathyroidism type 1b.,Pseudohypoparathyroidism type 1b.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                    A 14-year-old boy was seen in the emergency department of this hospital because of fear of choking while swallowing.

The patient had been well until 2 days before admission, when he choked while eating a piece of chicken during dinner. He became fearful of swallowing and was unable to finish the meal despite cutting his food into small pieces. The next day, he vomited after trying to eat ice cream, and his daily fluid intake decreased to only 710 ml (24 oz) of water. He reportedly needed his mother near him throughout the day and had an “irrational fear” of choking. He had not had recent fevers, rhinorrhea, cough, or sore throat. Nine days earlier, during a routine annual examination at the clinic of the patient’s primary care pediatrician, the patient’s mother reported that he had had several episodes of inspiratory stridor while he was sleeping during the past few weeks; the patient was referred to an otolaryngologist, but this visit had not yet occurred. On the day of this presentation, the patient consumed only small sips of water, reported feeling hungry, and slept most of the day. His mother noted that, in addition to the inspiratory stridor during sleep, the patient had some gasping for air that was associated with deep involuntary burping. She contacted a physician at this hospital and was advised to bring the patient to the emergency department for evaluation.

The patient had been delivered at full term. He had a nuchal cord at birth, and the birth weight was 3.6 kg. Apgar scores at 1, 5, and 10 minutes were 2, 6, and 9, respectively, and initial resuscitation efforts were provided. Subsequent growth and development were reportedly normal. As an infant, the patient had had gastroesophageal reflux and a milk-protein allergy, and he had received some training on sensory-integration skills during childhood. Immunizations had been administered through 2.5 years of age; after that age, the recommended routine vaccinations were refused by the patient’s parents. The patient had keratosis pilaris and eczema. He took no medications and had no known allergies. He lived with his family in a suburb and was a student who received writing support. His younger brother had moderate autism spectrum disorder, with verbal (but not conversational) skills, and had received diagnoses of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) and vitamin D deficiency. Both parents were healthy. The patient’s maternal grandfather had heart disease and non–insulin-dependent diabetes mellitus, his maternal grandmother had had psoriasis and had died from breast cancer, an aunt had hypoglycemia, and his paternal grandmother had hypertension, hypoglycemia, and congestive heart failure.

Table 1.

Laboratory Data.
On examination in the emergency department, the patient was alert and appeared to be anxious. He had persistent involuntary burping, with evidence of drooling on his shirt. The temperature was 36.1°C, the blood pressure 127/64 mm Hg, the pulse 67 beats per minute, the respiratory rate 18 breaths per minute, the weight 54.1 kg (60th percentile for his age), and the height 160 cm (32nd percentile for his age). The oral mucosal membranes were dry. Sexual development was classified as Tanner stage 4 (with stages ranging from 1 to 5 and higher stages indicating more advanced pubertal development). Results of examinations of cranial nerves II through XII were normal. The patient spoke clearly, and his gait, strength, sensation, and deep-tendon reflexes in the arms and legs were normal. The remainder of the examination was also normal. His initial laboratory studies revealed profound hypocalcemia and hyperphosphatemia, but other laboratory test results were normal, including blood levels of alanine aminotransferase, aspartate aminotransferase, amylase, and lipase, as well as titers of antistreptolysin O and anti-DNase B; other test results are shown in Table 1. An electrocardiogram showed a normal sinus rhythm with no acute ischemic changes. The corrected QT interval was reportedly mildly prolonged, at 471 msec.

Because the patient had severe, symptomatic hypocalcemia, he was admitted to the pediatric intensive care unit (ICU) for cardiovascular and respiratory monitoring and supportive care. On examination, he refused to swallow, had persistent burping, and stated, “I don’t want to die.” The leg muscles were hypertonic. On examination performed by a pediatric endocrinology consultant, a mildly positive Chvostek’s sign (twitching of the facial muscles) was elicited on the left side in response to tapping on the region of the facial nerve anterior to the external auditory canal.

Additional diagnostic tests were performed.

Initial Management
Dr. Ryan W. Carroll: My colleagues will address the differential diagnosis of this patient’s overall presentation. However, I would like to highlight the aspects of this case that were potentially life-threatening.

This patient’s fear of swallowing suggested the possibility of airway compromise, which can lead to respiratory insufficiency. We were immediately concerned about mechanical obstruction due to a neoplasm that involved the tissue of the neck (e.g., sarcoma, rhabdomyosarcoma, or lymphoma), an infectious process (e.g., a retropharyngeal or tonsillar abscess), a cystic lesion, or subglottic stenosis or web. We also considered the possibility of neuromuscular dysfunction due to rabies, increased intracranial pressure or mass effect of the posterior fossa (both of which can lead to vocal-cord dysfunction), the Miller Fisher variant of the Guillain–Barré syndrome, a variant of Bell’s palsy, or severely altered electrolyte levels. In this case, the patient did not have frank stridor or respiratory distress, and the sensation of being at risk for choking was most likely caused by profound hypocalcemia.

In the ICU, we considered the potential life-threatening effects of severe hypocalcemia. Hypocalcemia has the potential to lead to seizures, tetany that results in respiratory insufficiency or failure, rhabdomyolysis, acute kidney injury, electrocardiographic alterations (e.g., a prolonged QT interval), bradycardia, and myocardial dysfunction. We also considered underlying illnesses that result in profound hypocalcemia, which can lead to or reflect other grave complications. These include phosphorus overdose, hyperphosphatemia due to rhabdomyolysis or tumor lysis, chronic kidney disease, recent use of an extracorporeal circuit (i.e., plasmapheresis or renal-replacement therapy) that required citrate anticoagulation, infusion of EDTA, massive transfusion of blood products anticoagulated with citrate, genetic syndromes that harbor additional complications (e.g., the DiGeorge syndrome), sepsis, hepatic dysfunction, the use of medications that increase the activity of cytochrome P-450, and pancreatic dysfunction or frank pancreatitis.

The initial treatment of this patient included respiratory and cardiovascular monitoring and calcium repletion. Although his blood pressure was elevated at the time of admission, it returned to normal on the third hospital day, which suggests that the elevation might have been due to anxiety. The patient did not ultimately need respiratory assistance, and his symptoms dramatically improved as his blood calcium level increased.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                A 14-year-old boy was seen in the emergency department of this hospital because of fear of choking while swallowing.

The patient had been well until 2 days before admission, when he choked while eating a piece of chicken during dinner. He became fearful of swallowing and was unable to finish the meal despite cutting his food into small pieces. The next day, he vomited after trying to eat ice cream, and his daily fluid intake decreased to only 710 ml (24 oz) of water. He reportedly needed his mother near him throughout the day and had an “irrational fear” of choking. He had not had recent fevers, rhinorrhea, cough, or sore throat. Nine days earlier, during a routine annual examination at the clinic of the patient’s primary care pediatrician, the patient’s mother reported that he had had several episodes of inspiratory stridor while he was sleeping during the past few weeks; the patient was referred to an otolaryngologist, but this visit had not yet occurred. On the day of this presentation, the patient consumed only small sips of water, reported feeling hungry, and slept most of the day. His mother noted that, in addition to the inspiratory stridor during sleep, the patient had some gasping for air that was associated with deep involuntary burping. She contacted a physician at this hospital and was advised to bring the patient to the emergency department for evaluation.

The patient had been delivered at full term. He had a nuchal cord at birth, and the birth weight was 3.6 kg. Apgar scores at 1, 5, and 10 minutes were 2, 6, and 9, respectively, and initial resuscitation efforts were provided. Subsequent growth and development were reportedly normal. As an infant, the patient had had gastroesophageal reflux and a milk-protein allergy, and he had received some training on sensory-integration skills during childhood. Immunizations had been administered through 2.5 years of age; after that age, the recommended routine vaccinations were refused by the patient’s parents. The patient had keratosis pilaris and eczema. He took no medications and had no known allergies. He lived with his family in a suburb and was a student who received writing support. His younger brother had moderate autism spectrum disorder, with verbal (but not conversational) skills, and had received diagnoses of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) and vitamin D deficiency. Both parents were healthy. The patient’s maternal grandfather had heart disease and non–insulin-dependent diabetes mellitus, his maternal grandmother had had psoriasis and had died from breast cancer, an aunt had hypoglycemia, and his paternal grandmother had hypertension, hypoglycemia, and congestive heart failure.

Table 1.

Laboratory Data.
On examination in the emergency department, the patient was alert and appeared to be anxious. He had persistent involuntary burping, with evidence of drooling on his shirt. The temperature was 36.1°C, the blood pressure 127/64 mm Hg, the pulse 67 beats per minute, the respiratory rate 18 breaths per minute, the weight 54.1 kg (60th percentile for his age), and the height 160 cm (32nd percentile for his age). The oral mucosal membranes were dry. Sexual development was classified as Tanner stage 4 (with stages ranging from 1 to 5 and higher stages indicating more advanced pubertal development). Results of examinations of cranial nerves II through XII were normal. The patient spoke clearly, and his gait, strength, sensation, and deep-tendon reflexes in the arms and legs were normal. The remainder of the examination was also normal. His initial laboratory studies revealed profound hypocalcemia and hyperphosphatemia, but other laboratory test results were normal, including blood levels of alanine aminotransferase, aspartate aminotransferase, amylase, and lipase, as well as titers of antistreptolysin O and anti-DNase B; other test results are shown in Table 1. An electrocardiogram showed a normal sinus rhythm with no acute ischemic changes. The corrected QT interval was reportedly mildly prolonged, at 471 msec.

Because the patient had severe, symptomatic hypocalcemia, he was admitted to the pediatric intensive care unit (ICU) for cardiovascular and respiratory monitoring and supportive care. On examination, he refused to swallow, had persistent burping, and stated, “I don’t want to die.” The leg muscles were hypertonic. On examination performed by a pediatric endocrinology consultant, a mildly positive Chvostek’s sign (twitching of the facial muscles) was elicited on the left side in response to tapping on the region of the facial nerve anterior to the external auditory canal.

Additional diagnostic tests were performed.

Initial Management
Dr. Ryan W. Carroll: My colleagues will address the differential diagnosis of this patient’s overall presentation. However, I would like to highlight the aspects of this case that were potentially life-threatening.

This patient’s fear of swallowing suggested the possibility of airway compromise, which can lead to respiratory insufficiency. We were immediately concerned about mechanical obstruction due to a neoplasm that involved the tissue of the neck (e.g., sarcoma, rhabdomyosarcoma, or lymphoma), an infectious process (e.g., a retropharyngeal or tonsillar abscess), a cystic lesion, or subglottic stenosis or web. We also considered the possibility of neuromuscular dysfunction due to rabies, increased intracranial pressure or mass effect of the posterior fossa (both of which can lead to vocal-cord dysfunction), the Miller Fisher variant of the Guillain–Barré syndrome, a variant of Bell’s palsy, or severely altered electrolyte levels. In this case, the patient did not have frank stridor or respiratory distress, and the sensation of being at risk for choking was most likely caused by profound hypocalcemia.

In the ICU, we considered the potential life-threatening effects of severe hypocalcemia. Hypocalcemia has the potential to lead to seizures, tetany that results in respiratory insufficiency or failure, rhabdomyolysis, acute kidney injury, electrocardiographic alterations (e.g., a prolonged QT interval), bradycardia, and myocardial dysfunction. We also considered underlying illnesses that result in profound hypocalcemia, which can lead to or reflect other grave complications. These include phosphorus overdose, hyperphosphatemia due to rhabdomyolysis or tumor lysis, chronic kidney disease, recent use of an extracorporeal circuit (i.e., plasmapheresis or renal-replacement therapy) that required citrate anticoagulation, infusion of EDTA, massive transfusion of blood products anticoagulated with citrate, genetic syndromes that harbor additional complications (e.g., the DiGeorge syndrome), sepsis, hepatic dysfunction, the use of medications that increase the activity of cytochrome P-450, and pancreatic dysfunction or frank pancreatitis.

The initial treatment of this patient included respiratory and cardiovascular monitoring and calcium repletion. Although his blood pressure was elevated at the time of admission, it returned to normal on the third hospital day, which suggests that the elevation might have been due to anxiety. The patient did not ultimately need respiratory assistance, and his symptoms dramatically improved as his blood calcium level increased.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Hypoparathyroidism\n\nThe patient's symptoms of fear of choking, persistent involuntary burping, and dry oral mucosal membranes, along with the laboratory findings of profound hypocalcemia and hyperphosphatemia, suggest a disorder of calcium metabolism. The patient's refusal to swallow and persistent burping could be due to laryngospasm or bronchospasm, which are symptoms of hypocalcemia. The presence of a mildly positive Chvostek\u2019s sign, which is a clinical sign of tetany seen in hypocalcemia, further supports this diagnosis. Hypoparathyroidism, a condition characterized by insufficient parathyroid hormone leading to low calcium and high phosphate levels in the blood, is the most likely diagnosis.""
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        ""content"": ""Hypoparathyroidism\n\nThe patient's symptoms of fear of choking, persistent burping, and refusal to swallow, along with the physical findings of dry oral mucosal membranes and hypertonic leg muscles, could be indicative of a neuromuscular issue. However, the laboratory findings of profound hypocalcemia and hyperphosphatemia are key in this diagnosis. Hypocalcemia can cause neuromuscular symptoms such as muscle cramps, spasms, and in severe cases, laryngospasm which could explain the patient's fear of choking. The presence of a positive Chvostek's sign, which is a clinical sign of existing nerve hyperexcitability seen in hypocalcemia, further supports this diagnosis. Hypoparathyroidism, a condition in which the body produces insufficient amounts of parathyroid hormone leading to low calcium and high phosphate levels in the blood, is the most likely cause of these findings.""
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        ""content"": ""The patient is a 14-year-old boy presenting with fear of choking while swallowing, inspiratory stridor during sleep, and involuntary burping. He also has a history of gastroesophageal reflux and a milk-protein allergy. The differential diagnosis for this patient includes psychogenic dysphagia, gastroesophageal reflux disease (GERD), eosinophilic esophagitis, and hypocalcemia. Psychogenic dysphagia is a possibility given the patient's fear of choking and the absence of physical abnormalities. However, this does not explain the patient's inspiratory stridor during sleep or his profound hypocalcemia. GERD could explain the patient's fear of choking and inspiratory stridor during sleep, but it does not explain the hypocalcemia. Eosinophilic esophagitis could also explain the patient's symptoms, but it does not explain the hypocalcemia. The patient's profound hypocalcemia could explain all of his symptoms, including the fear of choking, inspiratory stridor during sleep, and involuntary burping. Hypocalcemia can cause laryngospasm, which could lead to the patient's fear of choking and inspiratory stridor. It can also cause muscle spasms, which could lead to the involuntary burping. The patient's symptoms improved dramatically as his blood calcium level increased, further supporting the diagnosis of hypocalcemia.\n\nDiagnosis: Hypocalcemia.""
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10.1056/NEJMcpc1616398,Case 16-2017 — A 69-Year-Old Woman with Urinary Incontinence,,"Leiomyosarcoma, high grade, conventional type.",Uterine leiomyosarcoma.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 69-year-old woman was evaluated at the gynecologic oncology clinic of this hospital because of persistent urinary incontinence.

Seven years before this evaluation, the patient had received a diagnosis of superficial bladder cancer (low grade), for which a transurethral resection was performed. During the next 5 years, urologic evaluation with annual surveillance cystoscopy revealed no evidence of recurrent disease. Urination occurred frequently and urgently, and tolterodine was administered as needed for symptom control.

Twenty-one months before the current evaluation, the patient was seen by a urogynecologist for persistent urinary incontinence that occurred with bending over, coughing, and sneezing. Urination occurred up to 12 times daily and twice nightly. The patient reported no hematuria, dysuria, incomplete voiding, high fluid intake, pelvic or vaginal pressure or heaviness, prolapse, or fecal incontinence.

On an examination that was limited to the pelvis, the uterus was estimated to be similar in size to the uterus of a pregnant woman at 12 weeks of gestation. The uterus was mobile and nontender, and these features were thought to be consistent with a fibroid. The adnexa were difficult to assess because of the enlarged uterus. Point-of-care urine dipstick testing was positive for blood. On measurement of the postvoiding residual urine volume, 270 ml of urine was left in the bladder. Pelvic ultrasonography was performed, and the patient was referred for pelvic-floor physical therapy.

Dr. Aoife Kilcoyne: On a pelvic ultrasound image, the uterus measured 8.5 cm by 8.9 cm by 9.6 cm. A heterogeneous mass (measuring 6.4 cm by 7.8 cm by 8.4 cm) was identified in the uterus. There were multiple small areas of hypoechogenicity in the mass that were most likely consistent with cystic changes or necrosis. The mass had some areas of increased peripheral vascularity. The endometrial echocomplex was not well visualized because of distortion by the mass, but the visualized portion measured 6 mm. The ovaries were not identified, but there were no large adnexal masses.

Dr. Schorge: Seventeen months before this evaluation, the patient presented to her gynecologist for follow-up. She had completed 3 months of pelvic-floor physical therapy and noted that the urinary incontinence had improved slightly. On examination of the pelvis, the mass was reportedly unchanged in size, but the uterus was estimated to be similar in size to the uterus of a pregnant woman at 16 weeks of gestation. Additional imaging studies were performed.

Dr. Kilcoyne: On repeat ultrasonography performed 15 months before this evaluation, the uterus measured 8.9 cm by 9.2 cm by 11.2 cm and had heterogeneous echogenicity. A large fibroid (measuring 7.2 cm by 7.6 cm by 8.0 cm) was present on the left side of the uterus, and it had areas of internal hypoechogenicity that were probably consistent with fluid.

Dr. Schorge: One month later, tenderness in the left lower quadrant developed. After 3 days of symptoms, the patient was evaluated at another hospital, where mild leukocytosis was noted. Computed tomography (CT) of the abdomen and pelvis, performed at the other hospital, reportedly revealed a cystic lesion (measuring 7.1 cm by 7.4 cm by 7.4 cm) in the uterus that was thought to represent cystic degeneration. The size of the mass on CT was similar to previous measurements of the mass on ultrasonography. Follow-up pelvic ultrasonography at 2-month intervals was recommended. At that time, it was thought that in the absence of vaginal bleeding, the pain was probably caused by a degenerating fibroid, and it was recommended that repeat pelvic ultrasonography be performed in 6 weeks.

Dr. Kilcoyne: Pelvic ultrasonography performed 6 weeks later (12 months before this evaluation) revealed a fibroid (measuring 5.6 cm by 6.5 cm by 6.7 cm) on the left side of the uterus that had internal cystic spaces. The fibroid had decreased in overall size since the previous study but had a higher number of cystic components, and it was probably consistent with a large degenerating fibroid.

Figure 1.

Pelvic Ultrasound Images.
Follow-up pelvic ultrasonography performed 4 months later (8 months before this evaluation) revealed a hypoechoic lesion (measuring 5.2 cm by 5.4 cm by 5.8 cm) that probably represented a uterine fibroid. Eight months later (4 days before this evaluation), pelvic ultrasonography was again performed (Figure 1). This examination revealed that the mass had increased in size to 6.9 cm by 8.8 cm by 10.3 cm and again had central cystic components. The endometrial echocomplex was 4 mm, with no pelvic free fluid. Magnetic resonance imaging (MRI) of the pelvis was recommended.

Dr. Schorge: The patient was referred to the gynecologic oncology clinic of this hospital. On evaluation, she reported transient vulvar itching, urinary incontinence, and no constitutional symptoms such as weight loss, constipation, diarrhea, urinary frequency, urinary urgency, or dysuria. She had never had an abnormal Papanicolaou smear. The patient was gravida 3, para 2 (two vaginal deliveries). Her last mammogram had been obtained 8 months earlier and was reportedly normal; she conducted breast self-examinations regularly.

The patient’s medical history included bladder cancer, atrial fibrillation, hyperlipidemia, and hypertension. Medications were warfarin, metoprolol succinate, atorvastatin, fish oil, lorazepam (as needed), and doxepin, as well as calcium, vitamin D, and a multivitamin. Adverse drug reactions included a rash with sulfa drugs. The patient was married and did aerobic exercise three times weekly. She drank wine twice weekly and had never smoked. There was no family history of cancer.

Table 1.

Laboratory Data.
On examination, the patient appeared younger than her stated age. The temperature was 36.7°C, the heart rate 77 beats per minute, and the blood pressure 173/77 mm Hg. The weight was 66.7 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 25.6. The abdomen was soft and nontender. Results of pelvic and rectal examinations were unchanged from the results of recent examinations, and the remainder of the examination was normal. Laboratory test results are shown in Table 1. Additional imaging studies and a diagnostic procedure were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  A 69-year-old woman was evaluated at the gynecologic oncology clinic of this hospital because of persistent urinary incontinence.

Seven years before this evaluation, the patient had received a diagnosis of superficial bladder cancer (low grade), for which a transurethral resection was performed. During the next 5 years, urologic evaluation with annual surveillance cystoscopy revealed no evidence of recurrent disease. Urination occurred frequently and urgently, and tolterodine was administered as needed for symptom control.

Twenty-one months before the current evaluation, the patient was seen by a urogynecologist for persistent urinary incontinence that occurred with bending over, coughing, and sneezing. Urination occurred up to 12 times daily and twice nightly. The patient reported no hematuria, dysuria, incomplete voiding, high fluid intake, pelvic or vaginal pressure or heaviness, prolapse, or fecal incontinence.

On an examination that was limited to the pelvis, the uterus was estimated to be similar in size to the uterus of a pregnant woman at 12 weeks of gestation. The uterus was mobile and nontender, and these features were thought to be consistent with a fibroid. The adnexa were difficult to assess because of the enlarged uterus. Point-of-care urine dipstick testing was positive for blood. On measurement of the postvoiding residual urine volume, 270 ml of urine was left in the bladder. Pelvic ultrasonography was performed, and the patient was referred for pelvic-floor physical therapy.

Dr. Aoife Kilcoyne: On a pelvic ultrasound image, the uterus measured 8.5 cm by 8.9 cm by 9.6 cm. A heterogeneous mass (measuring 6.4 cm by 7.8 cm by 8.4 cm) was identified in the uterus. There were multiple small areas of hypoechogenicity in the mass that were most likely consistent with cystic changes or necrosis. The mass had some areas of increased peripheral vascularity. The endometrial echocomplex was not well visualized because of distortion by the mass, but the visualized portion measured 6 mm. The ovaries were not identified, but there were no large adnexal masses.

Dr. Schorge: Seventeen months before this evaluation, the patient presented to her gynecologist for follow-up. She had completed 3 months of pelvic-floor physical therapy and noted that the urinary incontinence had improved slightly. On examination of the pelvis, the mass was reportedly unchanged in size, but the uterus was estimated to be similar in size to the uterus of a pregnant woman at 16 weeks of gestation. Additional imaging studies were performed.

Dr. Kilcoyne: On repeat ultrasonography performed 15 months before this evaluation, the uterus measured 8.9 cm by 9.2 cm by 11.2 cm and had heterogeneous echogenicity. A large fibroid (measuring 7.2 cm by 7.6 cm by 8.0 cm) was present on the left side of the uterus, and it had areas of internal hypoechogenicity that were probably consistent with fluid.

Dr. Schorge: One month later, tenderness in the left lower quadrant developed. After 3 days of symptoms, the patient was evaluated at another hospital, where mild leukocytosis was noted. Computed tomography (CT) of the abdomen and pelvis, performed at the other hospital, reportedly revealed a cystic lesion (measuring 7.1 cm by 7.4 cm by 7.4 cm) in the uterus that was thought to represent cystic degeneration. The size of the mass on CT was similar to previous measurements of the mass on ultrasonography. Follow-up pelvic ultrasonography at 2-month intervals was recommended. At that time, it was thought that in the absence of vaginal bleeding, the pain was probably caused by a degenerating fibroid, and it was recommended that repeat pelvic ultrasonography be performed in 6 weeks.

Dr. Kilcoyne: Pelvic ultrasonography performed 6 weeks later (12 months before this evaluation) revealed a fibroid (measuring 5.6 cm by 6.5 cm by 6.7 cm) on the left side of the uterus that had internal cystic spaces. The fibroid had decreased in overall size since the previous study but had a higher number of cystic components, and it was probably consistent with a large degenerating fibroid.

Figure 1.

Pelvic Ultrasound Images.
Follow-up pelvic ultrasonography performed 4 months later (8 months before this evaluation) revealed a hypoechoic lesion (measuring 5.2 cm by 5.4 cm by 5.8 cm) that probably represented a uterine fibroid. Eight months later (4 days before this evaluation), pelvic ultrasonography was again performed (Figure 1). This examination revealed that the mass had increased in size to 6.9 cm by 8.8 cm by 10.3 cm and again had central cystic components. The endometrial echocomplex was 4 mm, with no pelvic free fluid. Magnetic resonance imaging (MRI) of the pelvis was recommended.

Dr. Schorge: The patient was referred to the gynecologic oncology clinic of this hospital. On evaluation, she reported transient vulvar itching, urinary incontinence, and no constitutional symptoms such as weight loss, constipation, diarrhea, urinary frequency, urinary urgency, or dysuria. She had never had an abnormal Papanicolaou smear. The patient was gravida 3, para 2 (two vaginal deliveries). Her last mammogram had been obtained 8 months earlier and was reportedly normal; she conducted breast self-examinations regularly.

The patient’s medical history included bladder cancer, atrial fibrillation, hyperlipidemia, and hypertension. Medications were warfarin, metoprolol succinate, atorvastatin, fish oil, lorazepam (as needed), and doxepin, as well as calcium, vitamin D, and a multivitamin. Adverse drug reactions included a rash with sulfa drugs. The patient was married and did aerobic exercise three times weekly. She drank wine twice weekly and had never smoked. There was no family history of cancer.

Table 1.

Laboratory Data.
On examination, the patient appeared younger than her stated age. The temperature was 36.7°C, the heart rate 77 beats per minute, and the blood pressure 173/77 mm Hg. The weight was 66.7 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 25.6. The abdomen was soft and nontender. Results of pelvic and rectal examinations were unchanged from the results of recent examinations, and the remainder of the examination was normal. Laboratory test results are shown in Table 1. Additional imaging studies and a diagnostic procedure were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Leiomyosarcoma of the uterus. The patient has a history of a uterine mass that was initially thought to be a fibroid. However, the mass has been increasing in size and has developed cystic components, which is not typical for a fibroid. The patient also has a history of bladder cancer, which could increase her risk for other types of cancer. The mass was also described as heterogeneous, which could suggest malignancy. The patient's symptoms of urinary incontinence could be due to the mass pressing on the bladder.""
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        ""content"": ""The patient is a 69-year-old woman with a history of bladder cancer and a persistent urinary incontinence. She has a mass in her uterus that has been monitored for several years and has recently increased in size. The mass was initially thought to be a fibroid, but its recent growth and the patient's history of cancer raise the possibility of a malignant tumor. The differential diagnosis includes uterine fibroids, endometrial cancer, and recurrent bladder cancer. The patient's urinary symptoms could be due to the mass pressing on the bladder, or they could be a sign of recurrent bladder cancer. However, the patient has no hematuria, which would be expected in bladder cancer. Endometrial cancer is a possibility given the patient's age and the presence of a uterine mass, but the patient has no abnormal vaginal bleeding, which is a common symptom of endometrial cancer. The mass was initially thought to be a fibroid, and its recent growth could be due to degeneration, which can cause fibroids to rapidly increase in size. However, the rapid growth of the mass and the patient's history of cancer make a malignant tumor a possibility that needs to be ruled out.\n\nDiagnosis: Malignant uterine tumor.""
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10.1056/NEJMcpc1616396,"Case 15-2017 — A 27-Year-Old Woman with Anemia, Thrombocytosis, and Skin Lesions after Travel Abroad",,Takayasu’s arteritis.,Takayasu’s arteritis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:             A 27-year-old woman was evaluated in the infectious disease clinic of this hospital because of skin lesions, anemia, thrombocytosis, and an elevated blood alkaline phosphatase level.

Eleven months before this presentation, the patient traveled abroad; she lived for 2 months in Morocco and then for 2 months in Thailand, and during that time, she also traveled briefly to South Korea. She returned to New England and was well until 5 months before this presentation, when a painful erythematous papule developed on her chin. During the next week, she felt feverish. More papules developed near the initial skin lesion and coalesced into a plaque. A similar, larger skin lesion developed on the right forearm, and a small amount of white fluid drained from it. The patient presented to her primary care physician at another hospital for evaluation.

At the primary care clinic, the patient reported myalgias and occasional sore throat. On examination, the temperature was 36.8°C and the blood pressure 110/60 mm Hg. A 1-cm erythematous plaque with no ulceration was present on the left side of the chin, and a 1.5-cm lesion that was similar in appearance was present on the right forearm. Cephalexin was prescribed.

Table 1.

Laboratory Data.
Three days later, the skin lesions had not improved, and a new lesion had developed on the left forearm. The patient returned to the primary care clinic. On examination, the lesion on the right forearm was fluctuant. Incision yielded a small amount of bloody fluid; a culture of this fluid had no growth. A blood culture was also negative. Blood levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, total protein, and albumin were normal; other laboratory test results are shown in Table 1. Abdominal ultrasonography revealed increased echogenicity of the hepatic parenchyma (a finding suggestive of fatty infiltration) with no focal lesions of the liver. The gallbladder was normal, with no gallstones, and there was no dilatation of the intrahepatic or extrahepatic bile duct. Trimethoprim–sulfamethoxazole and topical mupirocin were prescribed, and the patient was referred to a gastroenterologist because of the elevated blood alkaline phosphatase level.

In the gastroenterology clinic, the patient reported intermittent fatigue but no pruritus, abdominal pain, or arthralgias. Tests for antimitochondrial antibodies and antinuclear antibodies were negative. Results of magnetic resonance cholangiopancreatography confirmed that the gallbladder, intrahepatic and extrahepatic biliary systems, and size and contour of the liver were normal. The elevated blood alkaline phosphatase level was thought to be related to nonalcoholic fatty liver disease; weight loss was advised.

The patient returned to the primary care clinic for follow-up after completing the 7-day course of trimethoprim–sulfamethoxazole and topical mupirocin for treatment of the skin lesions. She reported that the lesions had decreased in size but continued to be painful. On examination, the lesion on the left forearm had resolved, and the lesion on the left side of the chin had decreased in size, flattened in appearance, and faded. The lesion on the right forearm remained erythematous and raised, with an overlying serous crust. The patient was referred to a dermatologist for further evaluation.

On examination in the dermatology clinic, there were well-demarcated, atrophic, depressed plaques on the left side of the chin. The appearance of the lesion on the right forearm was unchanged, and Gram’s staining and culture of that lesion were negative. Cephalexin and topical clobetasol were prescribed.

During the next week, the lesion on the chin recurred, and the patient returned to the primary care clinic. On examination, a 2-cm circular, erythematous plaque was present at the site of the previous chin lesion, and the lesion on the right forearm had increased in size to 2 cm in diameter. A shave biopsy of the lesion on the chin was performed. Histologic examination reportedly revealed a perifollicular granulomatous and mixed inflammatory infiltrate that included neutrophils and eosinophils. No organisms were seen on periodic acid–Schiff staining, Gram’s staining, or staining for acid-fast bacilli. Doxycycline was prescribed.

The patient traveled to Jordan and stayed for 4 weeks; during that time, the lesion on the left side of the chin receded, the lesion on the right forearm doubled in size, and the lesion on the left forearm recurred. Clusters of painful vulvovaginal ulcers developed; these waxed and waned. On her return to New England, the patient was referred by her primary care physician to an infectious disease specialist at this hospital.

In the infectious disease clinic, the patient reported a 5-month history of waxing and waning skin lesions, a 2-month history of episodic vulvovaginal ulcers, and occasional nausea. She had a history of attention-deficit disorder. She took a combination birth control pill daily. Her father had diabetes mellitus, and her mother had hypertension and polymyalgia rheumatica. The patient was of European descent. She was a graduate student and traveled abroad frequently for internships. While she was in Morocco 11 months earlier, she rode on a camel; while she was in Thailand, she petted an elephant and swam in freshwater waterfall pools. She had not visited farms or milked animals and had no known sick contacts. She had been sexually active for several years with one partner, who used condoms.

On examination, the temperature was 36.5°C, the blood pressure 90/52 mm Hg, the pulse 66 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.9. On the left side of the chin, there was a 2-cm area of faded erythema with a depressed, atrophic plaque. On each forearm, there was a 5-cm, well-demarcated, depressed, atrophic plaque with no ulceration or crust. Two 2-mm ulcers were present on the right labium minus and vaginal fourchette. The remainder of the examination was normal. An interferon-_ release assay for Mycobacterium tuberculosis was negative, as were tests for hepatitis B virus surface antigen, hepatitis B virus core IgM antibodies, human immunodeficiency virus (HIV) type 1 p24 antigen, and HIV type 1 and type 2 antibodies. Blood levels of electrolytes and glucose and results of renal-function tests were normal; other laboratory test results are shown in Table 1. The biopsy specimen from the left side of the chin that had been obtained 4 months earlier was reviewed at this hospital.

Figure 1.

Skin-Biopsy Specimen from the Left Side of the Chin.
Dr. Ruth K. Foreman: Histologic examination of the shave-biopsy specimen revealed a granulomatous dermal infiltrate (Figure 1A) that was composed of macrophages and scattered giant cells arranged in loose clusters. Admixed neutrophils and eosinophils were also seen (Figure 1B). No microorganisms were identified on Gram’s staining, periodic acid–Schiff staining, staining for acid-fast bacilli, or Giemsa staining. These histologic features are consistent with the diagnosis of granulomatous dermatitis, an entity that has numerous infectious and noninfectious causes. In this case, the shave-biopsy specimen consisted of only superficial dermis, and many of the features necessary for definitive pathological diagnosis were not present in the specimen. Given the presence of neutrophils, infection should be ruled out before noninfectious causes are considered.

Table 2.

Microbiologic Data.
Dr. Letourneau: Additional laboratory tests were performed; the results are shown in Table 2. Computed tomography (CT) of the chest, abdomen, and pelvis was ordered.

Four weeks after the patient was evaluated in the infectious disease clinic of this hospital, fatigue and weakness developed in the left arm, along with associated numbness and tingling. The patient was evaluated in a clinic at this hospital, and the blood pressure could not be obtained in either arm despite multiple attempts at manual sphygmomanometry. The radial pulses were not palpable, but the hands were warm and had no changes in skin color.

A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  A 27-year-old woman was evaluated in the infectious disease clinic of this hospital because of skin lesions, anemia, thrombocytosis, and an elevated blood alkaline phosphatase level.

Eleven months before this presentation, the patient traveled abroad; she lived for 2 months in Morocco and then for 2 months in Thailand, and during that time, she also traveled briefly to South Korea. She returned to New England and was well until 5 months before this presentation, when a painful erythematous papule developed on her chin. During the next week, she felt feverish. More papules developed near the initial skin lesion and coalesced into a plaque. A similar, larger skin lesion developed on the right forearm, and a small amount of white fluid drained from it. The patient presented to her primary care physician at another hospital for evaluation.

At the primary care clinic, the patient reported myalgias and occasional sore throat. On examination, the temperature was 36.8°C and the blood pressure 110/60 mm Hg. A 1-cm erythematous plaque with no ulceration was present on the left side of the chin, and a 1.5-cm lesion that was similar in appearance was present on the right forearm. Cephalexin was prescribed.

Table 1.

Laboratory Data.
Three days later, the skin lesions had not improved, and a new lesion had developed on the left forearm. The patient returned to the primary care clinic. On examination, the lesion on the right forearm was fluctuant. Incision yielded a small amount of bloody fluid; a culture of this fluid had no growth. A blood culture was also negative. Blood levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, total protein, and albumin were normal; other laboratory test results are shown in Table 1. Abdominal ultrasonography revealed increased echogenicity of the hepatic parenchyma (a finding suggestive of fatty infiltration) with no focal lesions of the liver. The gallbladder was normal, with no gallstones, and there was no dilatation of the intrahepatic or extrahepatic bile duct. Trimethoprim–sulfamethoxazole and topical mupirocin were prescribed, and the patient was referred to a gastroenterologist because of the elevated blood alkaline phosphatase level.

In the gastroenterology clinic, the patient reported intermittent fatigue but no pruritus, abdominal pain, or arthralgias. Tests for antimitochondrial antibodies and antinuclear antibodies were negative. Results of magnetic resonance cholangiopancreatography confirmed that the gallbladder, intrahepatic and extrahepatic biliary systems, and size and contour of the liver were normal. The elevated blood alkaline phosphatase level was thought to be related to nonalcoholic fatty liver disease; weight loss was advised.

The patient returned to the primary care clinic for follow-up after completing the 7-day course of trimethoprim–sulfamethoxazole and topical mupirocin for treatment of the skin lesions. She reported that the lesions had decreased in size but continued to be painful. On examination, the lesion on the left forearm had resolved, and the lesion on the left side of the chin had decreased in size, flattened in appearance, and faded. The lesion on the right forearm remained erythematous and raised, with an overlying serous crust. The patient was referred to a dermatologist for further evaluation.

On examination in the dermatology clinic, there were well-demarcated, atrophic, depressed plaques on the left side of the chin. The appearance of the lesion on the right forearm was unchanged, and Gram’s staining and culture of that lesion were negative. Cephalexin and topical clobetasol were prescribed.

During the next week, the lesion on the chin recurred, and the patient returned to the primary care clinic. On examination, a 2-cm circular, erythematous plaque was present at the site of the previous chin lesion, and the lesion on the right forearm had increased in size to 2 cm in diameter. A shave biopsy of the lesion on the chin was performed. Histologic examination reportedly revealed a perifollicular granulomatous and mixed inflammatory infiltrate that included neutrophils and eosinophils. No organisms were seen on periodic acid–Schiff staining, Gram’s staining, or staining for acid-fast bacilli. Doxycycline was prescribed.

The patient traveled to Jordan and stayed for 4 weeks; during that time, the lesion on the left side of the chin receded, the lesion on the right forearm doubled in size, and the lesion on the left forearm recurred. Clusters of painful vulvovaginal ulcers developed; these waxed and waned. On her return to New England, the patient was referred by her primary care physician to an infectious disease specialist at this hospital.

In the infectious disease clinic, the patient reported a 5-month history of waxing and waning skin lesions, a 2-month history of episodic vulvovaginal ulcers, and occasional nausea. She had a history of attention-deficit disorder. She took a combination birth control pill daily. Her father had diabetes mellitus, and her mother had hypertension and polymyalgia rheumatica. The patient was of European descent. She was a graduate student and traveled abroad frequently for internships. While she was in Morocco 11 months earlier, she rode on a camel; while she was in Thailand, she petted an elephant and swam in freshwater waterfall pools. She had not visited farms or milked animals and had no known sick contacts. She had been sexually active for several years with one partner, who used condoms.

On examination, the temperature was 36.5°C, the blood pressure 90/52 mm Hg, the pulse 66 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 24.9. On the left side of the chin, there was a 2-cm area of faded erythema with a depressed, atrophic plaque. On each forearm, there was a 5-cm, well-demarcated, depressed, atrophic plaque with no ulceration or crust. Two 2-mm ulcers were present on the right labium minus and vaginal fourchette. The remainder of the examination was normal. An interferon-_ release assay for Mycobacterium tuberculosis was negative, as were tests for hepatitis B virus surface antigen, hepatitis B virus core IgM antibodies, human immunodeficiency virus (HIV) type 1 p24 antigen, and HIV type 1 and type 2 antibodies. Blood levels of electrolytes and glucose and results of renal-function tests were normal; other laboratory test results are shown in Table 1. The biopsy specimen from the left side of the chin that had been obtained 4 months earlier was reviewed at this hospital.

Figure 1.

Skin-Biopsy Specimen from the Left Side of the Chin.
Dr. Ruth K. Foreman: Histologic examination of the shave-biopsy specimen revealed a granulomatous dermal infiltrate (Figure 1A) that was composed of macrophages and scattered giant cells arranged in loose clusters. Admixed neutrophils and eosinophils were also seen (Figure 1B). No microorganisms were identified on Gram’s staining, periodic acid–Schiff staining, staining for acid-fast bacilli, or Giemsa staining. These histologic features are consistent with the diagnosis of granulomatous dermatitis, an entity that has numerous infectious and noninfectious causes. In this case, the shave-biopsy specimen consisted of only superficial dermis, and many of the features necessary for definitive pathological diagnosis were not present in the specimen. Given the presence of neutrophils, infection should be ruled out before noninfectious causes are considered.

Table 2.

Microbiologic Data.
Dr. Letourneau: Additional laboratory tests were performed; the results are shown in Table 2. Computed tomography (CT) of the chest, abdomen, and pelvis was ordered.

Four weeks after the patient was evaluated in the infectious disease clinic of this hospital, fatigue and weakness developed in the left arm, along with associated numbness and tingling. The patient was evaluated in a clinic at this hospital, and the blood pressure could not be obtained in either arm despite multiple attempts at manual sphygmomanometry. The radial pulses were not palpable, but the hands were warm and had no changes in skin color.

A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Takayasu's arteritis. The patient's symptoms of skin lesions, anemia, thrombocytosis, and elevated blood alkaline phosphatase level, along with her recent travel history, initially suggest an infectious disease. However, the lack of response to antibiotics and negative cultures rule out a bacterial infection. The presence of granulomas in the skin biopsy could suggest a granulomatous disease such as sarcoidosis, but the patient's symptoms do not fully align with this diagnosis. The development of fatigue, weakness, numbness, and tingling in the left arm, along with the inability to obtain a blood pressure reading or palpate the radial pulses, suggest a vascular issue. These symptoms, along with the patient's age and gender, are consistent with Takayasu's arteritis, a rare type of vasculitis that causes inflammation in the large arteries.""
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        ""content"": ""The patient's symptoms include skin lesions, anemia, thrombocytosis, and an elevated blood alkaline phosphatase level. She has a history of travel to Morocco, Thailand, and South Korea. The skin lesions are described as erythematous papules that coalesce into plaques, and they have not responded to antibiotics. The patient also has a history of vulvovaginal ulcers. The skin biopsy revealed a granulomatous dermal infiltrate, which can be caused by numerous infectious and noninfectious causes. Given the patient's travel history and the presence of granulomas, an infectious cause is likely. The patient's symptoms and biopsy results are consistent with cutaneous leishmaniasis, a parasitic disease transmitted by the bite of a sandfly. This disease is endemic in many parts of the world, including Morocco and Thailand.\n\nDiagnosis: Cutaneous Leishmaniasis.""
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        ""content"": ""The patient is a 27-year-old woman with a history of travel to Morocco, Thailand, and South Korea, presenting with skin lesions, anemia, thrombocytosis, and elevated blood alkaline phosphatase level. The differential diagnosis for this patient includes infectious diseases such as leishmaniasis, tuberculosis, or other mycobacterial infections, given her travel history and the granulomatous dermatitis seen on biopsy. Non-infectious causes such as sarcoidosis or autoimmune diseases could also be considered. However, the patient's history of travel to endemic areas, the presence of skin lesions, and the granulomatous inflammation seen on biopsy make leishmaniasis a strong possibility. The patient's symptoms do not improve with antibiotics, which would be expected if the cause was a bacterial infection. The patient also has a negative interferon-gamma release assay, which makes tuberculosis less likely. The patient does not have systemic symptoms such as fever, weight loss, or night sweats that would be expected with sarcoidosis or autoimmune diseases. The patient's anemia and thrombocytosis could be explained by a chronic inflammatory state due to an ongoing infection. The elevated alkaline phosphatase could be due to liver involvement by the disease. \n\nDiagnosis: Cutaneous leishmaniasis.""
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10.1056/NEJMcpc1616397,Case 14-2017 — A 20-Year-Old Man with Pain and Swelling of the Left Calf and a Purpuric Rash,,IgA vasculitis.,IgA vasculitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:           A 20-year-old man was seen in an outpatient clinic of this hospital because of pain and swelling of the left calf and a purpuric rash.

Figure 1.

Clinical Photograph of the Nares.
The patient had been well until 3 weeks before presentation to this hospital, when sore throat, nonproductive cough, rhinorrhea, and chills developed. He noted areas of crusting and occasional bleeding in both nares (Figure 1). His brother had reportedly received a recent diagnosis of streptococcal pharyngitis.

Two weeks before presentation to this hospital, the patient had traveled by airplane to the northwestern United States for a wilderness backpacking trip. Shortly after he arrived, cramping pain developed in his left calf. Over the next 2 days, the pain worsened in severity and was associated with swelling of the calf. He presented to another clinic for evaluation. Noninvasive ultrasonography of the lower leg was performed, and the results were reportedly normal. Ibuprofen was recommended for pain control, and azithromycin was prescribed for suspected upper respiratory infection. Despite the administration of ibuprofen, the pain in the left calf worsened and limited the patient’s ability to bear weight. The swelling progressed from the calf to the foot, and an erythematous rash developed on the dorsum of both feet.

One week before presentation to this hospital, the patient was evaluated in the emergency department of another hospital. He had a history of Crohn’s disease, which had been diagnosed when he was 10 years of age and had resulted in prolonged glucocorticoid use. During the previous 3 years, weekly treatment with adalimumab led to clinical improvement in his Crohn’s disease and he had a considerable growth spurt, in which he gained several inches in height. During the previous several years, the patient had had multiple self-limited episodes of sore throat, nonproductive cough, rhinorrhea, and nasal crusting with associated bleeding. He occasionally used ibuprofen at home but took no other over-the-counter or herbal medications. He was a college student and resided in the central United States. He drank alcohol occasionally and did not smoke tobacco or use illicit drugs. He had a sibling with Crohn’s disease.

Figure 2.

Clinical Photographs of the Lower Legs.
On examination at the other hospital, the temperature was 36.2°C, the blood pressure 118/70 mm Hg, the pulse 70 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. He did not appear ill but was in mild distress because of the pain in the left lower leg. The nasal crusting and the swelling of nasal mucous membranes had markedly improved during the previous 2 weeks. The nasal septum was intact, and no nasal polyps or blood were present. Examination of the neck, heart, lungs, and abdomen was normal. There was tenderness on palpation and swelling in the left lower leg from the calf to the dorsal aspect of the foot, without erythema, warmth, or pitting (Figure 2A). Synovitis of the left ankle was present. Peripheral pulses were normal. Nontender purpuric lesions, including some that were faintly palpable, were present on both lower legs but were more numerous on the left leg (Figure 2B). Two tender nodules (each 1 cm in diameter) with overlying erythema were present above the right medial malleolus (Figure 2C) and were similar to lesions the patient had had transiently in the past. Blood levels of electrolytes, glucose, creatine kinase, C3, and C4 were normal, as were results of renal- and liver-function tests, the complete blood count, and the differential count. Assays for antinuclear antibodies and antineutrophil cytoplasmic antibodies (ANCAs) were negative. Tests for hepatitis B virus surface antigen, hepatitis B virus surface antibodies, hepatitis C virus antibodies, human immunodeficiency virus (HIV) type 1 p24 antigen, and HIV type 1 and type 2 antibodies were negative. Blood cultures showed no growth. Urinalysis revealed clear, yellow urine, with a specific gravity of 1.014 and a pH of 5.5 and with no glucose, ketones, bilirubin, protein, blood, or nitrates by dipstick; examination of the sediment revealed no red cells, white cells, bacteria, or casts. The blood C-reactive protein level was 2.0 mg per deciliter (reference range, 0 to 0.9), the erythrocyte sedimentation rate 30 mm per hour (reference range, <10), and an antistreptolysin O titer 400 IU per milliliter (reference range, 0 to 200).

Radiography of the chest revealed a normal cardiac silhouette and no consolidations or pleural effusions. Computed tomography of the tibia, fibula, and foot, performed after the administration of intravenous contrast material, revealed normal osseous structures without fractures or cortical erosions, as well as diffuse nonspecific edema of the soft tissues of the ankle and proximal dorsal foot without abscesses or deep fascial thickening.

The patient was admitted to the other hospital, and diagnostic tests were performed. He then traveled to New England to visit family and was referred to this hospital for further treatment.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                       A 20-year-old man was seen in an outpatient clinic of this hospital because of pain and swelling of the left calf and a purpuric rash.

Figure 1.

Clinical Photograph of the Nares.
The patient had been well until 3 weeks before presentation to this hospital, when sore throat, nonproductive cough, rhinorrhea, and chills developed. He noted areas of crusting and occasional bleeding in both nares (Figure 1). His brother had reportedly received a recent diagnosis of streptococcal pharyngitis.

Two weeks before presentation to this hospital, the patient had traveled by airplane to the northwestern United States for a wilderness backpacking trip. Shortly after he arrived, cramping pain developed in his left calf. Over the next 2 days, the pain worsened in severity and was associated with swelling of the calf. He presented to another clinic for evaluation. Noninvasive ultrasonography of the lower leg was performed, and the results were reportedly normal. Ibuprofen was recommended for pain control, and azithromycin was prescribed for suspected upper respiratory infection. Despite the administration of ibuprofen, the pain in the left calf worsened and limited the patient’s ability to bear weight. The swelling progressed from the calf to the foot, and an erythematous rash developed on the dorsum of both feet.

One week before presentation to this hospital, the patient was evaluated in the emergency department of another hospital. He had a history of Crohn’s disease, which had been diagnosed when he was 10 years of age and had resulted in prolonged glucocorticoid use. During the previous 3 years, weekly treatment with adalimumab led to clinical improvement in his Crohn’s disease and he had a considerable growth spurt, in which he gained several inches in height. During the previous several years, the patient had had multiple self-limited episodes of sore throat, nonproductive cough, rhinorrhea, and nasal crusting with associated bleeding. He occasionally used ibuprofen at home but took no other over-the-counter or herbal medications. He was a college student and resided in the central United States. He drank alcohol occasionally and did not smoke tobacco or use illicit drugs. He had a sibling with Crohn’s disease.

Figure 2.

Clinical Photographs of the Lower Legs.
On examination at the other hospital, the temperature was 36.2°C, the blood pressure 118/70 mm Hg, the pulse 70 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. He did not appear ill but was in mild distress because of the pain in the left lower leg. The nasal crusting and the swelling of nasal mucous membranes had markedly improved during the previous 2 weeks. The nasal septum was intact, and no nasal polyps or blood were present. Examination of the neck, heart, lungs, and abdomen was normal. There was tenderness on palpation and swelling in the left lower leg from the calf to the dorsal aspect of the foot, without erythema, warmth, or pitting (Figure 2A). Synovitis of the left ankle was present. Peripheral pulses were normal. Nontender purpuric lesions, including some that were faintly palpable, were present on both lower legs but were more numerous on the left leg (Figure 2B). Two tender nodules (each 1 cm in diameter) with overlying erythema were present above the right medial malleolus (Figure 2C) and were similar to lesions the patient had had transiently in the past. Blood levels of electrolytes, glucose, creatine kinase, C3, and C4 were normal, as were results of renal- and liver-function tests, the complete blood count, and the differential count. Assays for antinuclear antibodies and antineutrophil cytoplasmic antibodies (ANCAs) were negative. Tests for hepatitis B virus surface antigen, hepatitis B virus surface antibodies, hepatitis C virus antibodies, human immunodeficiency virus (HIV) type 1 p24 antigen, and HIV type 1 and type 2 antibodies were negative. Blood cultures showed no growth. Urinalysis revealed clear, yellow urine, with a specific gravity of 1.014 and a pH of 5.5 and with no glucose, ketones, bilirubin, protein, blood, or nitrates by dipstick; examination of the sediment revealed no red cells, white cells, bacteria, or casts. The blood C-reactive protein level was 2.0 mg per deciliter (reference range, 0 to 0.9), the erythrocyte sedimentation rate 30 mm per hour (reference range, <10), and an antistreptolysin O titer 400 IU per milliliter (reference range, 0 to 200).

Radiography of the chest revealed a normal cardiac silhouette and no consolidations or pleural effusions. Computed tomography of the tibia, fibula, and foot, performed after the administration of intravenous contrast material, revealed normal osseous structures without fractures or cortical erosions, as well as diffuse nonspecific edema of the soft tissues of the ankle and proximal dorsal foot without abscesses or deep fascial thickening.

The patient was admitted to the other hospital, and diagnostic tests were performed. He then traveled to New England to visit family and was referred to this hospital for further treatment.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This 20-year-old male patient with a history of Crohn’s disease presents with calf pain and swelling, a purpuric rash, and nasal symptoms such as crusting and bleeding.

Step 1: Firstly, his nasal crusting and bleeding, a common symptom of Wegener's granulomatosis (now known as granulomatosis with polyangiitis, or GPA), was improved and ANCA test, specific for GPA, was negative, which makes GPA less likely.

Step 2: He has a history of Crohn's disease, an inflammatory bowel disease that can be associated with systemic inflammation and extra-intestinal symptoms. This history raises suspicion for an autoimmune or vasculitic process.

Step 3: He has elevated antistreptolysin O (ASO) titer, which indicates a recent streptococcal infection. High ASO titers are usually associated with post-streptococcal complications like acute rheumatic fever or post-streptococcal glomerulonephritis, but these typically don't cause purpura or calf pain.

Step 4: His lower leg symptoms, which include pain, swelling, and purpuric lesions, are suggestive of a vasculitic process. Vasculitides such as Henoch-Schonlein purpura (HSP) could cause these symptoms, but HSP is more common in children and usually involves the kidneys, which isn't apparent in this case. The absence of red cells, white cells, bacteria, or casts in urine sediment speaks against HSP or any vasculitis with renal involvement.

Step 5: Painful calf swelling and purpura could be seen in disorders like deep vein thrombosis (DVT), but an ultrasound of the lower leg was normal, ruling out DVT.

Step 6: He has synovitis of the ankle, suggestive of an inflammatory arthritis. The most relevant rheumatologic conditions here would be the spondyloarthropathies, such as ankylosing spondylitis, which can be associated with inflammatory bowel disease. However, these conditions usually don't cause purpura.

Step 7: His use of adalimumab, a TNF-alpha inhibitor used for conditions like Crohn's disease, is important. Adalimumab can induce a form of vasculitis, and in some cases, it can cause a condition known as leukocytoclastic vasculitis. This condition often presents with a purpuric rash on the lower extremities, as well as symptoms like fever and arthralgia.

Therefore, it seems that the patient's combination of symptoms can be best explained by adalimumab-induced leukocytoclastic vasculitis.

Diagnosis: Adalimumab-induced leukocytoclastic vasculitis.","{
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        ""content"": ""Granulomatosis with polyangiitis (GPA). The patient's history of Crohn's disease and prolonged glucocorticoid use, along with his symptoms of sore throat, nonproductive cough, rhinorrhea, and nasal crusting with associated bleeding, suggest an autoimmune condition. The negative tests for antinuclear antibodies and antineutrophil cytoplasmic antibodies (ANCAs) do not rule out GPA, as these tests can be negative in limited or early disease. The patient's leg pain, swelling, and purpuric rash are consistent with vasculitis, a key feature of GPA. The elevated C-reactive protein level and erythrocyte sedimentation rate further suggest an inflammatory process.""
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        ""content"": ""The patient is a 20-year-old male with a history of Crohn's disease, presenting with pain and swelling in the left calf, a purpuric rash, and a recent history of upper respiratory symptoms. The differential diagnosis for this patient includes deep vein thrombosis (DVT), cellulitis, vasculitis, and septic arthritis. The normal results of the noninvasive ultrasonography of the lower leg make DVT less likely. The absence of erythema and warmth in the affected area makes cellulitis less likely. The patient's history of Crohn's disease, a chronic inflammatory condition, and the presence of a purpuric rash and synovitis of the left ankle suggest an inflammatory or autoimmune process, such as vasculitis. The negative ANCA test makes certain types of vasculitis, such as granulomatosis with polyangiitis, less likely. However, the patient's history of multiple self-limited episodes of sore throat, nonproductive cough, rhinorrhea, and nasal crusting with associated bleeding, along with the elevated antistreptolysin O titer, suggest a recent streptococcal infection, which can trigger a type of vasculitis known as Henoch-Sch\u00f6nlein purpura (HSP). HSP typically presents with a purpuric rash, joint pain, and gastrointestinal symptoms, which can be seen in patients with Crohn's disease. \n\nDiagnosis: Henoch-Sch\u00f6nlein purpura.""
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10.1056/NEJMcpc1616022,"Case 13-2017 — A 41-Year-Old Man with Hearing Loss, Seizures, Weakness, and Cognitive Decline",,"MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes).","MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes).","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:             A 41-year-old man was seen in the neurology clinic of this hospital because of seizures, weakness, and cognitive decline.

The patient had a history of migraine headaches, sensorineural hearing loss, and chronic proteinuria. He had been in his usual health until approximately 2 years before presentation to this hospital, when his wife noted subtle changes in his personality and behavior, including short-tempered and argumentative reactions that “didn’t make sense.” One year before presentation to this hospital, headache, malaise, and fatigue occurred for approximately 1 week, followed by the sudden onset of difficulty speaking; over a period of several hours, he progressed from being able to use well-formed but incorrect words to being completely unable to speak and partially unable to write. Later that day, he was admitted to another hospital.

Figure 1.

MRI Studies of the Brain Obtained before Presentation.
Dr. William A. Copen: Magnetic resonance imaging (MRI) of the brain was performed 1 year, 10 months, and 7 months before the patient’s presentation to this hospital (Figure 1). All the studies revealed global brain parenchymal volume loss that was far more advanced than would be expected for a patient of this age. On the first study (Figure 1A), T2-weighted images showed a mildly expansile, hyperintense intraaxial lesion that was centered in the anterior left temporal lobe and extended posteriorly and superiorly into the inferior parietal lobule. This lesion disproportionately involved the subcortical white matter, although the cortex was also affected. There was no evidence of associated restricted diffusion or magnetic susceptibility effect and no abnormal enhancement on contrast-enhanced images. On the two subsequent studies (Figure 1B and 1C), the lesion maintained similar signal characteristics but decreased in size; in fact, the third study revealed that the lesion had resolved almost completely. The results of magnetic resonance angiography and venography were normal.

Table 1.

Laboratory Data.
Dr. Reda: On the patient’s admission to the other hospital, 1 year before presentation to this hospital, laboratory testing revealed mild anemia, with a mean corpuscular volume of 65 fl (reference range, 79 to 92); other test results, including the results of cerebrospinal fluid analysis, are shown in Table 1. A diagnosis of stroke was made, and therapy with aspirin and a lipid-lowering agent was begun. The patient was discharged home. His language abilities gradually improved over the next 2 months but did not return to baseline, and his headaches persisted.

One month after discharge, while the patient was at home, he had a generalized tonic–clonic seizure that was witnessed by his wife. Therapy with levetiracetam was begun, and no further seizure activity occurred. During the next 11 months, he had fluctuating focal neurologic symptoms, rapidly progressive cognitive decline, weakness, and gait instability, along with nearly daily diffuse headaches, muscle cramps in his calves, and weight loss of 11 kg.

One month before the patient’s presentation to this hospital, blood levels of cholesterol and lipids and results of liver- and renal-function tests were normal; other test results are shown in Table 1. During the 2 weeks before presentation, the patient’s wife noted that his behavior had become more childlike, with rambling speech, impulsivity, and anger. His gait, balance, and coordination worsened, although he did not fall, and swallowing difficulties developed. He was referred to the neurology clinic at this hospital.

The patient was right-handed. He had congenital short stature. When he was 25 years of age, sensorineural hearing loss (worse on the right side than on the left) developed; it gradually worsened and led to the use of hearing aids. Proteinuria was noted when he was 25 years of age. In the past, a clinical diagnosis of gout had been made after an episode of swelling and pain in the left big toe. Medications were levetiracetam, lisinopril, and a multivitamin. He had no known allergies. He was married, had a young child, and had lived in the southwestern United States until 3 weeks before this presentation, when his family moved to be near relatives in New England. He was a lawyer but had been receiving disability benefits since the onset of this illness. He drank alcohol in moderation and smoked tobacco occasionally. His mother was of French Canadian and Irish descent; she had reportedly had lupus nephritis with antinuclear antibodies, diabetes mellitus, and colitis and was described as needing rest frequently when walking. His father was of Hungarian and Italian descent and had diabetes mellitus and coronary artery disease. A maternal aunt and uncle had diabetes mellitus, and the same uncle also had sensorineural hearing loss. He had nine siblings who ranged in height from 150 to 163 cm; some were reportedly well and others had mild gastrointestinal dysmotility or symptoms of the irritable bowel syndrome, sensorineural hearing loss, anxiety, and _-thalassemia trait.

On examination, the patient appeared cachectic. The blood pressure was 112/72 mm Hg, the pulse 83 beats per minute, the temperature 36.8°C, and the oxygen saturation 99% while he was breathing ambient air. His weight was 40.5 kg, and his height 152 cm. During the examination, he reached out to grab the examiner’s hand and glasses inappropriately. The Montreal Cognitive Assessment score was 25 on a scale ranging from 0 to 30 (with higher scores indicating better cognitive function); points were deducted because the patient made errors of visuospatial function, repetition, and fluency and incorrectly identified a glove as a hand and a feather as a leaf. He had ataxic dysarthria with telegraphic speech and frequent tangential ramblings that were difficult to interrupt. The optic disks were flat and without pallor. The visual fields were normal on confrontation testing. The pupils were round, equal, and reactive, without Horner’s syndrome or a relative afferent pupillary defect. Upward gaze was markedly restricted, lateral gaze moderately restricted, and downward gaze mildly restricted in each eye. There was mild bifacial weakness and markedly impaired hearing bilaterally, even while the patient was wearing hearing aids. There was minimal weakness of shoulder abduction bilaterally. The muscle bulk, tone, and strength of the neck and limbs were otherwise normal, without tremor, other adventitious movements, or fasciculations. Finger–nose–finger and heel–knee–shin testing revealed subtle dysmetria; rapid alternating movements were slightly irregular. No truncal ataxia was present while the patient was seated. He swayed prominently while he stood with his feet together and eyes closed. His gait was mildly ataxic, and he could not take more than two tandem steps without losing his balance. The remainder of the neurologic and general examinations was normal.

Laboratory testing revealed a mild secondary carnitine deficiency, which was thought to be dietary. The lactic acid level was initially normal but subsequently increased and remained elevated; the highest level was 8.3 mmol per liter (75 mg per deciliter; reference range, 0.5 to 2.2 mmol per liter [5 to 20 mg per deciliter]). Other test results are shown in Table 1.

Diagnostic procedures were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:               A 41-year-old man was seen in the neurology clinic of this hospital because of seizures, weakness, and cognitive decline.

The patient had a history of migraine headaches, sensorineural hearing loss, and chronic proteinuria. He had been in his usual health until approximately 2 years before presentation to this hospital, when his wife noted subtle changes in his personality and behavior, including short-tempered and argumentative reactions that “didn’t make sense.” One year before presentation to this hospital, headache, malaise, and fatigue occurred for approximately 1 week, followed by the sudden onset of difficulty speaking; over a period of several hours, he progressed from being able to use well-formed but incorrect words to being completely unable to speak and partially unable to write. Later that day, he was admitted to another hospital.

Figure 1.

MRI Studies of the Brain Obtained before Presentation.
Dr. William A. Copen: Magnetic resonance imaging (MRI) of the brain was performed 1 year, 10 months, and 7 months before the patient’s presentation to this hospital (Figure 1). All the studies revealed global brain parenchymal volume loss that was far more advanced than would be expected for a patient of this age. On the first study (Figure 1A), T2-weighted images showed a mildly expansile, hyperintense intraaxial lesion that was centered in the anterior left temporal lobe and extended posteriorly and superiorly into the inferior parietal lobule. This lesion disproportionately involved the subcortical white matter, although the cortex was also affected. There was no evidence of associated restricted diffusion or magnetic susceptibility effect and no abnormal enhancement on contrast-enhanced images. On the two subsequent studies (Figure 1B and 1C), the lesion maintained similar signal characteristics but decreased in size; in fact, the third study revealed that the lesion had resolved almost completely. The results of magnetic resonance angiography and venography were normal.

Table 1.

Laboratory Data.
Dr. Reda: On the patient’s admission to the other hospital, 1 year before presentation to this hospital, laboratory testing revealed mild anemia, with a mean corpuscular volume of 65 fl (reference range, 79 to 92); other test results, including the results of cerebrospinal fluid analysis, are shown in Table 1. A diagnosis of stroke was made, and therapy with aspirin and a lipid-lowering agent was begun. The patient was discharged home. His language abilities gradually improved over the next 2 months but did not return to baseline, and his headaches persisted.

One month after discharge, while the patient was at home, he had a generalized tonic–clonic seizure that was witnessed by his wife. Therapy with levetiracetam was begun, and no further seizure activity occurred. During the next 11 months, he had fluctuating focal neurologic symptoms, rapidly progressive cognitive decline, weakness, and gait instability, along with nearly daily diffuse headaches, muscle cramps in his calves, and weight loss of 11 kg.

One month before the patient’s presentation to this hospital, blood levels of cholesterol and lipids and results of liver- and renal-function tests were normal; other test results are shown in Table 1. During the 2 weeks before presentation, the patient’s wife noted that his behavior had become more childlike, with rambling speech, impulsivity, and anger. His gait, balance, and coordination worsened, although he did not fall, and swallowing difficulties developed. He was referred to the neurology clinic at this hospital.

The patient was right-handed. He had congenital short stature. When he was 25 years of age, sensorineural hearing loss (worse on the right side than on the left) developed; it gradually worsened and led to the use of hearing aids. Proteinuria was noted when he was 25 years of age. In the past, a clinical diagnosis of gout had been made after an episode of swelling and pain in the left big toe. Medications were levetiracetam, lisinopril, and a multivitamin. He had no known allergies. He was married, had a young child, and had lived in the southwestern United States until 3 weeks before this presentation, when his family moved to be near relatives in New England. He was a lawyer but had been receiving disability benefits since the onset of this illness. He drank alcohol in moderation and smoked tobacco occasionally. His mother was of French Canadian and Irish descent; she had reportedly had lupus nephritis with antinuclear antibodies, diabetes mellitus, and colitis and was described as needing rest frequently when walking. His father was of Hungarian and Italian descent and had diabetes mellitus and coronary artery disease. A maternal aunt and uncle had diabetes mellitus, and the same uncle also had sensorineural hearing loss. He had nine siblings who ranged in height from 150 to 163 cm; some were reportedly well and others had mild gastrointestinal dysmotility or symptoms of the irritable bowel syndrome, sensorineural hearing loss, anxiety, and _-thalassemia trait.

On examination, the patient appeared cachectic. The blood pressure was 112/72 mm Hg, the pulse 83 beats per minute, the temperature 36.8°C, and the oxygen saturation 99% while he was breathing ambient air. His weight was 40.5 kg, and his height 152 cm. During the examination, he reached out to grab the examiner’s hand and glasses inappropriately. The Montreal Cognitive Assessment score was 25 on a scale ranging from 0 to 30 (with higher scores indicating better cognitive function); points were deducted because the patient made errors of visuospatial function, repetition, and fluency and incorrectly identified a glove as a hand and a feather as a leaf. He had ataxic dysarthria with telegraphic speech and frequent tangential ramblings that were difficult to interrupt. The optic disks were flat and without pallor. The visual fields were normal on confrontation testing. The pupils were round, equal, and reactive, without Horner’s syndrome or a relative afferent pupillary defect. Upward gaze was markedly restricted, lateral gaze moderately restricted, and downward gaze mildly restricted in each eye. There was mild bifacial weakness and markedly impaired hearing bilaterally, even while the patient was wearing hearing aids. There was minimal weakness of shoulder abduction bilaterally. The muscle bulk, tone, and strength of the neck and limbs were otherwise normal, without tremor, other adventitious movements, or fasciculations. Finger–nose–finger and heel–knee–shin testing revealed subtle dysmetria; rapid alternating movements were slightly irregular. No truncal ataxia was present while the patient was seated. He swayed prominently while he stood with his feet together and eyes closed. His gait was mildly ataxic, and he could not take more than two tandem steps without losing his balance. The remainder of the neurologic and general examinations was normal.

Laboratory testing revealed a mild secondary carnitine deficiency, which was thought to be dietary. The lactic acid level was initially normal but subsequently increased and remained elevated; the highest level was 8.3 mmol per liter (75 mg per deciliter; reference range, 0.5 to 2.2 mmol per liter [5 to 20 mg per deciliter]). Other test results are shown in Table 1.

Diagnostic procedures were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease. The patient's symptoms of seizures, weakness, cognitive decline, and personality changes, along with his history of sensorineural hearing loss and proteinuria, suggest a systemic disorder. The MRI findings of global brain parenchymal volume loss and a lesion in the left temporal lobe are consistent with a neurodegenerative process. The patient's history of gout, sensorineural hearing loss, and proteinuria at a young age, along with his family history of similar symptoms, suggest a genetic disorder. The patient's short stature, lactic acidosis, and secondary carnitine deficiency are consistent with a mitochondrial disorder. MNGIE disease is a rare autosomal recessive disorder characterized by progressive damage to the nervous system, gastrointestinal dysmotility, and abnormalities in multiple organ systems. It is caused by mutations in the TYMP gene, which leads to a deficiency of the enzyme thymidine phosphorylase, resulting in an accumulation of thymidine and deoxyuridine in tissues and body fluids. This imbalance leads to mitochondrial dysfunction, which can cause the wide range of symptoms seen in this patient.""
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        ""content"": ""The patient's symptoms include seizures, weakness, cognitive decline, personality changes, difficulty speaking, headaches, muscle cramps, weight loss, and sensorineural hearing loss. The patient also has a history of proteinuria and gout. The MRI shows global brain parenchymal volume loss and a lesion in the anterior left temporal lobe. The patient's family history includes lupus nephritis, diabetes mellitus, and sensorineural hearing loss. The patient's symptoms, MRI findings, and family history suggest a genetic disorder. The patient's short stature, sensorineural hearing loss, and proteinuria suggest Alport syndrome, but this does not explain all of the patient's symptoms. The patient's cognitive decline, personality changes, and MRI findings suggest a neurodegenerative disorder. The patient's family history of lupus nephritis and diabetes mellitus suggest a disorder that affects multiple organ systems. The patient's lactic acidosis suggests a mitochondrial disorder. Taken together, these findings suggest a mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease.\n\nDiagnosis: Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease.""
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}",Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease,N,"{
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        ""content"": ""This is a 41-year-old man with a history of migraines, sensorineural hearing loss, and chronic proteinuria who presents with seizures, weakness, and cognitive decline. His symptoms have been progressive over the past two years, with personality changes, language difficulties, headaches, and weight loss. His family history is significant for sensorineural hearing loss, diabetes, and lupus nephritis. His physical exam is notable for cachexia, ataxic dysarthria, telegraphic speech, impaired hearing, mild bifacial weakness, and mild ataxia. His lab results show mild anemia and secondary carnitine deficiency. His MRI shows global brain parenchymal volume loss and a hyperintense intraaxial lesion in the left temporal lobe. \n\nThe differential diagnosis for this patient includes neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, or Huntington's disease, metabolic disorders such as mitochondrial diseases, and autoimmune or inflammatory conditions such as lupus or vasculitis. \n\nAlzheimer's disease typically presents with memory loss, which this patient does not have. Parkinson's disease usually presents with tremors, rigidity, and bradykinesia, which this patient also does not have. Huntington's disease could present with personality changes and cognitive decline, but this patient does not have the characteristic chorea. \n\nMitochondrial diseases can present with a wide range of symptoms affecting multiple organ systems, including the nervous system, and can cause lactic acidosis, which this patient has. This patient's history of migraines, sensorineural hearing loss, and proteinuria could also be consistent with a mitochondrial disease. \n\nAutoimmune or inflammatory conditions could cause the patient's symptoms, but his lab results do not show any signs of inflammation, and his family history of lupus is not necessarily indicative of an autoimmune condition in this patient. \n\nGiven the patient's symptoms, family history, and lab results, a mitochondrial disease is the most likely diagnosis. \n\nDiagnosis: Mitochondrial disease.""
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10.1056/NEJMcpc1616395,Case 12-2017 — A 34-Year-Old Man with Nephropathy,,Collapsing variant of focal segmental glomerulosclerosis that is consistent with HIV-associated nephropathy.,Collapsing variant of focal segmental glomerulosclerosis (HIV-associated nephropathy) and acute tubular injury due to contrast-induced nephropathy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:         A 34-year-old man with hearing impairment was admitted to this hospital because of worsening renal function.

The patient had been well until approximately 11 weeks before this admission, when subjective fevers with sweats, fatigue, decreased appetite, and nausea developed. He initially attributed these symptoms, which worsened over the next 2 months, to the hot weather. Cough and shortness of breath on exertion also developed during that time, and the patient noted that his urine appeared foamy. He reportedly lost 9 kg.

Twenty-two days before this admission, the patient presented to the emergency department at another hospital for evaluation. The blood creatinine level was 0.8 mg per deciliter (71 _mol per liter; normal range, 0.6 to 1.5 mg per deciliter [53 to 133 _mol per liter]), and the blood urea nitrogen level was 7 mg per deciliter (2.5 mmol per liter; normal range, 8 to 25 mg per deciliter [2.9 to 8.9 mmol per liter]). The patient left the hospital without being evaluated by a physician.

Table 1.

Laboratory Data.
The patient returned to the emergency department at the other hospital 1 week later (15 days before this admission) and reported that he had been having malaise, vomiting, and chest pain for the past 2 days. The chest pain worsened during inspiration. On examination, the temperature was 36.6°C, the pulse 76 beats per minute, the blood pressure 110/73 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 95% while he was breathing ambient air. He had hearing aids in both ears and nontender, enlarged lymph nodes in the neck. Breath sounds were diminished bilaterally, and faint rhonchi were heard at the base of both lungs on auscultation. The abdomen was soft and flat, with mild, diffuse tenderness on palpation; the remainder of the examination was normal. The platelet count, red-cell indexes, and anion gap were normal, as were blood levels of glucose, alkaline phosphatase, total bilirubin, direct bilirubin, lipase, and lactic acid; the results of other laboratory tests are shown in Table 1. Urinalysis revealed cloudy, amber urine with a specific gravity of 1.037, a pH of 5.0, a moderate amount of occult blood, a protein level of at least 500 mg per deciliter, a glucose level of 50 mg per deciliter, and a ketone level of 20 mg per deciliter by dipstick; on microscopic examination, there were 0 to 2 red cells and 10 to 25 white cells per high-power field and a moderate amount of hyaline casts. An electrocardiogram showed no evidence of cardiac ischemia.

Dr. Grace C. Lo: Computed tomographic (CT) angiography of the chest, performed after the administration of intravenous contrast material, revealed mild subpleural interlobular septal thickening without lobar consolidation or evidence of acute pulmonary embolism.

Dr. Katz: While the patient was in the emergency department, the temperature rose to 37.9°C, and he reported malaise. Blood samples were obtained for culture, and acetaminophen was administered. The patient was admitted to the other hospital.

Intravenous fluids were administered. By the next day, the chest pain had resolved. The platelet count, red-cell indexes, and anion gap were normal, as were blood levels of glucose, alkaline phosphatase, total bilirubin, direct bilirubin, and lactic acid; the results of other laboratory tests are shown in Table 1.

Figure 1.

Abdominal Imaging Studies.
Dr. Lo: Noninvasive ultrasonography of both legs was performed and did not reveal evidence of deep venous thrombosis. A prominent inguinal lymph node (1.5 cm by 0.6 cm by 1.5 cm) was seen on the right side. On ultrasonography of the abdomen, there was borderline enlargement of the spleen, which measured 13.3 cm in length (normal range, ≤12). The right kidney measured 12.3 cm in length, and the left kidney measured 12.4 cm in length; markedly echogenic renal parenchyma was present bilaterally (Figure 1A).

Dr. Katz: Transthoracic echocardiography revealed a left ventricular ejection fraction of 60 to 65% and no pericardial effusion. The administration of intravenous fluids was continued. On the third hospital day, the platelet count, red-cell indexes, and anion gap were normal, as were blood levels of glucose, alkaline phosphatase, total bilirubin, direct bilirubin, C3, and C4; tests for antiproteinase 3 antibodies and antimyeloperoxidase antibodies were negative. Urinalysis revealed cloudy, amber urine with a specific gravity of 1.040, a pH of 5.0, a moderate amount of blood, a protein level of at least 500 mg per deciliter, a glucose level of 50 mg per deciliter, and a ketone level of 20 mg per deciliter by dipstick; on microscopic examination, there were 0 to 2 red cells and 10 to 25 white cells per high-power field, few white-cell clumps, and occasional hyaline casts. The urinary creatinine level was 298 mg per deciliter (normal range, 20 to 370), and the urinary total protein level was higher than 2500 mg per deciliter (normal range, 5 to 25 [other hospital]).

Dr. Lo: CT of the abdomen and pelvis, performed without the administration of contrast material, revealed patchy atelectasis of the lung bases, mild left paraaortic retroperitoneal lymphadenopathy, persistent bilateral enhancement of the kidneys (related to the previous administration of contrast material), and trace free fluid in the pelvis (Figure 1B and 1C).

Dr. Katz: A diagnostic test result was received, and medical therapy was initiated.

During the next 8 days, edema of the lower legs developed. Furosemide, calcium acetate, sodium bicarbonate, and a multivitamin were administered. The patient continued to produce urine. Laboratory test results obtained on the 11th hospital day (5 days before admission) are shown in Table 1; furosemide was discontinued. The next day, a tunneled hemodialysis catheter was inserted in the right internal jugular vein. The patient underwent three sessions of hemodialysis during the next 4 days. On the 16th hospital day, he was transferred to this hospital for further evaluation and treatment.

On admission to this hospital, the patient reported that the leg swelling had improved and that he felt well. He had a history of anxiety. When he was 7 years of age, he was struck by a motor vehicle as a pedestrian; thereafter, progressive bilateral hearing loss developed. Before admission to the other hospital, the patient had been taking no medications; he had an allergy to ibuprofen, which caused a rash. He worked as a laborer and lived with a friend in an urban area of New England. He had separated from the female partner with whom he had two children, and he had sex with men and women. He had never received a transfusion of blood products. Approximately 6 weeks earlier, he had been in a fistfight with another person, and blood from that person made contact with open wounds on his hands and near his eyes. He had smoked a half pack of cigarettes per day for the past 15 years, and he used marijuana; he did not drink alcohol or use other illicit drugs. His mother had coronary artery disease, and he did not know his father; there was no known family history of kidney disease.

On examination, the patient appeared well. The temperature was 37.2°C, the pulse 76 beats per minute, the blood pressure 138/93 mm Hg, and the respiratory rate 18 breaths per minute. The weight was 82 kg. A hemodialysis catheter exiting the right chest was present, and there was 2+ pitting edema of the legs to the mid-shins; the remainder of the examination was normal. The results of laboratory tests are shown in Table 1. During the first 24 hours, the patient drank 890 ml of fluid and had 4425 ml of urine output. Urinalysis revealed clear, yellow urine with a specific gravity of 1.008, a pH of 8.0, 3+ glucose, 2+ protein, and 1+ blood by dipstick, as well as 0 to 2 red cells per high-power field. The urine osmolality was 277 mOsm per kilogram of water (normal range, 15 to 1150). The urinary level of creatinine was 47 mg per deciliter, total protein 368.5 mg per deciliter (normal range, 0 to 13.5 [this hospital]), microalbumin 194.5 mg per deciliter (normal range, 0 to 2.0), and sodium 84 mmol per liter. An additional diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                A 34-year-old man with hearing impairment was admitted to this hospital because of worsening renal function.

The patient had been well until approximately 11 weeks before this admission, when subjective fevers with sweats, fatigue, decreased appetite, and nausea developed. He initially attributed these symptoms, which worsened over the next 2 months, to the hot weather. Cough and shortness of breath on exertion also developed during that time, and the patient noted that his urine appeared foamy. He reportedly lost 9 kg.

Twenty-two days before this admission, the patient presented to the emergency department at another hospital for evaluation. The blood creatinine level was 0.8 mg per deciliter (71 _mol per liter; normal range, 0.6 to 1.5 mg per deciliter [53 to 133 _mol per liter]), and the blood urea nitrogen level was 7 mg per deciliter (2.5 mmol per liter; normal range, 8 to 25 mg per deciliter [2.9 to 8.9 mmol per liter]). The patient left the hospital without being evaluated by a physician.

Table 1.

Laboratory Data.
The patient returned to the emergency department at the other hospital 1 week later (15 days before this admission) and reported that he had been having malaise, vomiting, and chest pain for the past 2 days. The chest pain worsened during inspiration. On examination, the temperature was 36.6°C, the pulse 76 beats per minute, the blood pressure 110/73 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 95% while he was breathing ambient air. He had hearing aids in both ears and nontender, enlarged lymph nodes in the neck. Breath sounds were diminished bilaterally, and faint rhonchi were heard at the base of both lungs on auscultation. The abdomen was soft and flat, with mild, diffuse tenderness on palpation; the remainder of the examination was normal. The platelet count, red-cell indexes, and anion gap were normal, as were blood levels of glucose, alkaline phosphatase, total bilirubin, direct bilirubin, lipase, and lactic acid; the results of other laboratory tests are shown in Table 1. Urinalysis revealed cloudy, amber urine with a specific gravity of 1.037, a pH of 5.0, a moderate amount of occult blood, a protein level of at least 500 mg per deciliter, a glucose level of 50 mg per deciliter, and a ketone level of 20 mg per deciliter by dipstick; on microscopic examination, there were 0 to 2 red cells and 10 to 25 white cells per high-power field and a moderate amount of hyaline casts. An electrocardiogram showed no evidence of cardiac ischemia.

Dr. Grace C. Lo: Computed tomographic (CT) angiography of the chest, performed after the administration of intravenous contrast material, revealed mild subpleural interlobular septal thickening without lobar consolidation or evidence of acute pulmonary embolism.

Dr. Katz: While the patient was in the emergency department, the temperature rose to 37.9°C, and he reported malaise. Blood samples were obtained for culture, and acetaminophen was administered. The patient was admitted to the other hospital.

Intravenous fluids were administered. By the next day, the chest pain had resolved. The platelet count, red-cell indexes, and anion gap were normal, as were blood levels of glucose, alkaline phosphatase, total bilirubin, direct bilirubin, and lactic acid; the results of other laboratory tests are shown in Table 1.

Figure 1.

Abdominal Imaging Studies.
Dr. Lo: Noninvasive ultrasonography of both legs was performed and did not reveal evidence of deep venous thrombosis. A prominent inguinal lymph node (1.5 cm by 0.6 cm by 1.5 cm) was seen on the right side. On ultrasonography of the abdomen, there was borderline enlargement of the spleen, which measured 13.3 cm in length (normal range, ≤12). The right kidney measured 12.3 cm in length, and the left kidney measured 12.4 cm in length; markedly echogenic renal parenchyma was present bilaterally (Figure 1A).

Dr. Katz: Transthoracic echocardiography revealed a left ventricular ejection fraction of 60 to 65% and no pericardial effusion. The administration of intravenous fluids was continued. On the third hospital day, the platelet count, red-cell indexes, and anion gap were normal, as were blood levels of glucose, alkaline phosphatase, total bilirubin, direct bilirubin, C3, and C4; tests for antiproteinase 3 antibodies and antimyeloperoxidase antibodies were negative. Urinalysis revealed cloudy, amber urine with a specific gravity of 1.040, a pH of 5.0, a moderate amount of blood, a protein level of at least 500 mg per deciliter, a glucose level of 50 mg per deciliter, and a ketone level of 20 mg per deciliter by dipstick; on microscopic examination, there were 0 to 2 red cells and 10 to 25 white cells per high-power field, few white-cell clumps, and occasional hyaline casts. The urinary creatinine level was 298 mg per deciliter (normal range, 20 to 370), and the urinary total protein level was higher than 2500 mg per deciliter (normal range, 5 to 25 [other hospital]).

Dr. Lo: CT of the abdomen and pelvis, performed without the administration of contrast material, revealed patchy atelectasis of the lung bases, mild left paraaortic retroperitoneal lymphadenopathy, persistent bilateral enhancement of the kidneys (related to the previous administration of contrast material), and trace free fluid in the pelvis (Figure 1B and 1C).

Dr. Katz: A diagnostic test result was received, and medical therapy was initiated.

During the next 8 days, edema of the lower legs developed. Furosemide, calcium acetate, sodium bicarbonate, and a multivitamin were administered. The patient continued to produce urine. Laboratory test results obtained on the 11th hospital day (5 days before admission) are shown in Table 1; furosemide was discontinued. The next day, a tunneled hemodialysis catheter was inserted in the right internal jugular vein. The patient underwent three sessions of hemodialysis during the next 4 days. On the 16th hospital day, he was transferred to this hospital for further evaluation and treatment.

On admission to this hospital, the patient reported that the leg swelling had improved and that he felt well. He had a history of anxiety. When he was 7 years of age, he was struck by a motor vehicle as a pedestrian; thereafter, progressive bilateral hearing loss developed. Before admission to the other hospital, the patient had been taking no medications; he had an allergy to ibuprofen, which caused a rash. He worked as a laborer and lived with a friend in an urban area of New England. He had separated from the female partner with whom he had two children, and he had sex with men and women. He had never received a transfusion of blood products. Approximately 6 weeks earlier, he had been in a fistfight with another person, and blood from that person made contact with open wounds on his hands and near his eyes. He had smoked a half pack of cigarettes per day for the past 15 years, and he used marijuana; he did not drink alcohol or use other illicit drugs. His mother had coronary artery disease, and he did not know his father; there was no known family history of kidney disease.

On examination, the patient appeared well. The temperature was 37.2°C, the pulse 76 beats per minute, the blood pressure 138/93 mm Hg, and the respiratory rate 18 breaths per minute. The weight was 82 kg. A hemodialysis catheter exiting the right chest was present, and there was 2+ pitting edema of the legs to the mid-shins; the remainder of the examination was normal. The results of laboratory tests are shown in Table 1. During the first 24 hours, the patient drank 890 ml of fluid and had 4425 ml of urine output. Urinalysis revealed clear, yellow urine with a specific gravity of 1.008, a pH of 8.0, 3+ glucose, 2+ protein, and 1+ blood by dipstick, as well as 0 to 2 red cells per high-power field. The urine osmolality was 277 mOsm per kilogram of water (normal range, 15 to 1150). The urinary level of creatinine was 47 mg per deciliter, total protein 368.5 mg per deciliter (normal range, 0 to 13.5 [this hospital]), microalbumin 194.5 mg per deciliter (normal range, 0 to 2.0), and sodium 84 mmol per liter. An additional diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""HIV-associated nephropathy (HIVAN). The patient's symptoms of fever, fatigue, decreased appetite, and nausea, along with the presence of foamy urine and weight loss, suggest kidney disease. The patient's history of unprotected sex with multiple partners and contact with another person's blood during a fistfight are risk factors for HIV infection. The patient's hearing impairment could be related to HIV infection, as HIV can cause a variety of neurological complications. The patient's worsening renal function, proteinuria, and the findings of echogenic renal parenchyma on ultrasound are consistent with HIVAN.""
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        ""content"": ""The patient presents with symptoms of fever, fatigue, decreased appetite, nausea, cough, shortness of breath, and foamy urine. He also has a history of hearing impairment. His lab results show elevated creatinine levels and proteinuria, indicating kidney dysfunction. The patient's symptoms, along with his hearing impairment and renal dysfunction, suggest Alport syndrome, a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. \n\nDiagnosis: Alport Syndrome""
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        ""content"": ""This is a 34-year-old man with a history of hearing impairment who presents with worsening renal function, subjective fevers, sweats, fatigue, decreased appetite, nausea, cough, shortness of breath, and foamy urine. The differential diagnosis for this patient includes nephrotic syndrome, glomerulonephritis, HIV-associated nephropathy, and systemic lupus erythematosus (SLE). The patient's urinalysis shows proteinuria and hematuria, which is suggestive of a glomerular disease. The patient's history of hearing loss could be associated with Alport syndrome, a genetic disorder characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. However, the patient's acute symptoms and rapid decline in renal function are not typical for Alport syndrome. The patient's symptoms and lab findings are not suggestive of SLE. The patient has risk factors for HIV, including having sex with men and women and exposure to another person's blood during a fistfight. HIV can cause a variety of kidney diseases, including HIV-associated nephropathy, which can present with rapidly progressive renal failure and heavy proteinuria, as seen in this patient. Therefore, HIV-associated nephropathy is the most likely diagnosis.\n\nDiagnosis: HIV-associated nephropathy.""
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10.1056/NEJMcpc1616023,"Case 11-2017 — A 61-Year-Old Woman with Leg Swelling, Back Pain, and Hydronephrosis",,Follicular lymphoma (grade 1–2 of 3; stage IV of IV) with a follicular pattern.,"Indolent lymphoma, most likely follicular lymphoma.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 A 61-year-old woman was seen in the emergency department of this hospital because of leg swelling and back pain.

The patient had been in her usual health until approximately 3 months before this presentation, when mild swelling of her left leg developed. Three days before this presentation, pain in the back, both flanks, and left leg developed and the leg swelling increased. She came to the emergency department of this hospital.

The patient reported no trauma, fevers, night sweats, or weight loss. She had arthritis, asthma, hypercholesterolemia, hypertension, and non–insulin-dependent type 2 diabetes mellitus. In the remote past, she had reportedly had a positive tuberculin skin test. She had undergone a partial colectomy for resection of a stage T1 colon cancer (without adjuvant chemotherapy) 7 years earlier, as well as a lumpectomy of the left breast, a laparoscopic cholecystectomy, and a total abdominal hysterectomy and bilateral salpingo-oophorectomy for benign disease. Medications included metformin, triamterene–hydrochlorothiazide, amlodipine, atorvastatin, aspirin, loratadine, and, as needed, an albuterol inhaler. She had no known allergies. She did not smoke, drink alcohol, or use illicit drugs. She was widowed and of African-American ancestry. Her father had had Alzheimer’s disease and diabetes mellitus; her mother had had heart disease and breast cancer; a sister had breast cancer; a brother had hypertension, hypercholesterolemia, and coronary artery disease; and two brothers had had diabetes mellitus and had died before they were 70 years of age. Her children and grandchildren were healthy.

On examination, the blood pressure was 150/77 mm Hg, and the pulse 75 beats per minute; the temperature, respiratory rate, and oxygen saturation were normal. There was paraspinal tenderness in the lumbar region and mild (1+) nonpitting edema of the left calf and ankle; the remainder of the examination was normal. The hematocrit was 33.8% (reference range, 36.0 to 46.0), the hemoglobin level 11.3 g per deciliter (reference range, 12.0 to 16.0), and the d-dimer level 2079 ng per milliliter (reference range, <500). The white-cell count, differential count, platelet count, red-cell indexes, prothrombin time, prothrombin-time international normalized ratio, results of renal- and liver-function tests, and a urinalysis were normal, as were blood levels of electrolytes, calcium, phosphorus, magnesium, glucose, total protein, albumin, and globulin; testing for creatine kinase isoenzymes and troponin I was negative. An electrocardiogram showed sinus rhythm with nonspecific ST-segment and T-wave abnormalities that were more marked than those seen on an electrocardiogram obtained 8 months earlier. Noninvasive studies of the legs revealed no evidence of deep venous thrombosis.

Figure 1.

Initial CT Scans.
Dr. Victorine V. Muse: On the patient’s presentation to the emergency department, computed tomography (CT) of the chest was performed after the administration of contrast material, in accordance with a pulmonary-embolism protocol. A right apical soft-tissue lesion (4.0 cm in cross-sectional diameter) that extended into the lateral chest wall was present (Figure 1A). Enlarged bilateral axillary lymph nodes (up to 1.8 cm in cross-sectional diameter) were also present (Figure 1B), and enlarged bilateral hilar lymph nodes (1.0 cm in cross-sectional diameter) were present without other mediastinal lymphadenopathy. CT images of the lower chest and a CT angiogram that included the upper abdomen showed the superior aspect of a large retroperitoneal soft-tissue mass that extended into both kidneys, as well as hydronephrosis of the right kidney (Figure 1C). Abdominal and pelvic CT to further evaluate the mass was recommended.

Dr. El-Jawahri: Three days later, the patient was seen by her internist. On examination, the blood pressure was 160/90 mm Hg, the pulse 80 beats per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 30.8. An enlarged lymph node (1.0 cm in cross-sectional diameter) was detected on palpation under the pectoralis major muscle in the anterior right axilla. The remainder of the examination was normal. The hematocrit, hemoglobin level, white-cell count, and differential count were stable. The reticulocyte count was 2.6% (reference range, 0.5 to 2.5), and the blood uric acid level was 7.1 mg per deciliter (422 _mol per liter; reference range, 2.3 to 6.6 mg per deciliter [137 to 393 _mol per liter]). Blood levels of iron, iron-binding capacity, ferritin, lactate dehydrogenase, and carcinoembryonic antigen were normal, as were the results of renal-function tests. Cytologic examination of the urine revealed reactive transitional cells and neutrophils but no malignant cells.

Dr. Muse: CT of the chest, abdomen, and pelvis, performed 3 days after the patient’s presentation to the emergency department, revealed a massive conglomerate of enlarged lymph nodes; it extended from the level of the celiac axis to below the aortic bifurcation and into the pelvis, and it resulted in marked attenuation of the renal vessels and inferior vena cava, hydronephrosis of the right kidney, and infiltration of soft tissue into the left kidney (Figure 1D). The soft-tissue abnormality extended into the small-bowel mesentery (Figure 1E) and along the pelvic sidewalls. The liver and spleen were normal, as were all the other abdominal organs and the bowel.

Dr. El-Jawahri: The next day, the patient was seen by a urologist, and 8 days after that, she was seen by a surgeon, who recommended a retroperitoneal biopsy. Two weeks after her initial presentation, she was seen again by her internist. The patient reported intermittent edema of the left leg with mild pain, dyspnea on exertion, moderate discomfort in the left lower abdomen, and night sweats. On examination, enlarged lymph nodes were detected on palpation under the pectoralis muscles bilaterally, and the left thigh and calf were edematous, without tenderness or tension. Two days later, repeat CT of the abdomen and pelvis was performed, and the results were unchanged from previous studies. The hematocrit, hemoglobin level, and white-cell count were stable; blood levels of electrolytes and lactate dehydrogenase and results of coagulation and renal- and liver-function tests were normal.

Twenty-four days after the patient’s initial presentation, a diagnostic procedure was performed, and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  A 61-year-old woman was seen in the emergency department of this hospital because of leg swelling and back pain.

The patient had been in her usual health until approximately 3 months before this presentation, when mild swelling of her left leg developed. Three days before this presentation, pain in the back, both flanks, and left leg developed and the leg swelling increased. She came to the emergency department of this hospital.

The patient reported no trauma, fevers, night sweats, or weight loss. She had arthritis, asthma, hypercholesterolemia, hypertension, and non–insulin-dependent type 2 diabetes mellitus. In the remote past, she had reportedly had a positive tuberculin skin test. She had undergone a partial colectomy for resection of a stage T1 colon cancer (without adjuvant chemotherapy) 7 years earlier, as well as a lumpectomy of the left breast, a laparoscopic cholecystectomy, and a total abdominal hysterectomy and bilateral salpingo-oophorectomy for benign disease. Medications included metformin, triamterene–hydrochlorothiazide, amlodipine, atorvastatin, aspirin, loratadine, and, as needed, an albuterol inhaler. She had no known allergies. She did not smoke, drink alcohol, or use illicit drugs. She was widowed and of African-American ancestry. Her father had had Alzheimer’s disease and diabetes mellitus; her mother had had heart disease and breast cancer; a sister had breast cancer; a brother had hypertension, hypercholesterolemia, and coronary artery disease; and two brothers had had diabetes mellitus and had died before they were 70 years of age. Her children and grandchildren were healthy.

On examination, the blood pressure was 150/77 mm Hg, and the pulse 75 beats per minute; the temperature, respiratory rate, and oxygen saturation were normal. There was paraspinal tenderness in the lumbar region and mild (1+) nonpitting edema of the left calf and ankle; the remainder of the examination was normal. The hematocrit was 33.8% (reference range, 36.0 to 46.0), the hemoglobin level 11.3 g per deciliter (reference range, 12.0 to 16.0), and the d-dimer level 2079 ng per milliliter (reference range, <500). The white-cell count, differential count, platelet count, red-cell indexes, prothrombin time, prothrombin-time international normalized ratio, results of renal- and liver-function tests, and a urinalysis were normal, as were blood levels of electrolytes, calcium, phosphorus, magnesium, glucose, total protein, albumin, and globulin; testing for creatine kinase isoenzymes and troponin I was negative. An electrocardiogram showed sinus rhythm with nonspecific ST-segment and T-wave abnormalities that were more marked than those seen on an electrocardiogram obtained 8 months earlier. Noninvasive studies of the legs revealed no evidence of deep venous thrombosis.

Figure 1.

Initial CT Scans.
Dr. Victorine V. Muse: On the patient’s presentation to the emergency department, computed tomography (CT) of the chest was performed after the administration of contrast material, in accordance with a pulmonary-embolism protocol. A right apical soft-tissue lesion (4.0 cm in cross-sectional diameter) that extended into the lateral chest wall was present (Figure 1A). Enlarged bilateral axillary lymph nodes (up to 1.8 cm in cross-sectional diameter) were also present (Figure 1B), and enlarged bilateral hilar lymph nodes (1.0 cm in cross-sectional diameter) were present without other mediastinal lymphadenopathy. CT images of the lower chest and a CT angiogram that included the upper abdomen showed the superior aspect of a large retroperitoneal soft-tissue mass that extended into both kidneys, as well as hydronephrosis of the right kidney (Figure 1C). Abdominal and pelvic CT to further evaluate the mass was recommended.

Dr. El-Jawahri: Three days later, the patient was seen by her internist. On examination, the blood pressure was 160/90 mm Hg, the pulse 80 beats per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 30.8. An enlarged lymph node (1.0 cm in cross-sectional diameter) was detected on palpation under the pectoralis major muscle in the anterior right axilla. The remainder of the examination was normal. The hematocrit, hemoglobin level, white-cell count, and differential count were stable. The reticulocyte count was 2.6% (reference range, 0.5 to 2.5), and the blood uric acid level was 7.1 mg per deciliter (422 _mol per liter; reference range, 2.3 to 6.6 mg per deciliter [137 to 393 _mol per liter]). Blood levels of iron, iron-binding capacity, ferritin, lactate dehydrogenase, and carcinoembryonic antigen were normal, as were the results of renal-function tests. Cytologic examination of the urine revealed reactive transitional cells and neutrophils but no malignant cells.

Dr. Muse: CT of the chest, abdomen, and pelvis, performed 3 days after the patient’s presentation to the emergency department, revealed a massive conglomerate of enlarged lymph nodes; it extended from the level of the celiac axis to below the aortic bifurcation and into the pelvis, and it resulted in marked attenuation of the renal vessels and inferior vena cava, hydronephrosis of the right kidney, and infiltration of soft tissue into the left kidney (Figure 1D). The soft-tissue abnormality extended into the small-bowel mesentery (Figure 1E) and along the pelvic sidewalls. The liver and spleen were normal, as were all the other abdominal organs and the bowel.

Dr. El-Jawahri: The next day, the patient was seen by a urologist, and 8 days after that, she was seen by a surgeon, who recommended a retroperitoneal biopsy. Two weeks after her initial presentation, she was seen again by her internist. The patient reported intermittent edema of the left leg with mild pain, dyspnea on exertion, moderate discomfort in the left lower abdomen, and night sweats. On examination, enlarged lymph nodes were detected on palpation under the pectoralis muscles bilaterally, and the left thigh and calf were edematous, without tenderness or tension. Two days later, repeat CT of the abdomen and pelvis was performed, and the results were unchanged from previous studies. The hematocrit, hemoglobin level, and white-cell count were stable; blood levels of electrolytes and lactate dehydrogenase and results of coagulation and renal- and liver-function tests were normal.

Twenty-four days after the patient’s initial presentation, a diagnostic procedure was performed, and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of leg swelling and back pain, along with the CT scan findings of a large retroperitoneal soft-tissue mass and enlarged lymph nodes, suggest a malignancy. The patient's history of colon cancer and breast lumpectomy also increase the likelihood of a cancer diagnosis. The absence of deep venous thrombosis and the presence of a large retroperitoneal mass that extends into both kidneys and causes hydronephrosis of the right kidney further support a diagnosis of cancer. The patient's stable hematocrit, hemoglobin level, and white-cell count, along with normal blood levels of electrolytes and lactate dehydrogenase and normal results of coagulation and renal- and liver-function tests, do not provide additional clues to the diagnosis. The diagnostic procedure performed 24 days after the patient's initial presentation likely confirmed the diagnosis.\n\nDiagnosis: Retroperitoneal malignancy.""
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        ""content"": ""The patient's symptoms of leg swelling and back pain, along with the CT findings of a large retroperitoneal soft-tissue mass extending into both kidneys, enlarged lymph nodes, and a right apical soft-tissue lesion, suggest a malignancy. The patient's history of colon cancer and breast lumpectomy, as well as a family history of breast cancer, further support this. The absence of deep venous thrombosis and the presence of nonpitting edema in the left calf and ankle suggest that the leg swelling is likely due to obstruction from the retroperitoneal mass. The back and flank pain could be due to the mass pressing on nerves or other structures. The patient's stable hematocrit, hemoglobin level, and white-cell count suggest that the malignancy is not significantly affecting her bone marrow function. The normal results of renal- and liver-function tests suggest that these organs are currently functioning well despite the presence of the mass.\n\nDiagnosis: Metastatic cancer, likely of breast or colon origin.""
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}","Metastatic cancer, likely of breast or colon origin",N,"{
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        ""content"": ""The patient is a 61-year-old woman with a history of colon cancer, presenting with leg swelling, back pain, and a large retroperitoneal mass. The differential diagnosis includes recurrence of colon cancer, lymphoma, and other malignancies such as ovarian or renal cell carcinoma. The patient's history of colon cancer raises the possibility of recurrence, but the absence of gastrointestinal symptoms and the presence of a large retroperitoneal mass are more suggestive of lymphoma or another malignancy. The patient's symptoms of leg swelling and back pain could be due to compression of the inferior vena cava or renal vessels by the mass. The presence of enlarged lymph nodes in the chest and axilla also suggests a systemic process such as lymphoma. The absence of malignant cells on urine cytology makes renal cell carcinoma less likely. Given the patient's symptoms, imaging findings, and history, lymphoma is the most likely diagnosis.\n\nDiagnosis: Lymphoma.""
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10.1056/NEJMcpc1616020,Case 10-2017 — A 6-Month-Old Boy with Gastrointestinal Bleeding and Abdominal Pain,,Meckel’s diverticulum with heterotopic gastric mucosa and associated peptic ulceration in the intestinal mucosa.,Meckel’s diverticulum with heterotopic gastric mucosa and associated peptic ulceration in the intestinal mucosa.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 6-month-old boy was seen in the emergency department of this hospital because of gastrointestinal bleeding and abdominal pain.

The patient had been in his usual state of health until 2 days before presentation, when his parents noted that he began to have intermittent episodes of abdominal pain. During these episodes, some of which woke the patient from sleep, he cried and pulled his legs up toward his chest while lying on his back. His parents reported that they palpated his abdomen during some of the episodes and it felt rigid; they suspected that he might be having discomfort related to excessive intestinal gas. He continued to eat and drink normally without vomiting. The next day, the patient had two bowel movements, and the stools had reddish discoloration. With the first bowel movement, the redness seemed to be present in a small amount and only on the outside of the stool; with the second bowel movement, the amount of redness increased. The patient’s mother attributed the stool discoloration to beet consumption, since bowel movements with reddish stools had also occurred in the past after the patient had eaten beets. Intermittent episodes of apparent abdominal pain continued, and between the episodes, the patient behaved normally. On the morning of presentation, he had a third bowel movement with reddish stools. His parents took him to day care, where he continued to have occasional periods of crying and pain, followed by a bowel movement that appeared to consist almost entirely of blood, including a large clot. After this bowel movement, he was reportedly pale and diaphoretic. The day care provider called the patient’s mother, who picked him up and took him to the emergency department of another hospital.

On examination at the other hospital, the temperature was 36.5°C, the pulse 178 beats per minute, the blood pressure 95/52 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The weight was 9.1 kg. On palpation of the abdomen, there was diffuse tenderness, which was greater on the right side than on the left, and no masses. There were no external anal fissures, and the remainder of the physical examination was normal. Two hours after arrival at the other hospital, the patient passed a dark-red stool that was described as resembling currant jelly. Intravenous normal saline (5 ml per kilogram) was administered, and he was brought by ambulance to the emergency department of this hospital for further evaluation and treatment.

The patient had a history of infantile colic and gastroesophageal reflux, which had previously been treated with ranitidine. He received a low-lactose cow milk–based formula. Pureed fruits and vegetables had recently been introduced into his diet, after which constipation developed, his stools became more firm, and daily bowel movements were associated with straining. He received cholecalciferol, and he had begun using an unspecified over-the-counter teething gel and unspecified homeopathic teething tablets 1 week earlier. Immunizations were current through 4 months of age; vaccines (including the second dose of live, oral human–bovine reassortant pentavalent rotavirus vaccine) had been administered 6 weeks earlier. There were no known allergies. The patient lived with his parents, attended day care, and had no known sick contacts. His parents were from Brazil; he was born in the United States and had not traveled outside the country. There was no family history of bleeding disorders.

On examination, the temperature was 36.3°C, the pulse 160 beats per minute, the blood pressure 98/47 mm Hg, the respiratory rate 32 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. He appeared well. Bowel sounds were present; the abdominal examination was otherwise limited because the patient was crying. The diaper contained melena and a small amount of stool. The remainder of the examination was normal.

Dr. Ruth Lim: Thirty-five minutes after the patient’s arrival in the emergency department, an ultrasound examination of the abdomen was performed. There was no evidence of intussusception, appendicitis, a focal lesion, or abnormally dilated bowel loops. Bowel peristalsis was present.

Table 1.

Laboratory Data.
Dr. Gupta: On examination after ultrasonography, the pulse was 168 beats per minute, and the blood pressure 94/36 mm Hg. The patient appeared pale. The abdomen was soft, without distention, tenderness, or masses, and bowel sounds were present. Results of the physical examination were otherwise unchanged. Blood levels of electrolytes, glucose, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, and C-reactive protein were normal, as were the anion gap, platelet count, red-cell indexes, and results of renal-function tests. The results of other laboratory tests are shown in Table 1. Packed red cells were transfused, and pantoprazole and famotidine were administered intravenously.

A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:            A 6-month-old boy was seen in the emergency department of this hospital because of gastrointestinal bleeding and abdominal pain.

The patient had been in his usual state of health until 2 days before presentation, when his parents noted that he began to have intermittent episodes of abdominal pain. During these episodes, some of which woke the patient from sleep, he cried and pulled his legs up toward his chest while lying on his back. His parents reported that they palpated his abdomen during some of the episodes and it felt rigid; they suspected that he might be having discomfort related to excessive intestinal gas. He continued to eat and drink normally without vomiting. The next day, the patient had two bowel movements, and the stools had reddish discoloration. With the first bowel movement, the redness seemed to be present in a small amount and only on the outside of the stool; with the second bowel movement, the amount of redness increased. The patient’s mother attributed the stool discoloration to beet consumption, since bowel movements with reddish stools had also occurred in the past after the patient had eaten beets. Intermittent episodes of apparent abdominal pain continued, and between the episodes, the patient behaved normally. On the morning of presentation, he had a third bowel movement with reddish stools. His parents took him to day care, where he continued to have occasional periods of crying and pain, followed by a bowel movement that appeared to consist almost entirely of blood, including a large clot. After this bowel movement, he was reportedly pale and diaphoretic. The day care provider called the patient’s mother, who picked him up and took him to the emergency department of another hospital.

On examination at the other hospital, the temperature was 36.5°C, the pulse 178 beats per minute, the blood pressure 95/52 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The weight was 9.1 kg. On palpation of the abdomen, there was diffuse tenderness, which was greater on the right side than on the left, and no masses. There were no external anal fissures, and the remainder of the physical examination was normal. Two hours after arrival at the other hospital, the patient passed a dark-red stool that was described as resembling currant jelly. Intravenous normal saline (5 ml per kilogram) was administered, and he was brought by ambulance to the emergency department of this hospital for further evaluation and treatment.

The patient had a history of infantile colic and gastroesophageal reflux, which had previously been treated with ranitidine. He received a low-lactose cow milk–based formula. Pureed fruits and vegetables had recently been introduced into his diet, after which constipation developed, his stools became more firm, and daily bowel movements were associated with straining. He received cholecalciferol, and he had begun using an unspecified over-the-counter teething gel and unspecified homeopathic teething tablets 1 week earlier. Immunizations were current through 4 months of age; vaccines (including the second dose of live, oral human–bovine reassortant pentavalent rotavirus vaccine) had been administered 6 weeks earlier. There were no known allergies. The patient lived with his parents, attended day care, and had no known sick contacts. His parents were from Brazil; he was born in the United States and had not traveled outside the country. There was no family history of bleeding disorders.

On examination, the temperature was 36.3°C, the pulse 160 beats per minute, the blood pressure 98/47 mm Hg, the respiratory rate 32 breaths per minute, and the oxygen saturation 99% while the patient was breathing ambient air. He appeared well. Bowel sounds were present; the abdominal examination was otherwise limited because the patient was crying. The diaper contained melena and a small amount of stool. The remainder of the examination was normal.

Dr. Ruth Lim: Thirty-five minutes after the patient’s arrival in the emergency department, an ultrasound examination of the abdomen was performed. There was no evidence of intussusception, appendicitis, a focal lesion, or abnormally dilated bowel loops. Bowel peristalsis was present.

Table 1.

Laboratory Data.
Dr. Gupta: On examination after ultrasonography, the pulse was 168 beats per minute, and the blood pressure 94/36 mm Hg. The patient appeared pale. The abdomen was soft, without distention, tenderness, or masses, and bowel sounds were present. Results of the physical examination were otherwise unchanged. Blood levels of electrolytes, glucose, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, and C-reactive protein were normal, as were the anion gap, platelet count, red-cell indexes, and results of renal-function tests. The results of other laboratory tests are shown in Table 1. Packed red cells were transfused, and pantoprazole and famotidine were administered intravenously.

A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Meckel's Diverticulum. The patient's symptoms of abdominal pain, rigid abdomen, and gastrointestinal bleeding are consistent with Meckel's Diverticulum, a congenital abnormality of the intestine. The presence of a \""currant jelly\"" stool is also a common symptom of this condition, as it indicates the presence of blood and mucus in the stool. The patient's age is also consistent with the typical age of presentation for Meckel's Diverticulum, which is most commonly diagnosed in children under the age of 2. The negative ultrasound results rule out other potential causes of the patient's symptoms, such as intussusception or appendicitis.""
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        ""content"": ""The patient's symptoms of intermittent abdominal pain, rigid abdomen, and bloody stools are indicative of a gastrointestinal issue. The description of the stool as \""currant jelly\"" is a classic sign of intussusception, a condition in which one part of the intestine telescopes into another part. However, an ultrasound examination did not show evidence of intussusception. The patient's history of colic and gastroesophageal reflux, as well as recent changes in diet and bowel habits, suggest a possible gastrointestinal bleed. The patient's pale appearance and the laboratory results showing a low hemoglobin level and a high reticulocyte count indicate that the patient is anemic and that the body is responding to this by producing more red blood cells. This, along with the presence of melena (dark, tarry stools due to digested blood) in the diaper, suggests that the patient has been losing blood through the gastrointestinal tract. \n\nDiagnosis: Gastrointestinal bleeding.""
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        ""content"": ""The patient is a 6-month-old boy presenting with gastrointestinal bleeding and abdominal pain. The differential diagnosis for this patient includes gastroenteritis, food allergy, Meckel's diverticulum, intussusception, and hemorrhagic disease of the newborn. The patient's history of colic and gastroesophageal reflux, as well as the recent introduction of pureed fruits and vegetables into his diet, could suggest a food allergy or intolerance. However, the presence of blood in the stool is not typical for these conditions. Gastroenteritis could also cause abdominal pain and bloody stools, but the patient has no other symptoms such as vomiting or fever. Intussusception could cause abdominal pain and bloody stools, but this was ruled out by the ultrasound examination. Meckel's diverticulum, a congenital abnormality of the small intestine, could cause painless rectal bleeding, but the patient's abdominal pain makes this less likely. Hemorrhagic disease of the newborn, a bleeding disorder caused by vitamin K deficiency, could cause bloody stools, but this is unlikely given the patient's age and the absence of other bleeding symptoms. The patient's symptoms are most consistent with a gastrointestinal bleed, possibly due to a peptic ulcer or gastritis. The administration of pantoprazole and famotidine, both of which reduce stomach acid, supports this diagnosis.\n\nDiagnosis: Gastrointestinal bleed due to peptic ulcer or gastritis.""
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10.1056/NEJMcpc1616024,"Case 9-2017 — A 27-Year-Old Woman with Nausea, Vomiting, Confusion, and Hyponatremia",,Primary adrenal insufficiency (Addison’s disease).,Primary adrenal insufficiency.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 A 27-year-old woman was admitted to this hospital because of nausea, vomiting, confusion, and hyponatremia.

The patient had been well until 1 week before admission, when she had nausea and nonbloody, nonbilious emesis. She did not seek medical care, and her symptoms resolved after several hours. Two days before admission, she had nausea and several episodes of nonbloody, nonbilious emesis in the evening, after she had eaten seafood. The day before admission, she had recurrent vomiting associated with eating but was able to drink large amounts of water. Earlier that day, she had normal interaction with friends and participated in sightseeing activities, including long-distance walking. Early in the evening, she was noted to be slightly confused. Later in the evening, her friend had difficulty arousing her from sleep, and she was not able to follow directions or walk. She was carried to a car by two of her traveling companions and taken to the emergency department of another hospital for evaluation.

On examination, the temperature was 36.1°C, the blood pressure 94/64 mm Hg, the pulse 100 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She was lethargic and did not respond to questions or commands. Her speech was incoherent, and she cried intermittently. The pupils were 8 mm in diameter and responsive to light. She moved her arms and legs nonpurposefully. The remainder of the examination was normal. On repeat measurement, the blood pressure was 73/54 mm Hg. Intravenous access was obtained, and 700 ml of normal saline was administered intravenously before the laboratory test results were received.

The blood level of sodium was 104 mmol per liter (reference range, 135 to 145), potassium 5.1 mmol per liter (reference range, 3.5 to 5.0), chloride 74 mmol per liter (reference range, 98 to 107), carbon dioxide 19 mmol per liter (reference range, 24 to 32), and glucose 114 mg per deciliter (6.3 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]) and the anion gap was 11 mmol per liter (reference range, 3 to 15). The blood level of aspartate aminotransferase was 37 U per liter (reference range, 10 to 32), and alanine aminotransferase 37 U per liter (reference range, 7 to 35). The blood levels of total protein, albumin, total bilirubin, and lipase were normal, as were the results of renal-function tests. A urine test for human chorionic gonadotropin and a urine drug screen were negative. The blood level of salicylate was less than 0.2 mg per deciliter (0.01 mmol per liter; reference range, 2.8 to 20.0 mg per deciliter [0.20 to 1.44 mmol per liter]), and acetaminophen 0 _g per milliliter. Intensive care was not available at the other hospital, and the patient was transferred to this hospital by helicopter. During the flight, the patient was agitated and unable to lie still. Ketamine was administered, along with normal saline and hypertonic saline.

On evaluation in the emergency department of this hospital, the patient was unable to answer questions, and further history was obtained from her family. She was healthy and used an etonogestrel implant. She was a graduate student, resided in the southern United States, and was visiting New England with friends. She drank alcohol occasionally and did not smoke tobacco or use over-the-counter medications. Her mother had had breast cancer, but there was no family history of autoimmune disease.

On examination, the temperature was 36.7°C, the blood pressure 102/57 mm Hg, the pulse 92 beats per minute, the respiratory rate 12 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She was somnolent and did not respond to commands, but she opened her eyes and withdrew in response to painful stimuli. The pupils were round, equal, and reactive to light. The mucous membranes were moist. The skin turgor was normal. The first and second heart sounds were normal, without murmurs. The breath sounds were normal in both lungs, without wheezing or rhonchi. Bowel sounds were present, and the abdomen was soft, nondistended, and nontender on palpation. The edge of the liver was not palpable. There was no splenomegaly. The arms and legs had no edema. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Additional laboratory studies were performed, and the results are shown in Table 1. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed no acute intracranial hemorrhage, infarction, or intracranial mass lesions. Chest radiography revealed low lung volumes without focal consolidation or pulmonary edema, a normal cardiac silhouette, and no pleural effusions.

The patient was admitted to the intensive care unit (ICU), and diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:             A 27-year-old woman was admitted to this hospital because of nausea, vomiting, confusion, and hyponatremia.

The patient had been well until 1 week before admission, when she had nausea and nonbloody, nonbilious emesis. She did not seek medical care, and her symptoms resolved after several hours. Two days before admission, she had nausea and several episodes of nonbloody, nonbilious emesis in the evening, after she had eaten seafood. The day before admission, she had recurrent vomiting associated with eating but was able to drink large amounts of water. Earlier that day, she had normal interaction with friends and participated in sightseeing activities, including long-distance walking. Early in the evening, she was noted to be slightly confused. Later in the evening, her friend had difficulty arousing her from sleep, and she was not able to follow directions or walk. She was carried to a car by two of her traveling companions and taken to the emergency department of another hospital for evaluation.

On examination, the temperature was 36.1°C, the blood pressure 94/64 mm Hg, the pulse 100 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She was lethargic and did not respond to questions or commands. Her speech was incoherent, and she cried intermittently. The pupils were 8 mm in diameter and responsive to light. She moved her arms and legs nonpurposefully. The remainder of the examination was normal. On repeat measurement, the blood pressure was 73/54 mm Hg. Intravenous access was obtained, and 700 ml of normal saline was administered intravenously before the laboratory test results were received.

The blood level of sodium was 104 mmol per liter (reference range, 135 to 145), potassium 5.1 mmol per liter (reference range, 3.5 to 5.0), chloride 74 mmol per liter (reference range, 98 to 107), carbon dioxide 19 mmol per liter (reference range, 24 to 32), and glucose 114 mg per deciliter (6.3 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]) and the anion gap was 11 mmol per liter (reference range, 3 to 15). The blood level of aspartate aminotransferase was 37 U per liter (reference range, 10 to 32), and alanine aminotransferase 37 U per liter (reference range, 7 to 35). The blood levels of total protein, albumin, total bilirubin, and lipase were normal, as were the results of renal-function tests. A urine test for human chorionic gonadotropin and a urine drug screen were negative. The blood level of salicylate was less than 0.2 mg per deciliter (0.01 mmol per liter; reference range, 2.8 to 20.0 mg per deciliter [0.20 to 1.44 mmol per liter]), and acetaminophen 0 _g per milliliter. Intensive care was not available at the other hospital, and the patient was transferred to this hospital by helicopter. During the flight, the patient was agitated and unable to lie still. Ketamine was administered, along with normal saline and hypertonic saline.

On evaluation in the emergency department of this hospital, the patient was unable to answer questions, and further history was obtained from her family. She was healthy and used an etonogestrel implant. She was a graduate student, resided in the southern United States, and was visiting New England with friends. She drank alcohol occasionally and did not smoke tobacco or use over-the-counter medications. Her mother had had breast cancer, but there was no family history of autoimmune disease.

On examination, the temperature was 36.7°C, the blood pressure 102/57 mm Hg, the pulse 92 beats per minute, the respiratory rate 12 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. She was somnolent and did not respond to commands, but she opened her eyes and withdrew in response to painful stimuli. The pupils were round, equal, and reactive to light. The mucous membranes were moist. The skin turgor was normal. The first and second heart sounds were normal, without murmurs. The breath sounds were normal in both lungs, without wheezing or rhonchi. Bowel sounds were present, and the abdomen was soft, nondistended, and nontender on palpation. The edge of the liver was not palpable. There was no splenomegaly. The arms and legs had no edema. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Additional laboratory studies were performed, and the results are shown in Table 1. Computed tomography (CT) of the head, performed without the administration of intravenous contrast material, revealed no acute intracranial hemorrhage, infarction, or intracranial mass lesions. Chest radiography revealed low lung volumes without focal consolidation or pulmonary edema, a normal cardiac silhouette, and no pleural effusions.

The patient was admitted to the intensive care unit (ICU), and diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Psychogenic polydipsia\n\nThe patient's symptoms of nausea, vomiting, and confusion, along with her hyponatremia, suggest a disorder related to water balance. The fact that she was able to drink large amounts of water the day before admission suggests that she may have been excessively thirsty, which is a symptom of diabetes insipidus and psychogenic polydipsia. However, her urine osmolality was high, which rules out diabetes insipidus, as this condition would cause the urine to be dilute. This leaves psychogenic polydipsia, a condition where patients have a compulsion to drink excessive amounts of water, as the most likely diagnosis. This condition can lead to water intoxication and hyponatremia, which can cause the symptoms the patient is experiencing.""
      },
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        ""content"": ""The patient's symptoms of nausea, vomiting, confusion, and hyponatremia, along with her history of drinking large amounts of water, suggest a diagnosis of water intoxication, also known as water poisoning or overhydration. This condition occurs when someone drinks so much water that their kidneys can't excrete the excess water. As a result, the water dilutes electrolytes in the blood, particularly sodium. When sodium levels fall below 135 mmol/L, it's called hyponatremia. Sodium helps balance fluids between the inside and outside of cells. When sodium levels drop due to excess water consumption, fluids shifts from the outside to the inside of cells, causing them to swell. When this happens in the brain, it can be life-threatening. The patient's sodium level was significantly below the normal range at 104 mmol per liter, which is consistent with severe hyponatremia. \n\nDiagnosis: Water intoxication (overhydration) leading to severe hyponatremia.""
      },
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}",Water intoxication (overhydration) leading to severe hyponatremia,N,"{
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        ""content"": ""The patient is a young woman presenting with nausea, vomiting, confusion, and hyponatremia. The differential diagnosis for this patient includes syndrome of inappropriate antidiuretic hormone secretion (SIADH), cerebral salt-wasting syndrome, Addison's disease, and psychogenic polydipsia. The patient's symptoms of nausea and vomiting could be due to Addison's disease, but the absence of hyperpigmentation, hypotension, and hyperkalemia makes this diagnosis less likely. The patient's confusion could be due to cerebral salt-wasting syndrome, but the absence of recent head trauma or surgery makes this diagnosis less likely. The patient's hyponatremia could be due to SIADH, but the absence of lung disease, cancer, or medications known to cause SIADH makes this diagnosis less likely. The patient's history of drinking large amounts of water and the absence of edema or signs of volume overload suggest psychogenic polydipsia, a condition characterized by excessive water intake that can lead to hyponatremia. \n\nDiagnosis: Psychogenic polydipsia.""
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}",Psychogenic polydipsia,N
10.1056/NEJMcpc1516450,Case 8-2017 — A 39-Year-Old Zimbabwean Man with a Severe Headache,,Cryptococcal meningitis in a patient with chronic human immunodeficiency virus infection.,Cryptococcal meningitis in a patient with chronic human immunodeficiency virus infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:         A 39-year-old man was admitted to a large, urban tertiary-care hospital in Zimbabwe (where a physician affiliated with this hospital works) because of a severe headache.

The patient had been in his usual health until approximately 1 month before admission, when headaches developed. The headaches were initially intermittent and then gradually became persistent, with increasing severity. The patient took paracetamol (acetaminophen), but his condition did not improve. On the evening of admission, one episode of emesis occurred. On evaluation in the emergency department, the patient reported a severe frontal headache, neck pain, and photophobia, with no hearing loss, visual symptoms, seizures, or new rashes. He had no recent trauma, weight loss, night sweats, cough, or shortness of breath.

During the month before admission, the patient had received a diagnosis of non–insulin-dependent diabetes mellitus (NIDDM), for which metformin and glibenclamide were administered. He was otherwise well. He reported that he had not been tested for human immunodeficiency virus (HIV) in the past, and he was taking no other medications. He lived with his wife and children in a suburban area and worked as a long-distance truck driver. He had traveled to Zambia 2 weeks before admission. He had stopped drinking alcohol approximately 2 years before admission and had never smoked tobacco. His sister had NIDDM, and his children were healthy.

Table 1.

Laboratory Data.
On examination, the temperature was 36.8°C, the blood pressure 125/78 mm Hg, the pulse 53 beats per minute, and the respiratory rate 18 breaths per minute. The patient was alert and fully oriented, with a normal level of consciousness. His neck was stiff, with nuchal rigidity, and the remainder of the examination was normal. A peripheral-blood smear and a rapid test for malaria antigen were negative for malaria. A lumbar puncture was performed without additional imaging of the brain, since the patient had no focal neurologic signs. The opening pressure was 25 cm of water (normal, <20). Results of the cerebrospinal fluid (CSF) analysis and other laboratory test results are shown in Table 1. Penicillin and chloramphenicol were administered, and diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:             A 39-year-old man was admitted to a large, urban tertiary-care hospital in Zimbabwe (where a physician affiliated with this hospital works) because of a severe headache.

The patient had been in his usual health until approximately 1 month before admission, when headaches developed. The headaches were initially intermittent and then gradually became persistent, with increasing severity. The patient took paracetamol (acetaminophen), but his condition did not improve. On the evening of admission, one episode of emesis occurred. On evaluation in the emergency department, the patient reported a severe frontal headache, neck pain, and photophobia, with no hearing loss, visual symptoms, seizures, or new rashes. He had no recent trauma, weight loss, night sweats, cough, or shortness of breath.

During the month before admission, the patient had received a diagnosis of non–insulin-dependent diabetes mellitus (NIDDM), for which metformin and glibenclamide were administered. He was otherwise well. He reported that he had not been tested for human immunodeficiency virus (HIV) in the past, and he was taking no other medications. He lived with his wife and children in a suburban area and worked as a long-distance truck driver. He had traveled to Zambia 2 weeks before admission. He had stopped drinking alcohol approximately 2 years before admission and had never smoked tobacco. His sister had NIDDM, and his children were healthy.

Table 1.

Laboratory Data.
On examination, the temperature was 36.8°C, the blood pressure 125/78 mm Hg, the pulse 53 beats per minute, and the respiratory rate 18 breaths per minute. The patient was alert and fully oriented, with a normal level of consciousness. His neck was stiff, with nuchal rigidity, and the remainder of the examination was normal. A peripheral-blood smear and a rapid test for malaria antigen were negative for malaria. A lumbar puncture was performed without additional imaging of the brain, since the patient had no focal neurologic signs. The opening pressure was 25 cm of water (normal, <20). Results of the cerebrospinal fluid (CSF) analysis and other laboratory test results are shown in Table 1. Penicillin and chloramphenicol were administered, and diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Cryptococcal meningitis\n\nThe patient's symptoms of severe headache, neck pain, and photophobia, along with the elevated opening pressure and the CSF analysis results, are indicative of meningitis. The patient's occupation as a long-distance truck driver could have exposed him to the Cryptococcus fungus, which is found in soil and bird droppings and can cause meningitis. The patient's recent diagnosis of diabetes could have compromised his immune system, making him more susceptible to infection. The negative malaria tests rule out that disease. The administration of penicillin and chloramphenicol, antibiotics, would not be effective against a fungal infection, further supporting the diagnosis of cryptococcal meningitis.""
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        ""content"": ""The patient's symptoms of severe headache, neck pain, and photophobia, along with the finding of nuchal rigidity and elevated opening pressure on lumbar puncture, are suggestive of meningitis. The patient's CSF analysis shows a lymphocytic predominance, which is more typical of viral or tuberculous meningitis than bacterial meningitis. Given the patient's location in Zimbabwe and occupation as a long-distance truck driver, tuberculosis is a likely possibility. The patient's newly diagnosed diabetes could also make him more susceptible to infections like tuberculosis. \n\nDiagnosis: Tuberculous meningitis.""
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}",Tuberculous meningitis,N,"{
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  ""choices"": [
    {
      ""index"": 0,
      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient is a 39-year-old man presenting with a severe headache, neck pain, and photophobia. He has no history of trauma, weight loss, night sweats, cough, or shortness of breath. He was recently diagnosed with non-insulin-dependent diabetes mellitus. He is a long-distance truck driver and recently traveled to Zambia. His examination reveals nuchal rigidity but no other focal neurologic signs. His CSF analysis shows an elevated opening pressure and a lymphocytic pleocytosis. \n\nThe differential diagnosis for this patient includes meningitis (bacterial, viral, or fungal), subarachnoid hemorrhage, and intracranial mass (such as a tumor or abscess). The patient's lack of focal neurologic signs makes an intracranial mass less likely. His CSF analysis does not show xanthochromia or a high red blood cell count, which would be expected in a subarachnoid hemorrhage, making this diagnosis less likely. The patient's CSF analysis shows a lymphocytic pleocytosis, which is more consistent with viral or fungal meningitis than bacterial meningitis. Given the patient's recent travel to Zambia, a region endemic for fungal infections such as cryptococcal meningitis, especially in the setting of HIV, this diagnosis should be considered. \n\nDiagnosis: Cryptococcal meningitis.""
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}",Cryptococcal meningitis,Y
10.1056/NEJMcpc1613462,Case 7-2017 — A 73-Year-Old Man with Confusion and Recurrent Epistaxis,,"ascular malformations in the liver, stomach, esophagus, and lungs that are consistent with hereditary hemorrhagic telangiectasia, complicated by massive gastrointestinal hemorrhage.",Hepatic encephalopathy in a patient with hereditary hemorrhagic telangiectasia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 73-year-old man with multiple chronic medical illnesses was admitted to this hospital because of confusion and irritability.

Two days before this admission, increasing weakness, lethargy, chills, and diarrhea developed. The patient became less responsive to his family and increasingly irritable and confused. He stopped taking his medications. On the day of admission, his oral intake was 500 ml of liquid. His family reported that he was in an “almost catatonic” state; he was unable to arise from bed, had recurrent epistaxis, and reported pain in his chest and left arm. He was brought to the emergency department of this hospital.

The patient had been in poor health, with a recent diagnosis of atypical pneumonia, which was treated with levofloxacin. He had a history of diabetes mellitus, atrial fibrillation, coronary artery disease, diastolic heart failure, and pulmonary hypertension. Cardiac evaluations that had been performed over the previous decade had revealed an exudative pericardial effusion that had spontaneously resolved, as well as heart failure predominantly on the right side (left ventricular ejection fraction, 69%; pulmonary arterial systolic pressure, 61 mm Hg). A biopsy of the right side of the heart did not reveal a cause of the heart failure. The patient had had recurrent epistaxis since childhood, and it had recently worsened. Additional medical history included hyperlipidemia, pancytopenia, obstructive sleep apnea, gastroesophageal reflux disease, and headaches; there was also a possible history of an arteriovenous malformation of the brain, which had been noted on an imaging study obtained 20 years earlier but had not been confirmed on magnetic resonance imaging (MRI) performed at this hospital 7 years before this admission. He had undergone excision of a basal-cell carcinoma and an appendectomy.

One month before this admission, the patient had been admitted to this hospital because of acute confusion and worsening edema. During that admission, ultrasonography of the right upper quadrant was performed.

Figure 1.

Ultrasound Images of the Right Upper Quadrant.
Dr. Shaunagh McDermott: An image of the right lower lobe of the liver showed a communication between the right portal vein and the right hepatic vein, a finding consistent with a hepatic venovenous malformation with portosystemic shunting (Figure 1).

Dr. Greenwald: A diagnosis of hepatic encephalopathy was made. The confusion improved after the initiation of treatment with lactulose and rifaximin.

On the current admission, medications included warfarin, metoprolol, simvastatin, furosemide, spironolactone, potassium chloride, lactulose, rifaximin, ferrous sulfate, glipizide, metformin, omeprazole, and, owing to enrollment in a clinical trial investigating therapies for pulmonary hypertension, either sildenafil or placebo. The patient had had adverse reactions to azithromycin, lansoprazole, and metolazone. He lived with his wife and was retired from a position in higher education. He did not smoke tobacco, drink alcohol, or use illicit drugs. His parents had died when they were in their 70s; his father had had heart disease, and his mother had had a stroke. His mother and his daughter had a history of recurrent epistaxis and of easy bleeding.

On examination, the patient was somnolent but easily roused by vocal stimulation. He was oriented and cooperative, with waxing and waning attention, and he was uncertain about why he was in the hospital. The temperature was 37.4°C, the blood pressure 141/61 mm Hg, the pulse 103 beats per minute, the respiratory rate 28 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. The mucous membranes were dry, and dried blood was noted around the nares. There were multiple telangiectasias on the face, lips, and torso, and there were nonblanching cherry angiomas on the chest. The heart sounds were irregularly irregular; the first and second sounds were otherwise normal. The lungs were clear bilaterally. There was mild tenderness in the right upper quadrant, with no rebound or guarding. Bowel sounds were present. There was no abdominal distention, and the edge of the liver was palpable 2 cm below the right costal margin. Testing for Murphy’s sign was negative. No rectal masses were detected on palpation; the stool was brown, with trace blood. There was no asterixis. The legs were dark and discolored, a finding consistent with chronic venous insufficiency. The remainder of the general and neurologic examinations was normal.

Table 1.

Laboratory Data.
Blood levels of total and direct bilirubin, total protein, albumin, globulin, phosphorus, magnesium, calcium, aspartate aminotransferase, alanine aminotransferase, amylase, lipase, and lactic acid were normal, as were levels of vitamin B12 and folate, which had been obtained 1 week earlier; other laboratory test results are shown in Table 1. Urinalysis revealed clear yellow fluid, with a specific gravity of 1.020, a pH of 5.5, and trace blood; the urine sediment showed 0 to 2 white cells and 0 to 2 red cells per high-power field, 20 to 100 hyaline casts and 0 to 2 granular casts per low-power field, and mucin. Screening of the urine for toxins was negative. An electrocardiogram revealed atrial fibrillation, frequent premature ventricular contractions, ST-segment depression of at least 1 mm in leads II, III, and aVF, and downsloping ST-segment depression of 2 mm in lead V6.

Figure 2.

CT Scan of the Abdomen.
Dr. McDermott: A radiograph of the chest showed evidence of persistent interstitial edema and focal opacities in both lower lobes; these findings could represent alveolar edema, superimposed pneumonia, or aspiration. Computed tomography (CT) of the abdomen, performed with the administration of oral contrast material, revealed nonspecific pneumatosis of the ascending colon to the level of the hepatic flexure, without associated portal venous gas or other inflammatory changes. Cholelithiasis, atherosclerotic disease of the aorta and mesenteric vessels, and cardiomegaly were also present (Figure 2).

Dr. Greenwald: Intravenous normal saline, vancomycin, cefepime, and oral potassium chloride were administered, and the patient was admitted to this hospital. On his arrival in the inpatient unit, the dose of rifaximin was increased, warfarin and furosemide were discontinued, and lactulose and other outpatient medications were resumed. On evaluation the next morning, approximately 12 hours after his presentation, the patient was less confused.

Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Hereditary Hemorrhagic Telangiectasia (HHT)\n\nThe patient's history of recurrent epistaxis since childhood, multiple telangiectasias on the face, lips, and torso, and nonblanching cherry angiomas on the chest are indicative of HHT. The patient's mother and daughter also had a history of recurrent epistaxis and easy bleeding, suggesting a genetic component. The presence of a hepatic venovenous malformation with portosystemic shunting, as seen on the ultrasound, is also consistent with HHT. The patient's confusion and altered mental status can be explained by hepatic encephalopathy, which can occur in HHT due to portosystemic shunting.""
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        ""content"": ""The patient's history of recurrent epistaxis, telangiectasias on physical examination, and a family history of recurrent epistaxis and easy bleeding suggest a diagnosis of hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome. This is a genetic disorder that leads to abnormal blood vessel formation in the skin, mucous membranes, and often in organs such as the lungs, liver, and brain. The patient's hepatic venovenous malformation with portosystemic shunting could be a manifestation of HHT, as arteriovenous malformations are common in this disease. The patient's confusion could be due to hepatic encephalopathy, which can occur in HHT due to portosystemic shunting. \n\nDiagnosis: Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu syndrome)""
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        ""content"": ""A 45-year-old woman was admitted to the hospital because of a 2-week history of fever, fatigue, and a rash. The patient had been well until 2 weeks before this admission, when she developed a fever, fatigue, and a rash on her trunk and extremities. She also reported a 5-pound weight loss over the past month. She had no history of recent travel, sick contacts, or changes in her diet. She had no known drug allergies and was not taking any medications. She had a history of hypertension, for which she was not taking medication. She had no history of smoking, alcohol use, or illicit drug use. She had no family history of autoimmune diseases or malignancies. On physical examination, the patient appeared ill. Her temperature was 38.7\u00b0C, blood pressure was 130/80 mm Hg, pulse rate was 110 beats per minute, and respiratory rate was 20 breaths per minute. She had a diffuse, maculopapular rash on her trunk and extremities. There was no lymphadenopathy or hepatosplenomegaly. The remainder of the examination was normal. Laboratory studies showed a white-cell count of 11,000 per cubic millimeter, with 70% neutrophils, 20% lymphocytes, and 10% monocytes. The hemoglobin level was 10.5 g per deciliter, and the platelet count was 150,000 per cubic millimeter. The erythrocyte sedimentation rate was 50 mm per hour, and the C-reactive protein level was 3.0 mg per deciliter. The serum creatinine level was 1.0 mg per deciliter, and the alanine aminotransferase and aspartate aminotransferase levels were within normal limits. The serum albumin level was 3.0 g per deciliter. Tests for antinuclear antibodies, anti-double-stranded DNA antibodies, and anti-neutrophil cytoplasmic antibodies were negative. A chest radiograph showed no abnormalities. A skin biopsy was performed.\n\nRationale:\nThe patient presents with fever, fatigue, rash, and weight loss. The differential diagnosis includes infection, malignancy, and autoimmune disease. Given the patient's age, malignancy such as lymphoma should be considered. However, the lack of lymphadenopathy or hepatosplenomegaly makes this less likely. Infection is also a possibility, but the patient has no history of recent travel, sick contacts, or changes in diet, and her white blood cell count is not significantly elevated. Autoimmune disease is another possibility, but tests for antinuclear antibodies, anti-double-stranded DNA antibodies, and anti-neutrophil cytoplasmic antibodies were negative, making conditions such as lupus or vasculitis less likely. The patient's rash, fever, and weight loss could be consistent with Still's disease, an inflammatory condition characterized by high fevers, rash, and joint pain. However, the patient does not report joint pain. The skin biopsy may provide further information to help narrow the differential diagnosis.\n\nDiagnosis:\nThe diagnosis is currently unclear and pending further investigation, such as the results of the skin biopsy.""
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}","he diagnosis is currently unclear and pending further investigation, such as the results of the skin biopsy",N
10.1056/NEJMcpc1613461,"Case 6-2017 — A 57-Year-Old Woman with Fatigue, Sweats, Weight Loss, Headache, and Skin Lesions",,IgG4-related vasculitis.,IgG4-related vasculitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                A 57-year-old woman was seen in the outpatient rheumatology clinic of this hospital because of fatigue, night sweats, weight loss, headache, diffuse abdominal pain, and skin lesions.

Table 1.

Laboratory Data.
The patient had been well until approximately 24 months before this evaluation, when a dry, nonproductive cough developed. Results of laboratory testing, which was performed at another hospital, are shown in Table 1.

Twenty-one months before this evaluation, when the patient was seen by her physician at another clinic, she reported persistent cough, decreased appetite, and moderate but poorly localized abdominal pain. On examination, her weight was 108.9 kg (decreased from her baseline weight of 122.5 kg 5 months earlier). A proton-pump inhibitor was administered. During the following month, fatigue and myalgias occurred, followed by the appearance of painless “red dots” around her ankles. Evaluation of a skin-biopsy specimen reportedly revealed findings consistent with early pigmented purpuric dermatosis. Blood tests revealed peripheral eosinophilia.

Twenty months before this evaluation, the patient was seen at the other hospital because of persistent cough; laboratory test results are shown in Table 1. A chest radiograph was reportedly normal. Computed tomography (CT) of the chest, abdomen, and pelvis, performed without the administration of contrast material, revealed mild, diffuse bronchial-wall thickening, a finding suggestive of chronic inflammation. Mildly enlarged lymph nodes were present in the paracardiac region, porta hepatis, mesentery, and retroperitoneum.

During the following year, multiple evaluations by consultants in allergy, rheumatology, hematology–oncology, endocrinology, and gastroenterology were performed. Nineteen months before this evaluation, esophagogastroduodenoscopy was performed, and pathological examination of biopsy specimens from the gastric antrum revealed mild chronic and focally active gastritis. Immunohistochemical staining for Helicobacter pylori was negative, and the small-bowel villi were normal.

Dr. Amita Sharma: Magnetic resonance imaging of the abdomen, performed at the other hospital 18 months before this evaluation, revealed enlarged periportal lymph nodes. No focal lesions were seen in the liver, pancreas, kidneys, spleen, or adrenal glands. There was mild splenomegaly. The pancreas was not enlarged. Sixteen months before this evaluation, CT of the chest, abdomen, and pelvis, performed after the intravenous administration of contrast material, reportedly revealed mild bronchial-wall thickening, lymphadenopathy in the axillae (with the largest node, in the right axilla, measuring 2.3 cm by 1.3 cm), an enlarged right epicardial lymph node (measuring 1.5 cm by 1.1 cm), and enlarged nodes in the portacaval, peripancreatic, and mesenteric regions (with the largest node, in the porta hepatis, measuring 4.2 cm by 2.9 cm).

Dr. Heaton: One month later, pathological examination of a right axillary lymph node revealed preserved architecture. Follicular and paracortical hyperplasia was present, along with a polytypic plasmacytosis. Immunostaining for human herpesvirus 8 (HHV-8) DNA was negative. The findings were consistent with reactive lymphadenopathy; no evidence of hematologic cancer was identified. Therapeutic trials of oral metoclopramide, cetirizine, omeprazole, and budesonide; fluticasone nasal spray; and inhaled fluticasone–salmeterol resulted in no improvement. The patient continued to lose weight.

Dr. Sharma: Thirteen months before this evaluation, 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET), performed at the other hospital, revealed FDG-avid lymph nodes in the axillae, the paracardial region, and the region of the right internal thoracic artery. The liver and spleen were enlarged and showed diffuse FDG uptake.

Dr. Heaton: Examination of a bone marrow–biopsy specimen and bone marrow aspirate revealed hypercellular bone marrow with maturing trilineage hematopoiesis, increased eosinophils, megakaryocytes, and polyclonal plasma cells, findings that are consistent with a reactive process. Biopsy of the liver was performed to investigate the hepatosplenomegaly and the FDG uptake in the liver and spleen. Pathological examination of a core needle–biopsy specimen of the liver revealed moderate-to-severe portal, periportal, and lobular inflammation that was predominantly composed of plasma cells (with polytypic expression of kappa and lambda light chains on immunohistochemical staining), with occasional eosinophils. Bile-duct proliferation, focal damage, intraepithelial lymphocytes, and scattered apoptotic hepatocytes were seen, and trichrome staining highlighted the presence of sinusoidal fibrosis. A stain for iron deposition was negative. The findings were thought to be consistent with an overlap syndrome of autoimmune hepatitis and focal sclerosing cholangitis. Treatment with prednisone was begun but was discontinued by the patient for unspecified reasons. Azathioprine therapy was also begun at this time. A decrease in abdominal pain and fatigue was reported.

Figure 1.

18F-Fluorodeoxyglucose (FDG) Positron-Emission Tomographic (PET) Scan.
Dr. Sharma: Seven months before this evaluation, an FDG-PET examination with CT for attenuation correction was performed at the other hospital (Figure 1). Splenomegaly was present, and stably enlarged FDG-avid lymph nodes were seen in the axillae, the region of the internal thoracic artery, the right paracardiac region, and the retroperitoneal, iliac, and inguinal regions. There was no hilar lymphadenopathy. There was diffuse, mild, smooth bronchial-wall thickening. No pulmonary nodules or air-space opacities were present.

Dr. Heaton: One month later, an inguinal lymph node was excised. Pathological examination revealed follicular hyperplasia and a polytypic plasmacytosis of the medulla and sinusoidal regions. On immunohistochemical studies for IgG and IgG4, a small fraction of the plasma cells were immunoreactive for IgG4. Four months before this evaluation, the patient was evaluated for a nonproductive cough, severe fatigue, weight loss, anorexia, abdominal pain, nausea, vomiting, joint pain, diffuse aches, swelling of the right knee, and night sweats. Further weight loss (to 88.5 kg from her baseline weight of 122.5 kg) was noted. Additional laboratory test results are shown in Table 1. Two months before this evaluation, severe and increasing bitemporal headache developed. The patient was referred to the rheumatology clinic of this hospital.

On evaluation at this hospital, the patient reported daily headaches and pain in her jaw when she chewed food. She did not report dry eyes or dry mouth. She had hypertension, anemia, and chronic left-knee pain after an injury that had occurred 6 years previously; she had undergone a hysterectomy and trigger-finger release. A tuberculin skin test that had been performed 2.5 years earlier was negative. Medications included budesonide, azathioprine, omeprazole, metoclopramide, and losartan. Naproxen caused a rash; she had no other known allergies or history of atopy. She was from the Caribbean, lived in a city in New England, and worked in a health-related field. She drank alcohol sparingly and did not smoke or use illicit drugs. Her mother had diabetes mellitus and hypertension, and her father had had colon cancer when he was 70 years of age. A daughter had systemic lupus erythematosus; her other three children and five siblings were healthy.

Figure 2.

Clinical Photographs.
On examination, the temperature was 35.1°C, the blood pressure 178/96 mm Hg, the pulse 114 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air. The height was 165 cm, the weight 87.5 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 32.1. The upper eyelids were prominent, and the lacrimal glands were swollen bilaterally (Figure 2A). The temporal arteries were swollen, indurated, and nodular bilaterally, with strong pulses and no tenderness (Figure 2B). The sublingual glands were hypertrophic bilaterally. A nontender lymph node, measuring 1 cm in greatest dimension, was present in the posterior cervical chain. Abdominal examination revealed mild tenderness in the left lower quadrant and a palpable spleen tip. Warm synovial effusions were present in the right knee and left ankle. The left ankle was tender, and there were areas of palpable and nonpalpable purpura on both legs (Figure 2C). The remainder of the examination was normal. Blood levels of electrolytes, calcium, glucose, and alkaline phosphatase and results of renal-function tests were normal. Tests for hepatitis C virus (HCV) antibodies and hepatitis B virus core antibodies were negative. Other test results are shown in Table 1. Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 57-year-old woman was seen in the outpatient rheumatology clinic of this hospital because of fatigue, night sweats, weight loss, headache, diffuse abdominal pain, and skin lesions.

Table 1.

Laboratory Data.
The patient had been well until approximately 24 months before this evaluation, when a dry, nonproductive cough developed. Results of laboratory testing, which was performed at another hospital, are shown in Table 1.

Twenty-one months before this evaluation, when the patient was seen by her physician at another clinic, she reported persistent cough, decreased appetite, and moderate but poorly localized abdominal pain. On examination, her weight was 108.9 kg (decreased from her baseline weight of 122.5 kg 5 months earlier). A proton-pump inhibitor was administered. During the following month, fatigue and myalgias occurred, followed by the appearance of painless “red dots” around her ankles. Evaluation of a skin-biopsy specimen reportedly revealed findings consistent with early pigmented purpuric dermatosis. Blood tests revealed peripheral eosinophilia.

Twenty months before this evaluation, the patient was seen at the other hospital because of persistent cough; laboratory test results are shown in Table 1. A chest radiograph was reportedly normal. Computed tomography (CT) of the chest, abdomen, and pelvis, performed without the administration of contrast material, revealed mild, diffuse bronchial-wall thickening, a finding suggestive of chronic inflammation. Mildly enlarged lymph nodes were present in the paracardiac region, porta hepatis, mesentery, and retroperitoneum.

During the following year, multiple evaluations by consultants in allergy, rheumatology, hematology–oncology, endocrinology, and gastroenterology were performed. Nineteen months before this evaluation, esophagogastroduodenoscopy was performed, and pathological examination of biopsy specimens from the gastric antrum revealed mild chronic and focally active gastritis. Immunohistochemical staining for Helicobacter pylori was negative, and the small-bowel villi were normal.

Dr. Amita Sharma: Magnetic resonance imaging of the abdomen, performed at the other hospital 18 months before this evaluation, revealed enlarged periportal lymph nodes. No focal lesions were seen in the liver, pancreas, kidneys, spleen, or adrenal glands. There was mild splenomegaly. The pancreas was not enlarged. Sixteen months before this evaluation, CT of the chest, abdomen, and pelvis, performed after the intravenous administration of contrast material, reportedly revealed mild bronchial-wall thickening, lymphadenopathy in the axillae (with the largest node, in the right axilla, measuring 2.3 cm by 1.3 cm), an enlarged right epicardial lymph node (measuring 1.5 cm by 1.1 cm), and enlarged nodes in the portacaval, peripancreatic, and mesenteric regions (with the largest node, in the porta hepatis, measuring 4.2 cm by 2.9 cm).

Dr. Heaton: One month later, pathological examination of a right axillary lymph node revealed preserved architecture. Follicular and paracortical hyperplasia was present, along with a polytypic plasmacytosis. Immunostaining for human herpesvirus 8 (HHV-8) DNA was negative. The findings were consistent with reactive lymphadenopathy; no evidence of hematologic cancer was identified. Therapeutic trials of oral metoclopramide, cetirizine, omeprazole, and budesonide; fluticasone nasal spray; and inhaled fluticasone–salmeterol resulted in no improvement. The patient continued to lose weight.

Dr. Sharma: Thirteen months before this evaluation, 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET), performed at the other hospital, revealed FDG-avid lymph nodes in the axillae, the paracardial region, and the region of the right internal thoracic artery. The liver and spleen were enlarged and showed diffuse FDG uptake.

Dr. Heaton: Examination of a bone marrow–biopsy specimen and bone marrow aspirate revealed hypercellular bone marrow with maturing trilineage hematopoiesis, increased eosinophils, megakaryocytes, and polyclonal plasma cells, findings that are consistent with a reactive process. Biopsy of the liver was performed to investigate the hepatosplenomegaly and the FDG uptake in the liver and spleen. Pathological examination of a core needle–biopsy specimen of the liver revealed moderate-to-severe portal, periportal, and lobular inflammation that was predominantly composed of plasma cells (with polytypic expression of kappa and lambda light chains on immunohistochemical staining), with occasional eosinophils. Bile-duct proliferation, focal damage, intraepithelial lymphocytes, and scattered apoptotic hepatocytes were seen, and trichrome staining highlighted the presence of sinusoidal fibrosis. A stain for iron deposition was negative. The findings were thought to be consistent with an overlap syndrome of autoimmune hepatitis and focal sclerosing cholangitis. Treatment with prednisone was begun but was discontinued by the patient for unspecified reasons. Azathioprine therapy was also begun at this time. A decrease in abdominal pain and fatigue was reported.

Figure 1.

18F-Fluorodeoxyglucose (FDG) Positron-Emission Tomographic (PET) Scan.
Dr. Sharma: Seven months before this evaluation, an FDG-PET examination with CT for attenuation correction was performed at the other hospital (Figure 1). Splenomegaly was present, and stably enlarged FDG-avid lymph nodes were seen in the axillae, the region of the internal thoracic artery, the right paracardiac region, and the retroperitoneal, iliac, and inguinal regions. There was no hilar lymphadenopathy. There was diffuse, mild, smooth bronchial-wall thickening. No pulmonary nodules or air-space opacities were present.

Dr. Heaton: One month later, an inguinal lymph node was excised. Pathological examination revealed follicular hyperplasia and a polytypic plasmacytosis of the medulla and sinusoidal regions. On immunohistochemical studies for IgG and IgG4, a small fraction of the plasma cells were immunoreactive for IgG4. Four months before this evaluation, the patient was evaluated for a nonproductive cough, severe fatigue, weight loss, anorexia, abdominal pain, nausea, vomiting, joint pain, diffuse aches, swelling of the right knee, and night sweats. Further weight loss (to 88.5 kg from her baseline weight of 122.5 kg) was noted. Additional laboratory test results are shown in Table 1. Two months before this evaluation, severe and increasing bitemporal headache developed. The patient was referred to the rheumatology clinic of this hospital.

On evaluation at this hospital, the patient reported daily headaches and pain in her jaw when she chewed food. She did not report dry eyes or dry mouth. She had hypertension, anemia, and chronic left-knee pain after an injury that had occurred 6 years previously; she had undergone a hysterectomy and trigger-finger release. A tuberculin skin test that had been performed 2.5 years earlier was negative. Medications included budesonide, azathioprine, omeprazole, metoclopramide, and losartan. Naproxen caused a rash; she had no other known allergies or history of atopy. She was from the Caribbean, lived in a city in New England, and worked in a health-related field. She drank alcohol sparingly and did not smoke or use illicit drugs. Her mother had diabetes mellitus and hypertension, and her father had had colon cancer when he was 70 years of age. A daughter had systemic lupus erythematosus; her other three children and five siblings were healthy.

Figure 2.

Clinical Photographs.
On examination, the temperature was 35.1°C, the blood pressure 178/96 mm Hg, the pulse 114 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air. The height was 165 cm, the weight 87.5 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 32.1. The upper eyelids were prominent, and the lacrimal glands were swollen bilaterally (Figure 2A). The temporal arteries were swollen, indurated, and nodular bilaterally, with strong pulses and no tenderness (Figure 2B). The sublingual glands were hypertrophic bilaterally. A nontender lymph node, measuring 1 cm in greatest dimension, was present in the posterior cervical chain. Abdominal examination revealed mild tenderness in the left lower quadrant and a palpable spleen tip. Warm synovial effusions were present in the right knee and left ankle. The left ankle was tender, and there were areas of palpable and nonpalpable purpura on both legs (Figure 2C). The remainder of the examination was normal. Blood levels of electrolytes, calcium, glucose, and alkaline phosphatase and results of renal-function tests were normal. Tests for hepatitis C virus (HCV) antibodies and hepatitis B virus core antibodies were negative. Other test results are shown in Table 1. Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""This is a 57-year-old woman with a history of fatigue, night sweats, weight loss, headache, diffuse abdominal pain, and skin lesions. She also has a history of dry, nonproductive cough, decreased appetite, and moderate but poorly localized abdominal pain. The patient has a history of multiple evaluations by consultants in allergy, rheumatology, hematology-oncology, endocrinology, and gastroenterology. The patient's symptoms and the results of her laboratory tests suggest a systemic disease. The differential diagnosis includes lymphoma, autoimmune disease, and infectious disease. The patient's lymph node biopsy revealed preserved architecture, follicular and paracortical hyperplasia, and a polytypic plasmacytosis, which is consistent with reactive lymphadenopathy and not suggestive of lymphoma. The patient's symptoms and the results of her laboratory tests do not suggest an infectious disease. The patient's symptoms, the results of her laboratory tests, and the findings on her lymph node biopsy are most consistent with an autoimmune disease. The patient's symptoms and the results of her laboratory tests are consistent with IgG4-related disease, a systemic fibroinflammatory condition characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and often, but not always, elevated serum IgG4 concentration. The patient's symptoms, the results of her laboratory tests, and the findings on her lymph node biopsy are also consistent with systemic lupus erythematosus, a chronic autoimmune disease that can affect any part of the body. However, the patient's symptoms and the results of her laboratory tests are most consistent with IgG4-related disease.\n\nDiagnosis: IgG4-related disease.""
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10.1056/NEJMcpc1610100,Case 5-2017 — A 19-Year-Old Man with Hematuria and a Retroperitoneal Mass,,"Castleman’s disease, hyaline-vascular type.","Soft-tissue sarcoma, possibly leiomyosarcoma or malignant fibrous histiocytoma.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                   A 19-year-old man was seen in the urology outpatient clinic of this hospital because of a retroperitoneal mass and a history of transient hematuria.

The patient had been in excellent health until approximately 1 month before this evaluation, when, after hiking, he noted a small degree of hematuria, without pain, for 2 days.

Figure 1.

Transabdominal Doppler Ultrasound Image.
Figure 2.

CT Scans of the Chest and Abdomen.
Figure 3.

CT Scan and 18F-Fluorodeoxyglucose (FDG) Positron-Emission Tomographic (PET) Scan.
Dr. Kevin C. Cronin: On evaluation at a hospital near the patient’s home in South America, transabdominal and scrotal Doppler ultrasonography (Figure 1) revealed a heterogeneous, well-circumscribed mass anterior to the right common iliac artery that had prominent internal vascularity. The testes and scrotum were normal. Computed tomography (CT) of the chest, abdomen, and pelvis, performed with and without the administration of intravenous contrast material (Figure 2), revealed a well-circumscribed, solid retroperitoneal mass (2.8 cm by 3.3 cm by 4.6 cm) at the level of the pelvic inlet on the right side, anterior and medial to the psoas muscle and anterior to the right common iliac artery. The mass was solitary and had homogeneous contrast enhancement. There was a 4-mm nodule at the base of the right lung that was indeterminate. Subsequent CT and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) (Figure 3A and 3B) confirmed the presence of the well-circumscribed mass near the right psoas muscle. FDG avidity was within physiologic limits, and there was no evidence of pathologic uptake. No evidence of other pathologic conditions, upper-tract filling defects, or bladder lesions was present. There was no abnormal FDG uptake in the nodule of the right lung.

Dr. Cheng: The patient was referred to the urology outpatient clinic of this hospital. He had had excessive bleeding after a tonsillectomy and an adenoidectomy in his youth but had no subsequent bleeding during dental procedures or while he was brushing his teeth; he was otherwise in excellent health. He was physically active, with activities including running and playing soccer. He took no medications and had no known allergies. He lived in an urban area in South America and was a student. His mother had multiple sclerosis, a brother had insulin-dependent diabetes mellitus, his paternal grandfather had died of heart disease, and his father and other siblings and grandparents were healthy. He did not smoke tobacco, drink alcohol, or use illicit drugs, and he was not sexually active.

On examination, the abdomen was soft and the mass was barely palpable; there was no regional lymphadenopathy, pain, or discomfort. The remainder of the examination, including a genital examination, was normal. The white-cell count was 3300 per cubic millimeter (reference range, 4500 to 11,000), and the remainder of the complete blood count, a urinalysis, and results of coagulation and renal-function tests were normal, as were the blood levels of electrolytes, calcium, glucose, the beta subunit of human chorionic gonadotropin (_-hCG), and alpha-fetoprotein.

Dr. Cronin: Ultrasonography of the scrotum, performed at the time of the evaluation in the urology outpatient clinic of this hospital, revealed normal testes and epididymides and no change in the size of the solid retroperitoneal mass. A procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:              A 19-year-old man was seen in the urology outpatient clinic of this hospital because of a retroperitoneal mass and a history of transient hematuria.

The patient had been in excellent health until approximately 1 month before this evaluation, when, after hiking, he noted a small degree of hematuria, without pain, for 2 days.

Figure 1.

Transabdominal Doppler Ultrasound Image.
Figure 2.

CT Scans of the Chest and Abdomen.
Figure 3.

CT Scan and 18F-Fluorodeoxyglucose (FDG) Positron-Emission Tomographic (PET) Scan.
Dr. Kevin C. Cronin: On evaluation at a hospital near the patient’s home in South America, transabdominal and scrotal Doppler ultrasonography (Figure 1) revealed a heterogeneous, well-circumscribed mass anterior to the right common iliac artery that had prominent internal vascularity. The testes and scrotum were normal. Computed tomography (CT) of the chest, abdomen, and pelvis, performed with and without the administration of intravenous contrast material (Figure 2), revealed a well-circumscribed, solid retroperitoneal mass (2.8 cm by 3.3 cm by 4.6 cm) at the level of the pelvic inlet on the right side, anterior and medial to the psoas muscle and anterior to the right common iliac artery. The mass was solitary and had homogeneous contrast enhancement. There was a 4-mm nodule at the base of the right lung that was indeterminate. Subsequent CT and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) (Figure 3A and 3B) confirmed the presence of the well-circumscribed mass near the right psoas muscle. FDG avidity was within physiologic limits, and there was no evidence of pathologic uptake. No evidence of other pathologic conditions, upper-tract filling defects, or bladder lesions was present. There was no abnormal FDG uptake in the nodule of the right lung.

Dr. Cheng: The patient was referred to the urology outpatient clinic of this hospital. He had had excessive bleeding after a tonsillectomy and an adenoidectomy in his youth but had no subsequent bleeding during dental procedures or while he was brushing his teeth; he was otherwise in excellent health. He was physically active, with activities including running and playing soccer. He took no medications and had no known allergies. He lived in an urban area in South America and was a student. His mother had multiple sclerosis, a brother had insulin-dependent diabetes mellitus, his paternal grandfather had died of heart disease, and his father and other siblings and grandparents were healthy. He did not smoke tobacco, drink alcohol, or use illicit drugs, and he was not sexually active.

On examination, the abdomen was soft and the mass was barely palpable; there was no regional lymphadenopathy, pain, or discomfort. The remainder of the examination, including a genital examination, was normal. The white-cell count was 3300 per cubic millimeter (reference range, 4500 to 11,000), and the remainder of the complete blood count, a urinalysis, and results of coagulation and renal-function tests were normal, as were the blood levels of electrolytes, calcium, glucose, the beta subunit of human chorionic gonadotropin (_-hCG), and alpha-fetoprotein.

Dr. Cronin: Ultrasonography of the scrotum, performed at the time of the evaluation in the urology outpatient clinic of this hospital, revealed normal testes and epididymides and no change in the size of the solid retroperitoneal mass. A procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Paraganglioma. The patient's presentation of a retroperitoneal mass with transient hematuria, along with the imaging findings of a well-circumscribed, solid mass with homogeneous contrast enhancement, are suggestive of a paraganglioma. The lack of abnormal FDG uptake in the mass on PET scan further supports this diagnosis, as paragangliomas often show physiologic FDG uptake. The normal levels of beta-hCG and alpha-fetoprotein rule out germ cell tumors, which are another common cause of retroperitoneal masses in young men.""
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        ""content"": ""The patient is a young, healthy male who presented with a retroperitoneal mass and a history of transient hematuria. The mass was well-circumscribed, solid, and solitary with homogeneous contrast enhancement. There was no evidence of other pathologic conditions, upper-tract filling defects, or bladder lesions. The patient's blood tests were normal, including the beta subunit of human chorionic gonadotropin (_-hCG), and alpha-fetoprotein, which are tumor markers for testicular cancer. The patient's scrotum and testes were normal on examination and ultrasound. These findings suggest that the mass is not a metastasis from a testicular cancer. The location and characteristics of the mass, along with the patient's age and gender, suggest a diagnosis of a retroperitoneal tumor, possibly a primary retroperitoneal tumor such as a retroperitoneal sarcoma. \n\nDiagnosis: Retroperitoneal Sarcoma.""
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        ""content"": ""The patient is a 19-year-old male presenting with a retroperitoneal mass and a history of transient hematuria. The differential diagnosis for this patient includes renal cell carcinoma, lymphoma, retroperitoneal sarcoma, and testicular cancer with retroperitoneal metastasis. Renal cell carcinoma is less likely given the patient's age and lack of risk factors such as smoking, obesity, and hypertension. Lymphoma is a possibility given the location of the mass, but the patient lacks other common symptoms such as fever, weight loss, and night sweats. Retroperitoneal sarcoma is a possibility, but these are rare tumors and the patient lacks common symptoms such as abdominal pain and a palpable mass. Testicular cancer with retroperitoneal metastasis is less likely given the normal scrotal ultrasound. Given the patient's age, the location of the mass, and the lack of other symptoms, a retroperitoneal sarcoma is the most likely diagnosis.\n\nDiagnosis: Retroperitoneal Sarcoma""
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10.1056/NEJMcpc1613465,Case 4-2017 — A 2-Month-Old Girl with Growth Retardation and Respiratory Failure,,Pulmonary-capillary hemangiomatosis and X-linked periventricular heterotopia associated with a mutation in FLNA.,X-linked periventricular heterotopia caused by an FLNA mutation.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                     A 2-month-old girl was admitted to the pediatric intensive care unit (ICU) of this hospital because of respiratory failure, growth retardation, and failure to thrive.

The patient was born by vaginal delivery to a primigravida mother at another hospital after 39 weeks of gestation; labor was induced because of intrauterine growth retardation. The birth weight was 2.3 kg (first percentile), and Apgar scores were 6 and 8 at 1 and 5 minutes, respectively. The umbilical cord was two-vessel. The patient was admitted to the neonatal ICU. Perinatal examination reportedly revealed natal teeth, retrognathia, and global hypotonia. Laboratory testing showed hypoglycemia and thrombocytopenia, which resolved. Jaundice was present; a Coombs’ test was negative, and the patient was treated with phototherapy. No weight gain was noted during her hospitalization. She was discharged from the ICU on the 10th hospital day.

At 30 days of life, the patient was seen in the outpatient genetics clinic of the other hospital. On examination, she was reportedly in respiratory distress, with an oxygen saturation between 70 and 79% while she was breathing ambient air, and she was transferred to the ICU.

Figure 1.

Imaging Studies.
Dr. Sjirk J. Westra: A chest radiograph (Figure 1A) and computed tomography (CT) of the chest and abdomen, performed without the administration of contrast material, revealed borderline cardiomegaly, nonspecific diffuse pulmonary abnormalities, and architectural distortion of the lung parenchyma that was reminiscent of chronic lung disease of prematurity. However, since the baby was not born prematurely and was not receiving ventilatory support as a neonate but was small for gestational age, the term Wilson–Mikity syndrome (pulmonary dysmaturity syndrome)1 may be applied to describe the radiographic findings. An esophagram was normal, revealing no evidence suggestive of a vascular ring or vascular sling.

Dr. Lambert: A diagnosis of hypercarbic respiratory failure of an unknown cause was made. The patient was transferred to a second hospital.

Figure 2.

Cranial MRI.
Dr. Westra: Twenty-seven days before this admission, magnetic resonance imaging (MRI) of the head (Figure 2), performed at the second hospital, revealed extensive periventricular gray-matter heterotopia, a large cisterna magna, and micrognathia, with no evidence of intracranial venous thrombosis.

Dr. Manuella Lahoud-Rahme: Transthoracic echocardiography revealed a patent foramen ovale, a large perimembranous ventricular septal defect walled off by an aneurysmal membranous septum, and an effective small left-to-right shunt without left ventricular dilatation. There was also a competent bicuspid aortic valve with fusion of the intercoronary commissure, with trivial stenosis, aortic dilatation, and a large patent ductus arteriosus with bidirectional flow and pulmonary arterial pressures estimated to be at systemic levels, as well as preserved biventricular function.

Dr. Lambert: Genetics consultation was obtained, and results of microarray testing (GeneDx) were reportedly normal. The patient was discharged on the sixth hospital day, but she returned within 12 hours, after an episode of severe respiratory distress. A brief episode of bradycardia was observed in the pediatric department, and she was transferred to the pediatric ICU. Twenty days before admission to this hospital, an orogastric feeding tube was placed because of weight loss.

Dr. Westra: Three days later, CT angiography of the chest (Figure 1B through 1E) revealed dilatation of the ascending aorta, a large patent ductus arteriosus with a relatively small-caliber transverse aortic arch and no focal coarctation, an enlarged pulmonary-artery trunk (1.6 cm in diameter), enlarged left and right main pulmonary arteries (indicative of pulmonary hypertension), and large lung volumes. Scattered bandlike and ground-glass opacities and areas of hyperaeration were seen in both lungs.

Dr. Lahoud-Rahme: Nine days before this admission, when the patient was 7 weeks 3 days of age, cardiac catheterization was performed, and the patent ductus arteriosus was closed with the use of a 6-mm Amplatzer Vascular Plug II device. The pulmonary arterial pressure was 51/23 mm Hg (mean, 35), and the aortic pressure 53/24 mm Hg (mean, 36). There was no substantial change in the pulmonary arterial pressure after the ductus was closed (pulmonary arterial pressure, 58/19 mm Hg [mean, 36]; aortic pressure, 89/56 mm Hg [mean, 67]) or when the patient received supplemental oxygen with a fraction of inspired oxygen (Fio2) of 1.0 (pulmonary arterial pressure, 58/19 mm Hg [mean, 36]; aortic pressure, 89/56 mm Hg [mean, 67]).

Dr. Lambert: The patient was transferred back to the first hospital, which was closer to her home.

Despite closure of the patent ductus arteriosus, the patient’s respiratory status did not improve, and she required continuous positive airway pressure (CPAP) with a positive end-expiratory pressure of 6 cm of water. The patient’s interest in oral feedings decreased and continuous nasogastric tube feedings were begun, but no appreciable weight gain was noted. There was no evidence of inability to feed or of abnormalities on an esophagram. She was transferred to the pediatric ICU of this hospital. Medications on transfer were famotidine, furosemide, metoclopramide, and (as needed) simethicone for gastric distress and a glycerine suppository for constipation; she also received continuous nasogastric feeding with formula.

The patient lived with her parents and maternal relatives. Her mother had smoked during pregnancy, had taken lamotrigine for a seizure disorder that had been diagnosed when she was a teenager, and had hyperflexible joints. She and the patient’s maternal grandmother had periventricular heterotopia. A maternal half-aunt also had a seizure disorder. The patient’s father had a history of depression; two paternal half-sisters were healthy. The patient’s mother was of European ancestry; her father was of French and Polish ancestry.

On examination, the patient’s weight was 3.18 kg (below the first percentile for age), the length 48.25 cm, and the head circumference 37 cm. The maximal temperature was 37.2°C; the systemic systolic blood pressure ranged from 79 to 96 mm Hg, the diastolic blood pressure from 46 to 57 mm Hg (mean arterial pressure, 50 to 60 mm Hg), the heart rate from 120 to 140 beats per minute, and the respiratory rate from 20 to 50 breaths per minute. The sutures were open, and the facial appearance was not dysmorphic. The hair of the scalp and eyebrows was thin, and a natal tooth was present. The eyes were widely spaced, with grey–blue sclera. There were bilateral fine crackles in the lungs (with more crackles in the right lung than in the left), with mild subcostal and suprasternal retractions; no associated stridor, wheezing, grunting, or nasal flaring was present. No cardiac murmur was heard. The abdomen was soft, with bowel sounds. Muscle tone was poor, and there was poor visual tracking of a toy. When the patient was asleep, the oxygen saturation decreased to between 80 and 89% while she was receiving CPAP with a positive end-expiratory pressure of 6 cm of water through nasal prongs. As she continued to receive CPAP, the Fio2 increased to 0.4 and the oxygen saturation rose to greater than 95%.

The next day, an electrocardiogram (ECG) showed a normal sinus rhythm at a rate of 153 beats per minute and was normal for the patient’s age.

Dr. Lahoud-Rahme: On the patient’s arrival at this hospital, we performed repeat transthoracic echocardiography, which showed the findings reported earlier: the presence of a well-situated ductal occluder device, no coarctation, no residual ductal-level shunting, and normal biventricular size and function. The effective shunting across the ventricular septal defect was small (peak interventricular gradient, 40 mm Hg), with estimated right ventricular pressures at 50% of systemic levels. Interventricular septal flattening was present, which was suggestive of at least mildly elevated pulmonary arterial pressures.

Table 1.

Laboratory Data.
Dr. Lambert: Blood levels of glucose, urea nitrogen, phosphorus, magnesium, calcium, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were normal; other laboratory test results are shown in Table 1.

Dr. Lahoud-Rahme: Cardiac catheterization was performed 15 days after admission. Baseline data were obtained when the patient was receiving supplemental oxygen with an Fio2 of 0.4. The oxygen saturation was 69% in the superior vena cava and 79% in the left pulmonary artery; these findings are indicative of insubstantial left-to-right shunting (hemoglobin level, 11 g per deciliter; assumed oxygen consumption, 170 ml per minute per square meter of body-surface area; ratio of pulmonary to systemic blood flow, 1.25:1). The mean right atrial pressure was 3 mm Hg, the right ventricular pressure 44/4 mm Hg, the pulmonary arterial pressure 36/12 mm Hg (mean, 22), the aortic pressure 63/41 mm Hg (mean, 51), the pulmonary capillary wedge pressure 5 mm Hg, and the left ventricular pressure 70/6 mm Hg. Using these data, we estimated a normal systemic vascular resistance at 16 Wood units per square meter (normal range, 9 to 20) and a pulmonary vascular resistance at 3 Wood units per square meter (normal range, 0.25 to 3). Wood units, which are used by pediatric cardiologists to measure vascular resistance, are calculated by dividing the relevant pressure (in mm Hg) by cardiac output (in liters per minute). The cardiac index was 4.4 liters per minute per square meter.

After the patient received supplemental oxygen with an Fio2 of 1.0 for 10 minutes, the pulmonary arterial pressure was 28/10 mm Hg (mean, 17) and the aortic pressure was 55/36 mm Hg (mean, 44); the pulmonary vascular resistance was calculated at 2 Wood units per square meter. After the patient received inhaled nitric oxide at a concentration of 80 parts per million with an Fio2 of 1.0 for 10 minutes, the pulmonary arterial pressure was 27/9 mm Hg (mean, 15), the aortic pressure 58/41 mm Hg (mean, 48), and the pulmonary vascular resistance 2 Wood units per square meter. The pressure measurements did not indicate pulmonary arterial hypertension. Selective angiograms of the pulmonary arterial branch (Videos 1, 2, and 3, available with the full text of this article at NEJM.org) showed abnormal tortuous distal pulmonary arterial vasculature with no evidence of emboli or obstruction. The pulmonary venous return was unobstructed.

Diagnostic procedures were performed, and additional test results were received from the other hospitals.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                       A 2-month-old girl was admitted to the pediatric intensive care unit (ICU) of this hospital because of respiratory failure, growth retardation, and failure to thrive.

The patient was born by vaginal delivery to a primigravida mother at another hospital after 39 weeks of gestation; labor was induced because of intrauterine growth retardation. The birth weight was 2.3 kg (first percentile), and Apgar scores were 6 and 8 at 1 and 5 minutes, respectively. The umbilical cord was two-vessel. The patient was admitted to the neonatal ICU. Perinatal examination reportedly revealed natal teeth, retrognathia, and global hypotonia. Laboratory testing showed hypoglycemia and thrombocytopenia, which resolved. Jaundice was present; a Coombs’ test was negative, and the patient was treated with phototherapy. No weight gain was noted during her hospitalization. She was discharged from the ICU on the 10th hospital day.

At 30 days of life, the patient was seen in the outpatient genetics clinic of the other hospital. On examination, she was reportedly in respiratory distress, with an oxygen saturation between 70 and 79% while she was breathing ambient air, and she was transferred to the ICU.

Figure 1.

Imaging Studies.
Dr. Sjirk J. Westra: A chest radiograph (Figure 1A) and computed tomography (CT) of the chest and abdomen, performed without the administration of contrast material, revealed borderline cardiomegaly, nonspecific diffuse pulmonary abnormalities, and architectural distortion of the lung parenchyma that was reminiscent of chronic lung disease of prematurity. However, since the baby was not born prematurely and was not receiving ventilatory support as a neonate but was small for gestational age, the term Wilson–Mikity syndrome (pulmonary dysmaturity syndrome)1 may be applied to describe the radiographic findings. An esophagram was normal, revealing no evidence suggestive of a vascular ring or vascular sling.

Dr. Lambert: A diagnosis of hypercarbic respiratory failure of an unknown cause was made. The patient was transferred to a second hospital.

Figure 2.

Cranial MRI.
Dr. Westra: Twenty-seven days before this admission, magnetic resonance imaging (MRI) of the head (Figure 2), performed at the second hospital, revealed extensive periventricular gray-matter heterotopia, a large cisterna magna, and micrognathia, with no evidence of intracranial venous thrombosis.

Dr. Manuella Lahoud-Rahme: Transthoracic echocardiography revealed a patent foramen ovale, a large perimembranous ventricular septal defect walled off by an aneurysmal membranous septum, and an effective small left-to-right shunt without left ventricular dilatation. There was also a competent bicuspid aortic valve with fusion of the intercoronary commissure, with trivial stenosis, aortic dilatation, and a large patent ductus arteriosus with bidirectional flow and pulmonary arterial pressures estimated to be at systemic levels, as well as preserved biventricular function.

Dr. Lambert: Genetics consultation was obtained, and results of microarray testing (GeneDx) were reportedly normal. The patient was discharged on the sixth hospital day, but she returned within 12 hours, after an episode of severe respiratory distress. A brief episode of bradycardia was observed in the pediatric department, and she was transferred to the pediatric ICU. Twenty days before admission to this hospital, an orogastric feeding tube was placed because of weight loss.

Dr. Westra: Three days later, CT angiography of the chest (Figure 1B through 1E) revealed dilatation of the ascending aorta, a large patent ductus arteriosus with a relatively small-caliber transverse aortic arch and no focal coarctation, an enlarged pulmonary-artery trunk (1.6 cm in diameter), enlarged left and right main pulmonary arteries (indicative of pulmonary hypertension), and large lung volumes. Scattered bandlike and ground-glass opacities and areas of hyperaeration were seen in both lungs.

Dr. Lahoud-Rahme: Nine days before this admission, when the patient was 7 weeks 3 days of age, cardiac catheterization was performed, and the patent ductus arteriosus was closed with the use of a 6-mm Amplatzer Vascular Plug II device. The pulmonary arterial pressure was 51/23 mm Hg (mean, 35), and the aortic pressure 53/24 mm Hg (mean, 36). There was no substantial change in the pulmonary arterial pressure after the ductus was closed (pulmonary arterial pressure, 58/19 mm Hg [mean, 36]; aortic pressure, 89/56 mm Hg [mean, 67]) or when the patient received supplemental oxygen with a fraction of inspired oxygen (Fio2) of 1.0 (pulmonary arterial pressure, 58/19 mm Hg [mean, 36]; aortic pressure, 89/56 mm Hg [mean, 67]).

Dr. Lambert: The patient was transferred back to the first hospital, which was closer to her home.

Despite closure of the patent ductus arteriosus, the patient’s respiratory status did not improve, and she required continuous positive airway pressure (CPAP) with a positive end-expiratory pressure of 6 cm of water. The patient’s interest in oral feedings decreased and continuous nasogastric tube feedings were begun, but no appreciable weight gain was noted. There was no evidence of inability to feed or of abnormalities on an esophagram. She was transferred to the pediatric ICU of this hospital. Medications on transfer were famotidine, furosemide, metoclopramide, and (as needed) simethicone for gastric distress and a glycerine suppository for constipation; she also received continuous nasogastric feeding with formula.

The patient lived with her parents and maternal relatives. Her mother had smoked during pregnancy, had taken lamotrigine for a seizure disorder that had been diagnosed when she was a teenager, and had hyperflexible joints. She and the patient’s maternal grandmother had periventricular heterotopia. A maternal half-aunt also had a seizure disorder. The patient’s father had a history of depression; two paternal half-sisters were healthy. The patient’s mother was of European ancestry; her father was of French and Polish ancestry.

On examination, the patient’s weight was 3.18 kg (below the first percentile for age), the length 48.25 cm, and the head circumference 37 cm. The maximal temperature was 37.2°C; the systemic systolic blood pressure ranged from 79 to 96 mm Hg, the diastolic blood pressure from 46 to 57 mm Hg (mean arterial pressure, 50 to 60 mm Hg), the heart rate from 120 to 140 beats per minute, and the respiratory rate from 20 to 50 breaths per minute. The sutures were open, and the facial appearance was not dysmorphic. The hair of the scalp and eyebrows was thin, and a natal tooth was present. The eyes were widely spaced, with grey–blue sclera. There were bilateral fine crackles in the lungs (with more crackles in the right lung than in the left), with mild subcostal and suprasternal retractions; no associated stridor, wheezing, grunting, or nasal flaring was present. No cardiac murmur was heard. The abdomen was soft, with bowel sounds. Muscle tone was poor, and there was poor visual tracking of a toy. When the patient was asleep, the oxygen saturation decreased to between 80 and 89% while she was receiving CPAP with a positive end-expiratory pressure of 6 cm of water through nasal prongs. As she continued to receive CPAP, the Fio2 increased to 0.4 and the oxygen saturation rose to greater than 95%.

The next day, an electrocardiogram (ECG) showed a normal sinus rhythm at a rate of 153 beats per minute and was normal for the patient’s age.

Dr. Lahoud-Rahme: On the patient’s arrival at this hospital, we performed repeat transthoracic echocardiography, which showed the findings reported earlier: the presence of a well-situated ductal occluder device, no coarctation, no residual ductal-level shunting, and normal biventricular size and function. The effective shunting across the ventricular septal defect was small (peak interventricular gradient, 40 mm Hg), with estimated right ventricular pressures at 50% of systemic levels. Interventricular septal flattening was present, which was suggestive of at least mildly elevated pulmonary arterial pressures.

Table 1.

Laboratory Data.
Dr. Lambert: Blood levels of glucose, urea nitrogen, phosphorus, magnesium, calcium, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were normal; other laboratory test results are shown in Table 1.

Dr. Lahoud-Rahme: Cardiac catheterization was performed 15 days after admission. Baseline data were obtained when the patient was receiving supplemental oxygen with an Fio2 of 0.4. The oxygen saturation was 69% in the superior vena cava and 79% in the left pulmonary artery; these findings are indicative of insubstantial left-to-right shunting (hemoglobin level, 11 g per deciliter; assumed oxygen consumption, 170 ml per minute per square meter of body-surface area; ratio of pulmonary to systemic blood flow, 1.25:1). The mean right atrial pressure was 3 mm Hg, the right ventricular pressure 44/4 mm Hg, the pulmonary arterial pressure 36/12 mm Hg (mean, 22), the aortic pressure 63/41 mm Hg (mean, 51), the pulmonary capillary wedge pressure 5 mm Hg, and the left ventricular pressure 70/6 mm Hg. Using these data, we estimated a normal systemic vascular resistance at 16 Wood units per square meter (normal range, 9 to 20) and a pulmonary vascular resistance at 3 Wood units per square meter (normal range, 0.25 to 3). Wood units, which are used by pediatric cardiologists to measure vascular resistance, are calculated by dividing the relevant pressure (in mm Hg) by cardiac output (in liters per minute). The cardiac index was 4.4 liters per minute per square meter.

After the patient received supplemental oxygen with an Fio2 of 1.0 for 10 minutes, the pulmonary arterial pressure was 28/10 mm Hg (mean, 17) and the aortic pressure was 55/36 mm Hg (mean, 44); the pulmonary vascular resistance was calculated at 2 Wood units per square meter. After the patient received inhaled nitric oxide at a concentration of 80 parts per million with an Fio2 of 1.0 for 10 minutes, the pulmonary arterial pressure was 27/9 mm Hg (mean, 15), the aortic pressure 58/41 mm Hg (mean, 48), and the pulmonary vascular resistance 2 Wood units per square meter. The pressure measurements did not indicate pulmonary arterial hypertension. Selective angiograms of the pulmonary arterial branch (Videos 1, 2, and 3, available with the full text of this article at NEJM.org) showed abnormal tortuous distal pulmonary arterial vasculature with no evidence of emboli or obstruction. The pulmonary venous return was unobstructed.

Diagnostic procedures were performed, and additional test results were received from the other hospitals.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""This is a 2-month-old girl who presents with respiratory failure, growth retardation, and failure to thrive. She was born small for gestational age and has had persistent issues with weight gain. She also has a history of hypoglycemia, thrombocytopenia, and jaundice. She has natal teeth, retrognathia, and global hypotonia. She has a history of respiratory distress and has required continuous positive airway pressure. She has a large perimembranous ventricular septal defect, a patent foramen ovale, and a patent ductus arteriosus. She also has periventricular gray-matter heterotopia and a large cisterna magna. The differential diagnosis for this patient includes genetic syndromes, metabolic disorders, and congenital heart disease. Given the patient's constellation of symptoms, a genetic syndrome is most likely. The patient's mother and maternal grandmother have periventricular heterotopia, suggesting a possible genetic link. The patient's symptoms are consistent with a diagnosis of Zellweger syndrome, a rare, autosomal recessive disorder characterized by the reduction or absence of functional peroxisomes in the cells of an individual. This leads to a decreased ability to metabolize certain substances, leading to a buildup of toxic substances in various tissues, which can affect multiple systems of the body. \n\nDiagnosis: Zellweger Syndrome.""
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10.1056/NEJMcpc1613467,Case 2-2017 — An 18-Year-Old Woman with Acute Liver Failure,,Fulminant hepatic failure due to Wilson’s disease.,Fulminant hepatic failure due to Wilson’s disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                An 18-year-old woman was seen in the emergency department of this hospital 11 weeks after the birth of her first child because of acute liver failure.

The patient had been well until 1 week before this presentation, when rhinorrhea, sore throat, and cough developed. On the fourth day of illness, she was seen in an urgent care clinic because of worsening cough, wheezing, and dyspnea. Bronchitis was diagnosed, and promethazine–dextromethorphan syrup and a 5-day course of oral azithromycin were prescribed. The patient returned home.

Over the next 3 days, abdominal discomfort, nausea, vomiting, diarrhea, and vaginal bleeding developed. The patient also noted progressive yellowing of her skin and eyes. When she woke up on the morning of the current presentation, she felt light-headed. When she arose from bed, syncope occurred; the patient fell and had a laceration of the chin. Her boyfriend called emergency medical services (EMS), and a team was dispatched to the patient’s home.

On assessment by EMS personnel, the patient had jaundice and diaphoresis. She appeared fatigued. The pulse was 120 beats per minute, the blood pressure 82/56 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. Nystagmus occurred on right lateral gaze. The abdomen was distended, and tenderness was present in the right lower quadrant. The capillary blood glucose level was 121 mg per deciliter (6.7 mmol per liter), and an electrocardiogram showed sinus tachycardia. Intravenous fluids and supplemental oxygen (through a nasal cannula at a rate of 2 liters per minute) were administered, and the patient was transported to the emergency department of another hospital.

Table 1.

Laboratory Data.
On arrival at the other hospital, the patient reported burning abdominal pain, which she rated at 10 on a scale of 0 to 10, with 10 indicating the most severe pain. The temperature was 37.0°C, the pulse 88 beats per minute, the blood pressure 107/42 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The abdomen was soft, with tenderness on the right side, and there was trace edema of the legs. The results of the examination were otherwise unchanged. The blood carbon dioxide level was 21 mmol per liter (reference range, 24 to 34), and the blood glucose level was 104 mg per deciliter (5.8 mmol per liter; reference range, 70 to 100 mg per deciliter [3.9 to 5.6 mmol per liter]). The anion gap and blood levels of sodium, potassium, and chloride were normal, as were the results of renal-function tests and a serum toxicology screen, which included a test for acetaminophen. Other laboratory test results are shown in Table 1.

Figure 1.

Abdominal Ultrasound Images.
Dr. Amir H. Davarpanah: A chest radiograph and a computed tomographic (CT) scan of the head (obtained without the administration of intravenous contrast material) were normal. Ultrasonography of the abdomen revealed mildly increased hepatic parenchymal echogenicity (Figure 1A). This finding, although nonspecific, could reflect hepatic steatosis or diffuse parenchymal disease. No focal liver lesions were identified. The gallbladder was distended, with apparent wall edema, a small amount of pericholecystic fluid, and layering sludge (Figure 1B). The common bile duct was normal in diameter, with no intrahepatic biliary ductal dilatation (Figure 1C). The spleen was mildly enlarged, to a greatest longitudinal diameter of 13 cm (normal, ≤12).

Dr. Boscia: Intravenous fluids, piperacillin–tazobactam, morphine, ondansetron, and N-acetylcysteine were administered, and packed red cells were transfused. Five hours after arrival at the other hospital, the patient was transferred to the emergency department of this hospital.

In the emergency department, the patient reported that the abdominal pain and light-headedness had resolved and the nausea had decreased. She recalled that during the past several days, her gums had bled easily when she brushed her teeth and her urine had been tea-colored. She had a history of mild asthma. Eleven weeks earlier, she had given birth to her first child; after an otherwise uncomplicated pregnancy, preterm labor developed and was complicated by placental abruption, and vaginal delivery occurred at 32 weeks of gestation. The patient reported that she had remained in the hospital for 1 week after delivery because of unspecified abnormal laboratory test results. Her medications were albuterol as needed, azithromycin, and promethazine–dextromethorphan syrup; she did not take herbal remedies or supplements and had no known allergies. Immunizations were reportedly current.

Six weeks before this presentation, the patient had moved to an urban area of New England where she currently lived with her daughter, boyfriend, and boyfriend’s parents. She was of Southeast Asian descent and had been born in the United States. She did not smoke tobacco, use illicit drugs, or drink alcohol. A grandmother had unspecified liver disease.

On examination, the patient appeared tired and had marked jaundice. The temperature was 37.6°C, the pulse 90 beats per minute, the blood pressure 100/58 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. Conjunctival icterus was present. The abdomen was soft, with mild epigastric tenderness; abdominal guarding, rebound tenderness, and Murphy’s sign were absent. There was a 1.5-cm laceration on the chin. The remainder of the physical examination was normal. Examination of a peripheral-blood smear revealed smudge cells, burr cells, basophilic stippling, rouleaux formation, dysplastic neutrophils, and 1+ polychromasia. The anion gap, venous blood-gas measurements, and results of renal-function tests were normal, as were blood levels of sodium, potassium, chloride, carbon dioxide, magnesium, glucose, amylase, lipase, and fibrinogen; additional laboratory test results are shown in Table 1. Testing for urinary human chorionic gonadotropin was negative. A serum toxicology screen was negative, and a urine toxicology screen was positive for opiates and negative for all other analytes. Urinalysis revealed slightly cloudy, amber-colored urine with a specific gravity of 1.019, a pH of 6.0, 2+ bilirubin, 2+ urobilinogen, and 1+ occult blood by dipstick; there were 0 to 2 white cells and 0 to 2 red cells per high-power field. An electrocardiogram showed sinus tachycardia.

Dr. Davarpanah: Doppler ultrasonography of the abdomen revealed persistent evidence of wall edema and intraluminal sludge in the gallbladder. Murphy’s sign was absent, although this finding was not reliable because of the prior administration of analgesic agents. Pulsed-wave Doppler ultrasonography revealed normal arterial flow in the main hepatic artery (Figure 1D). There was also normal hepatopetal flow in the portal veins (Figure 1E) and hepatofugal flow in the hepatic veins (Figure 1F).

Dr. Boscia: The administration of N-acetylcysteine was continued, and the chin laceration was sutured. Additional laboratory tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:            An 18-year-old woman was seen in the emergency department of this hospital 11 weeks after the birth of her first child because of acute liver failure.

The patient had been well until 1 week before this presentation, when rhinorrhea, sore throat, and cough developed. On the fourth day of illness, she was seen in an urgent care clinic because of worsening cough, wheezing, and dyspnea. Bronchitis was diagnosed, and promethazine–dextromethorphan syrup and a 5-day course of oral azithromycin were prescribed. The patient returned home.

Over the next 3 days, abdominal discomfort, nausea, vomiting, diarrhea, and vaginal bleeding developed. The patient also noted progressive yellowing of her skin and eyes. When she woke up on the morning of the current presentation, she felt light-headed. When she arose from bed, syncope occurred; the patient fell and had a laceration of the chin. Her boyfriend called emergency medical services (EMS), and a team was dispatched to the patient’s home.

On assessment by EMS personnel, the patient had jaundice and diaphoresis. She appeared fatigued. The pulse was 120 beats per minute, the blood pressure 82/56 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. Nystagmus occurred on right lateral gaze. The abdomen was distended, and tenderness was present in the right lower quadrant. The capillary blood glucose level was 121 mg per deciliter (6.7 mmol per liter), and an electrocardiogram showed sinus tachycardia. Intravenous fluids and supplemental oxygen (through a nasal cannula at a rate of 2 liters per minute) were administered, and the patient was transported to the emergency department of another hospital.

Table 1.

Laboratory Data.
On arrival at the other hospital, the patient reported burning abdominal pain, which she rated at 10 on a scale of 0 to 10, with 10 indicating the most severe pain. The temperature was 37.0°C, the pulse 88 beats per minute, the blood pressure 107/42 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The abdomen was soft, with tenderness on the right side, and there was trace edema of the legs. The results of the examination were otherwise unchanged. The blood carbon dioxide level was 21 mmol per liter (reference range, 24 to 34), and the blood glucose level was 104 mg per deciliter (5.8 mmol per liter; reference range, 70 to 100 mg per deciliter [3.9 to 5.6 mmol per liter]). The anion gap and blood levels of sodium, potassium, and chloride were normal, as were the results of renal-function tests and a serum toxicology screen, which included a test for acetaminophen. Other laboratory test results are shown in Table 1.

Figure 1.

Abdominal Ultrasound Images.
Dr. Amir H. Davarpanah: A chest radiograph and a computed tomographic (CT) scan of the head (obtained without the administration of intravenous contrast material) were normal. Ultrasonography of the abdomen revealed mildly increased hepatic parenchymal echogenicity (Figure 1A). This finding, although nonspecific, could reflect hepatic steatosis or diffuse parenchymal disease. No focal liver lesions were identified. The gallbladder was distended, with apparent wall edema, a small amount of pericholecystic fluid, and layering sludge (Figure 1B). The common bile duct was normal in diameter, with no intrahepatic biliary ductal dilatation (Figure 1C). The spleen was mildly enlarged, to a greatest longitudinal diameter of 13 cm (normal, ≤12).

Dr. Boscia: Intravenous fluids, piperacillin–tazobactam, morphine, ondansetron, and N-acetylcysteine were administered, and packed red cells were transfused. Five hours after arrival at the other hospital, the patient was transferred to the emergency department of this hospital.

In the emergency department, the patient reported that the abdominal pain and light-headedness had resolved and the nausea had decreased. She recalled that during the past several days, her gums had bled easily when she brushed her teeth and her urine had been tea-colored. She had a history of mild asthma. Eleven weeks earlier, she had given birth to her first child; after an otherwise uncomplicated pregnancy, preterm labor developed and was complicated by placental abruption, and vaginal delivery occurred at 32 weeks of gestation. The patient reported that she had remained in the hospital for 1 week after delivery because of unspecified abnormal laboratory test results. Her medications were albuterol as needed, azithromycin, and promethazine–dextromethorphan syrup; she did not take herbal remedies or supplements and had no known allergies. Immunizations were reportedly current.

Six weeks before this presentation, the patient had moved to an urban area of New England where she currently lived with her daughter, boyfriend, and boyfriend’s parents. She was of Southeast Asian descent and had been born in the United States. She did not smoke tobacco, use illicit drugs, or drink alcohol. A grandmother had unspecified liver disease.

On examination, the patient appeared tired and had marked jaundice. The temperature was 37.6°C, the pulse 90 beats per minute, the blood pressure 100/58 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. Conjunctival icterus was present. The abdomen was soft, with mild epigastric tenderness; abdominal guarding, rebound tenderness, and Murphy’s sign were absent. There was a 1.5-cm laceration on the chin. The remainder of the physical examination was normal. Examination of a peripheral-blood smear revealed smudge cells, burr cells, basophilic stippling, rouleaux formation, dysplastic neutrophils, and 1+ polychromasia. The anion gap, venous blood-gas measurements, and results of renal-function tests were normal, as were blood levels of sodium, potassium, chloride, carbon dioxide, magnesium, glucose, amylase, lipase, and fibrinogen; additional laboratory test results are shown in Table 1. Testing for urinary human chorionic gonadotropin was negative. A serum toxicology screen was negative, and a urine toxicology screen was positive for opiates and negative for all other analytes. Urinalysis revealed slightly cloudy, amber-colored urine with a specific gravity of 1.019, a pH of 6.0, 2+ bilirubin, 2+ urobilinogen, and 1+ occult blood by dipstick; there were 0 to 2 white cells and 0 to 2 red cells per high-power field. An electrocardiogram showed sinus tachycardia.

Dr. Davarpanah: Doppler ultrasonography of the abdomen revealed persistent evidence of wall edema and intraluminal sludge in the gallbladder. Murphy’s sign was absent, although this finding was not reliable because of the prior administration of analgesic agents. Pulsed-wave Doppler ultrasonography revealed normal arterial flow in the main hepatic artery (Figure 1D). There was also normal hepatopetal flow in the portal veins (Figure 1E) and hepatofugal flow in the hepatic veins (Figure 1F).

Dr. Boscia: The administration of N-acetylcysteine was continued, and the chin laceration was sutured. Additional laboratory tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Acute fatty liver of pregnancy. The patient's symptoms of jaundice, abdominal discomfort, nausea, vomiting, and diarrhea, along with her recent childbirth, suggest a liver-related issue. The ultrasound showing increased hepatic parenchymal echogenicity could indicate hepatic steatosis, which is a common feature of acute fatty liver of pregnancy. The patient's lab results also show elevated liver enzymes and bilirubin, which are consistent with liver disease. The absence of other causes of liver disease (such as viral hepatitis, drug-induced liver injury, or autoimmune hepatitis) further supports the diagnosis of acute fatty liver of pregnancy.""
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        ""content"": ""The patient is an 18-year-old woman presenting with acute liver failure, jaundice, and recent history of bronchitis. The differential diagnosis for this patient includes viral hepatitis, drug-induced liver injury, autoimmune hepatitis, and postpartum angiopathy. The patient's recent history of bronchitis and the use of azithromycin and promethazine-dextromethorphan syrup could suggest drug-induced liver injury. However, these medications are not typically associated with liver injury. The patient's recent childbirth could suggest postpartum angiopathy, but this is usually associated with neurological symptoms, which the patient does not have. The patient's young age and the acute onset of her symptoms could suggest autoimmune hepatitis, but this is less likely without other symptoms of autoimmune disease. The patient's symptoms of rhinorrhea, sore throat, and cough, followed by the development of liver failure and jaundice, are most suggestive of viral hepatitis. The patient's recent move to an urban area could have exposed her to the virus. \n\nDiagnosis: Viral Hepatitis.""
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10.1056/NEJMcpc1613459,Case 1-2017 — A 70-Year-Old Woman with Gradually Progressive Loss of Language,,"Primary progressive aphasia, semantic variant, due to TAR DNA-binding protein 43 (TDP-43)–associated frontotemporal lobar degeneration, type C.","Primary progressive aphasia, semantic variant.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  A 70-year-old woman was seen in the memory disorders clinic of this hospital because of progressive cognitive difficulties involving word finding. She was interviewed with the assistance of her daughter.

The patient had reportedly been well until approximately 8 years before this evaluation, when gradually progressive difficulties with word finding developed, along with associated confusion about the meaning of some words. For example, during a conversation about a recent family event, she did not understand what the phrase “punch bowl” meant. She also had increased egocentric behavior, during which she spoke most frequently about herself. She had a good memory for recent events of her life and could recount multiple stories (at times to an excessive extent during history taking, such that she required refocusing). She had an excellent sense of direction. She had an uncharacteristically matter-of-fact reaction to the death of a sibling and of her dog (being less upset than her family expected). She occasionally had mildly inappropriate behavior, such as saying “I love you” to people to whom she was not particularly close.

The patient was right-handed. Approximately 10 years earlier, she had a tick bite and was treated with antibiotic agents after a test for Lyme disease was positive. When she was 7 years of age, she fell out of a tree and hit her head, but she did not lose consciousness and was not hospitalized. There was no history of recent head injury, stroke, seizure, transient ischemic attack, meningitis, encephalitis, exposure to human immunodeficiency virus, thyroid disorder, heart disease, hypertension, hyperlipidemia, diabetes mellitus, liver disease, kidney disease, cancer, pulmonary disorders, exposure to heavy metals, or learning disability. Her only surgical history included three cesarean sections. Her medications were a multivitamin, vitamin C, ginkgo biloba, calcium, magnesium, and zinc, and she had no known allergies. Since the death of her husband 10 years earlier, she had lived alone (in a different state than her daughter) and was able to perform all activities of daily living independently, including managing her money, paying bills, and volunteering in the community (i.e., visiting senior centers to play piano and attending regular community choir practices). She drank alcohol once or twice per month and did not smoke or use illicit drugs. She had been a teacher and had later worked in business with her husband until his death. A brother in his 60s had Parkinson’s disease, and a sister in her 80s had Parkinson’s disease and dementia. Her six children and her grandchildren were healthy.

On examination, the patient was alert, attentive, well-groomed, cooperative, and pleasant. The blood pressure was 120/70 mm Hg, the pulse 78 beats per minute and regular, and the weight 68.6 kg. She had a score on the Mini–Mental State Examination of 28 (with scores ranging from 0 to 30 and higher scores indicating better cognitive function), because she was unable to recall the name of the hospital or the county. She had a score on the Clinical Dementia Rating scale of 0 (with scores ranging from 0 to 3 and lower scores indicating better cognitive function). The neurologic examination was normal, including evaluation of the 2nd through 12th cranial nerves, power, bulk, tone, coordination, stance, and gait; the deep tendon reflexes were 1+ throughout. The platelet count was 362,000 per cubic millimeter (reference range, 150,000 to 350,000), and the folate level was 20 ng per milliliter (45 nmol per liter; reference range, 3 to 17 ng per milliliter [7 to 39 nmol per liter]). The hematocrit, hemoglobin level, white-cell count, and blood levels of vitamin B12, electrolytes, glucose, calcium, total protein, albumin, globulin, and thyrotropin were normal, as were the results of renal- and liver-function tests. A rapid plasma reagin test was nonreactive, and testing for antibodies to Borrelia burgdorferi was negative. As part of the standard evaluation for a suspected cognitive impairment, the patient was referred for neuropsychological testing, speech pathological evaluation, and imaging studies of the head.

Dr. Janet C. Sherman: On neuropsychological testing, the patient’s performance on a screen of nonverbal abilities indicated that she had average premorbid intellectual abilities. Language impairment was evident both through clinical observations and when she performed verbal tasks, including tasks of confrontation naming, verbal fluency (for which she had substantially more difficulty with semantic fluency than with phonemic fluency), verbal abstraction, and comprehension of individual words. Her spontaneous speech was fluent, but she had notable difficulty with word finding and made occasional paraphasic errors. She often had difficulty comprehending words, such as “cork,” “misplaced,” “bored,” and “pessimism.” Her performance on tests of attention and executive functioning varied; her greatest impairments were evident when the tasks required language mediation, and these impairments contrasted with her generally normal performance on tasks that were not verbally mediated. Similarly, her performance was normal on a test of nonverbal memory but was substantially impaired on a test of verbal memory. Her storage of verbal information was difficult to assess because of her impaired acquisition and anomia. Her storage of nonverbal information was normal, as was her performance on visuospatial tasks. She did not report symptoms of depression or anxiety on self-reported assessments.

Ms. Daisy Hochberg: Speech pathological evaluation revealed that the patient had fluent, articulate speech with pauses for word finding, vague word substitutions, and circumlocutions. She was somewhat tangential in her speech and was fixated on telling stories from her life, such that she required frequent refocusing on the topic at hand. She had substantial impairment on a test of naming, with superordinate responses, and she had impairment on word–picture matching. Rare phonemic paraphasias were present. Auditory comprehension was impaired for words she no longer recognized and for sentences with complex syntax. Sentence repetition was intact. A written language assessment revealed that she could read normally and had mild agrammatism in written language samples. A semantic picture–picture matching test revealed no evidence of visual agnosia. (A portion of the speech pathological evaluation is shown in Video 1, available with the full text of this article at NEJM.org.)

Dr. Dickerson: A clinical diagnosis was made, and additional diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                A 70-year-old woman was seen in the memory disorders clinic of this hospital because of progressive cognitive difficulties involving word finding. She was interviewed with the assistance of her daughter.

The patient had reportedly been well until approximately 8 years before this evaluation, when gradually progressive difficulties with word finding developed, along with associated confusion about the meaning of some words. For example, during a conversation about a recent family event, she did not understand what the phrase “punch bowl” meant. She also had increased egocentric behavior, during which she spoke most frequently about herself. She had a good memory for recent events of her life and could recount multiple stories (at times to an excessive extent during history taking, such that she required refocusing). She had an excellent sense of direction. She had an uncharacteristically matter-of-fact reaction to the death of a sibling and of her dog (being less upset than her family expected). She occasionally had mildly inappropriate behavior, such as saying “I love you” to people to whom she was not particularly close.

The patient was right-handed. Approximately 10 years earlier, she had a tick bite and was treated with antibiotic agents after a test for Lyme disease was positive. When she was 7 years of age, she fell out of a tree and hit her head, but she did not lose consciousness and was not hospitalized. There was no history of recent head injury, stroke, seizure, transient ischemic attack, meningitis, encephalitis, exposure to human immunodeficiency virus, thyroid disorder, heart disease, hypertension, hyperlipidemia, diabetes mellitus, liver disease, kidney disease, cancer, pulmonary disorders, exposure to heavy metals, or learning disability. Her only surgical history included three cesarean sections. Her medications were a multivitamin, vitamin C, ginkgo biloba, calcium, magnesium, and zinc, and she had no known allergies. Since the death of her husband 10 years earlier, she had lived alone (in a different state than her daughter) and was able to perform all activities of daily living independently, including managing her money, paying bills, and volunteering in the community (i.e., visiting senior centers to play piano and attending regular community choir practices). She drank alcohol once or twice per month and did not smoke or use illicit drugs. She had been a teacher and had later worked in business with her husband until his death. A brother in his 60s had Parkinson’s disease, and a sister in her 80s had Parkinson’s disease and dementia. Her six children and her grandchildren were healthy.

On examination, the patient was alert, attentive, well-groomed, cooperative, and pleasant. The blood pressure was 120/70 mm Hg, the pulse 78 beats per minute and regular, and the weight 68.6 kg. She had a score on the Mini–Mental State Examination of 28 (with scores ranging from 0 to 30 and higher scores indicating better cognitive function), because she was unable to recall the name of the hospital or the county. She had a score on the Clinical Dementia Rating scale of 0 (with scores ranging from 0 to 3 and lower scores indicating better cognitive function). The neurologic examination was normal, including evaluation of the 2nd through 12th cranial nerves, power, bulk, tone, coordination, stance, and gait; the deep tendon reflexes were 1+ throughout. The platelet count was 362,000 per cubic millimeter (reference range, 150,000 to 350,000), and the folate level was 20 ng per milliliter (45 nmol per liter; reference range, 3 to 17 ng per milliliter [7 to 39 nmol per liter]). The hematocrit, hemoglobin level, white-cell count, and blood levels of vitamin B12, electrolytes, glucose, calcium, total protein, albumin, globulin, and thyrotropin were normal, as were the results of renal- and liver-function tests. A rapid plasma reagin test was nonreactive, and testing for antibodies to Borrelia burgdorferi was negative. As part of the standard evaluation for a suspected cognitive impairment, the patient was referred for neuropsychological testing, speech pathological evaluation, and imaging studies of the head.

Dr. Janet C. Sherman: On neuropsychological testing, the patient’s performance on a screen of nonverbal abilities indicated that she had average premorbid intellectual abilities. Language impairment was evident both through clinical observations and when she performed verbal tasks, including tasks of confrontation naming, verbal fluency (for which she had substantially more difficulty with semantic fluency than with phonemic fluency), verbal abstraction, and comprehension of individual words. Her spontaneous speech was fluent, but she had notable difficulty with word finding and made occasional paraphasic errors. She often had difficulty comprehending words, such as “cork,” “misplaced,” “bored,” and “pessimism.” Her performance on tests of attention and executive functioning varied; her greatest impairments were evident when the tasks required language mediation, and these impairments contrasted with her generally normal performance on tasks that were not verbally mediated. Similarly, her performance was normal on a test of nonverbal memory but was substantially impaired on a test of verbal memory. Her storage of verbal information was difficult to assess because of her impaired acquisition and anomia. Her storage of nonverbal information was normal, as was her performance on visuospatial tasks. She did not report symptoms of depression or anxiety on self-reported assessments.

Ms. Daisy Hochberg: Speech pathological evaluation revealed that the patient had fluent, articulate speech with pauses for word finding, vague word substitutions, and circumlocutions. She was somewhat tangential in her speech and was fixated on telling stories from her life, such that she required frequent refocusing on the topic at hand. She had substantial impairment on a test of naming, with superordinate responses, and she had impairment on word–picture matching. Rare phonemic paraphasias were present. Auditory comprehension was impaired for words she no longer recognized and for sentences with complex syntax. Sentence repetition was intact. A written language assessment revealed that she could read normally and had mild agrammatism in written language samples. A semantic picture–picture matching test revealed no evidence of visual agnosia. (A portion of the speech pathological evaluation is shown in Video 1, available with the full text of this article at NEJM.org.)

Dr. Dickerson: A clinical diagnosis was made, and additional diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms include progressive difficulties with word finding, confusion about the meaning of some words, increased egocentric behavior, and occasional mildly inappropriate behavior. These symptoms suggest a cognitive disorder. The patient's memory for recent events is good, and she has an excellent sense of direction, which suggests that her cognitive difficulties are not due to a global cognitive impairment such as Alzheimer's disease. The patient's language impairment is evident in her difficulty with confrontation naming, verbal fluency, verbal abstraction, and comprehension of individual words. Her spontaneous speech is fluent, but she has notable difficulty with word finding and makes occasional paraphasic errors. These symptoms suggest a language-based cognitive disorder. The patient's performance on tests of attention and executive functioning varies, with her greatest impairments evident when the tasks require language mediation. This further supports a language-based cognitive disorder. The patient's performance is normal on a test of nonverbal memory but is substantially impaired on a test of verbal memory. This suggests that her cognitive difficulties are not due to a memory disorder. The patient's performance on visuospatial tasks is normal, which suggests that her cognitive difficulties are not due to a visuospatial disorder. The patient does not report symptoms of depression or anxiety, which suggests that her cognitive difficulties are not due to a mood disorder. The patient's speech is fluent and articulate, but she has pauses for word finding, vague word substitutions, and circumlocutions. She is somewhat tangential in her speech and is fixated on telling stories from her life. These symptoms suggest a language-based cognitive disorder. The patient has substantial impairment on a test of naming and impairment on word-picture matching. These symptoms suggest a language-based cognitive disorder. The patient's auditory comprehension is impaired for words she no longer recognizes and for sentences with complex syntax. This suggests a language-based cognitive disorder. The patient's sentence repetition is intact, which suggests that her cognitive difficulties are not due to a motor speech disorder. The patient can read normally and has mild agrammatism in written language samples. This suggests a language-based cognitive disorder. The patient's performance on a semantic picture-picture matching test reveals no evidence of visual agnosia, which suggests that her cognitive difficulties are not due to a visual perceptual disorder.\n\nDiagnosis: Primary Progressive Aphasia""
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        ""content"": ""The patient is a 70-year-old woman presenting with progressive cognitive difficulties, specifically with word finding and understanding the meaning of some words. She also exhibits egocentric behavior and occasional mildly inappropriate behavior. Her memory for recent events is good and she has an excellent sense of direction. She has no history of recent head injury, stroke, seizure, transient ischemic attack, meningitis, encephalitis, exposure to human immunodeficiency virus, thyroid disorder, heart disease, hypertension, hyperlipidemia, diabetes mellitus, liver disease, kidney disease, cancer, pulmonary disorders, exposure to heavy metals, or learning disability. Her only surgical history included three cesarean sections. Her medications were a multivitamin, vitamin C, ginkgo biloba, calcium, magnesium, and zinc, and she had no known allergies. She is able to perform all activities of daily living independently. She has a family history of Parkinson's disease and dementia. \n\nThe differential diagnosis for this patient includes Alzheimer's disease, frontotemporal dementia, vascular dementia, and primary progressive aphasia. Alzheimer's disease is less likely given the patient's good memory for recent events and excellent sense of direction. Vascular dementia is also less likely given the absence of a history of stroke or transient ischemic attack. Frontotemporal dementia is a possibility given the patient's egocentric behavior and occasional mildly inappropriate behavior. However, the patient's primary symptom is difficulty with word finding and understanding the meaning of some words, which is most consistent with primary progressive aphasia. \n\nDiagnosis: Primary Progressive Aphasia.""
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10.1056/NEJMcpc1613468,Case 40-2016 — A 14-Month-Old Girl with Recurrent Vomiting,,Aqueductal stenosis with hydrocephalus.,"Increased intracranial pressure, possibly due to hydrocephalus.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 A girl 14 months 19 days of age was admitted to a community hospital affiliated with this hospital because of episodes of recurrent vomiting.

The patient had been well until she was 11 months 12 days of age, when intermittent vomiting developed. On the fourth day of symptoms, she was seen by a pediatrician. The stools were reportedly soft but formed, with no diarrhea. A diagnosis of viral gastroenteritis was made, and dietary changes were advised. The patient returned home, and the symptoms resolved. On routine examination when she was 12 months of age, her parents reported that she could perform activities that were developmentally appropriate for her age, including walking, holding on, and using a cup; physical examination was normal. Routine childhood immunizations were administered.

Table 1.

Laboratory Data Obtained at the Other Hospital.
During the next 2 months, the patient had two episodes of recurrent vomiting; the episodes lasted 3 days and 5 days and were associated with lethargy and decreased oral intake, as well as with diarrhea on some but not all occasions. During each episode, an examination performed in the emergency department of the other hospital was normal, and no fever or abdominal pain was present. Laboratory test results are shown in Table 1. A diagnosis of acute gastroenteritis with dehydration was made during each episode. Ondansetron and intravenous fluids were administered, and the patient returned home. The episodes resolved spontaneously. Three weeks before the current admission, milk formula was stopped and a soy-based formula was begun.

Eighteen days before the current admission to the other hospital, the patient was seen by a pediatric gastroenterologist at this hospital. Examination was normal, and a possible diagnosis of vomiting caused by nonketotic hypoglycemia was made. Her parents were advised to seek a medical evaluation for her, including metabolic studies, if another episode occurred.

On the day of admission, four episodes of nonbloody, nonbilious vomiting occurred in the evening, and the patient was taken to the emergency department of the other hospital. The patient had been born at full-term gestation, without complications during gestation or delivery. The weight at birth was 3.3 kg, and the length 50.2 cm. The Apgar scores at 1 minute and 5 minutes were 8 and 9, respectively. Jaundice was noted during the newborn period. The patient was breast-fed exclusively for 8 weeks and received supplemental formula thereafter, and solid foods were introduced at 5 months. She had mild facial eczema. She received no medications and had no known allergies. Her father had gallstones and had had pancreatitis in his 20s, her paternal grandmother had gallstones, her paternal grandfather had colon cancer, both grandfathers had diabetes mellitus, her maternal grandfather had arthritis, and a distant paternal cousin had Crohn’s disease; there was no family history of celiac disease.

On examination in the emergency department, the patient vomited and had dry heaves intermittently. There was a regular heart rate and rhythm, and the temperature, respiratory rate, and remainder of the general examination were normal. Blood levels of amylase, lipase, ammonia, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, pyruvate kinase, and amino acids were normal; other test results are shown in Table 1. Urinalysis revealed 1+ ketones and leukocyte esterase by dipstick and 5 white cells per high-power field; screening for toxins in the urine was negative, and a urine culture was sterile. A presumptive diagnosis of gastroenteritis was made, and the patient was admitted to the pediatric inpatient unit for observation and rehydration.

On admission to the pediatric inpatient unit, additional history was obtained from the patient’s parents. They reported that in retrospect, during the previous 3 months, the patient had stopped pulling to stand or attempting to walk and was only crawling (and when doing so appeared to be unsteady, with occasional “face plants”). They noted occasional “shakes” when she woke up in the morning, which consisted of symmetric movement for a few seconds that would recur over a 10-minute period, without loss of tone or consciousness.

Figure 1.

Growth Charts.
On examination, the patient was alert and interactive. Frontal bossing was present and the fontanelle was full, with mild pulsations that were visible anteriorly when she was in the supine position. The weight was 9.9 kg, the length 78.3 cm, and the head circumference 51.5 cm (>95th percentile). The eye movements were normal, the pupils were equally reactive, and there was no horizontal or vertical limitation or nystagmus. The legs had decreased muscle tone, with brisk 3+ patellar reflexes, and the plantar reflexes were flexor. There was no crossed adductor reflex (i.e., no contraction of both hip adductors when the knee jerk was elicited on either side, which is a sign of pyramidal tract dysfunction in patients older than 8 months of age) and no ankle clonus. The remainder of the examination was normal, including evaluation of the muscle tone in the shoulder girdle. The hematocrit, hemoglobin level, red-cell indexes, white-cell count, and white-cell differential count were normal; additional laboratory test results are shown in Table 1. The patient’s pediatrician was contacted for additional information about her growth (Figure 1).

A diagnostic test was performed, and the patient was transferred to this hospital for further evaluation and treatment.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  

Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Maple Syrup Urine Disease (MSUD)\n\nThe patient's recurrent episodes of vomiting, lethargy, and decreased oral intake, along with the presence of ketones in the urine, suggest a metabolic disorder. The fact that these episodes resolved spontaneously and were not associated with fever or abdominal pain rules out common causes of vomiting such as gastroenteritis. The patient's developmental regression and abnormal neurological findings (decreased muscle tone in the legs, brisk patellar reflexes) further support a metabolic disorder affecting the nervous system. The patient's normal blood levels of amylase, lipase, ammonia, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, pyruvate kinase, and amino acids rule out many other metabolic disorders, leaving Maple Syrup Urine Disease (MSUD) as the most likely diagnosis. MSUD is a rare inherited disorder characterized by the body's inability to break down certain amino acids, leading to a buildup of these substances in the blood and urine. This buildup can cause neurological symptoms and developmental delay.""
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        ""content"": ""The patient's symptoms include recurrent vomiting, lethargy, decreased oral intake, and occasional diarrhea. These symptoms, along with the patient's developmental regression (stopped pulling to stand or attempting to walk and was only crawling) and occasional morning \""shakes\"", suggest a possible metabolic disorder. The patient's normal laboratory results, including normal blood levels of amylase, lipase, ammonia, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, pyruvate kinase, and amino acids, rule out many common metabolic disorders. However, the presence of ketones in the urine could indicate a disorder of fatty acid oxidation. The patient's symptoms seem to worsen during periods of fasting or illness, which is typical of metabolic disorders that cause energy deficiency. The patient's large head circumference could be due to hydrocephalus, which can occur in certain metabolic disorders. \n\nDiagnosis: Metabolic disorder, possibly a disorder of fatty acid oxidation.""
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}","Metabolic disorder, possibly a disorder of fatty acid oxidation",N,"{
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        ""content"": ""A 45-year-old woman was admitted to the hospital because of a 2-week history of fever, fatigue, and a rash. The patient had been well until 2 weeks before this admission, when she developed a fever, fatigue, and a rash on her trunk and extremities. She also reported a 10-pound weight loss over the past month. She had no history of recent travel, sick contacts, or changes in her diet. She had no known drug allergies and was not taking any medications. She had a history of hypertension and was a former smoker. On physical examination, the patient appeared ill. Her temperature was 38.5\u00b0C, blood pressure was 110/70 mm Hg, pulse rate was 90 beats per minute, and respiratory rate was 16 breaths per minute. She had a diffuse, maculopapular rash on her trunk and extremities. There was no lymphadenopathy or hepatosplenomegaly. The remainder of the examination was normal. Laboratory studies showed a white blood cell count of 12,000 per cubic millimeter, with 70% neutrophils, 20% lymphocytes, and 10% monocytes. The hemoglobin level was 10 g per deciliter, and the platelet count was 150,000 per cubic millimeter. The erythrocyte sedimentation rate was 50 mm per hour. The serum creatinine level was 1.0 mg per deciliter, and the serum albumin level was 3.0 g per deciliter. The alanine aminotransferase level was 40 U per liter, and the aspartate aminotransferase level was 45 U per liter. The alkaline phosphatase level was 100 U per liter, and the total bilirubin level was 1.0 mg per deciliter. The serum lactate dehydrogenase level was 500 U per liter. The serum protein electrophoresis showed a polyclonal increase in gamma globulins. The antinuclear antibody titer was 1:160, and the rheumatoid factor was 80 IU per milliliter. The serum complement levels were normal. The hepatitis B and C serologies were negative. The HIV antibody test was negative. A chest radiograph showed no abnormalities. A skin biopsy of a lesion on the patient's arm showed a dense, perivascular lymphocytic infiltrate with numerous plasma cells. Immunofluorescence studies showed granular deposits of IgG and C3 along the dermoepidermal junction.\n\nRationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):\nThe patient's presentation of fever, fatigue, rash, and weight loss is suggestive of an inflammatory or autoimmune process. The differential diagnosis includes systemic lupus erythematosus (SLE), rheumatoid arthritis, vasculitis, and lymphoma. The patient's laboratory findings of an elevated erythrocyte sedimentation rate, polyclonal increase in gamma globulins, and positive antinuclear antibody titer further support an autoimmune process. The skin biopsy showing a lymphocytic infiltrate with plasma cells and granular deposits of IgG and C3 along the dermoepidermal junction is characteristic of lupus erythematosus. The absence of lymphadenopathy or hepatosplenomegaly makes lymphoma less likely. The patient does not have joint pain or swelling, which makes rheumatoid arthritis less likely. The normal complement levels and absence of symptoms such as sinusitis or hematuria make vasculitis less likely. Therefore, the most likely diagnosis is systemic lupus erythematosus.\n\nDiagnosis:\nSystemic Lupus Erythematosus.""
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}",Systemic Lupus Erythematosus,N
10.1056/NEJMcpc1613458,Case 39-2016 — A 74-Year-Old Man with Rectal Bleeding and a History of Prostate Cancer,,"Anal squamous-cell carcinoma, positive for human papillomavirus, after brachytherapy for prostate cancer.","Anal squamous-cell carcinoma, positive for human papillomavirus, after brachytherapy for prostate cancer.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 74-year-old man with a history of prostate cancer that had been treated with brachytherapy was seen in an outpatient clinic of this hospital because of rectal bleeding of 6 months’ duration.

The patient had been well until approximately 6 months before the current evaluation, when he noted small amounts of fresh red blood with defecation. The blood was not mixed with the stool. Two months before this evaluation, the caliber of his stool decreased.

On evaluation, the patient reported daily bowel movements and no abdominal pain or weight loss. He had had a normal colonoscopy 3 years earlier, and he had no history of rectal or abdominal surgery. Nine years before this evaluation, an elevated level of prostate-specific antigen had been noted on routine screening, and a biopsy of the prostate had been performed.

Figure 1.

Biopsy Specimens and Colonoscopy Findings.
Dr. Lawrence R. Zukerberg: Five core-biopsy specimens had been procured from each side of the prostate (Figure 1A). Cancer was present in four of the five specimens from the right side and one of the five specimens from the left side. Both sides contained moderately differentiated adenocarcinoma, with a Gleason grade of 3 and a Gleason score of 6. Prostate cancer is graded with the use of the Gleason grading and scoring system. Gleason grades range from 1 to 5, with higher grades indicating more aggressive disease; most prostate cancers are Gleason grade 3, as in this case. More than one grade of cancer may be present in a biopsy sample. An overall Gleason score is calculated by adding two Gleason grades, the most extensive grade detected and the highest grade detected; in this case, specimens from both sides had a Gleason score of 6 (3 plus 3).

Dr. Hong: Imaging studies obtained at that time revealed no evidence of metastases. The patient was treated with iodine-125 brachytherapy (at a total dose of 144 Gy).

The patient also had hyperlipidemia, obesity, and multiple actinic keratoses and had undergone excision of several cutaneous squamous-cell and basal-cell carcinomas. Medications were atorvastatin and aspirin (81 mg daily). He had no known allergies, and he drank alcohol occasionally and did not smoke tobacco. He was retired and lived alone and had previously worked in an office position. A sister had died in her 70s of cancer, and another sister had died at 69 years of age of non-Hodgkin’s lymphoma.

On examination, the patient appeared well. He had a systolic murmur (grade 2/6), small external hemorrhoids, and mild-to-moderate abdominal adiposity with no tenderness, masses, or organomegaly. The inguinal regions were normal on palpation, with no inguinal lymphadenopathy. The pedal pulses were normal, and there was no leg edema. Digital rectal examination revealed a firm mass in the lower right lateral rectum that started 1 cm from the anal verge and extended 4 cm proximally from the posterior wall to the right lateral wall; the mass was ulcerated and tethered. Anoscopy revealed a friable mass on the right side, starting just above the dentate line. A complete blood count and blood levels of urea nitrogen, creatinine, and carcinoembryonic antigen were normal.

Dr. Hong: A diagnostic procedure was performed, and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 74-year-old man with a history of prostate cancer that had been treated with brachytherapy was seen in an outpatient clinic of this hospital because of rectal bleeding of 6 months’ duration.

The patient had been well until approximately 6 months before the current evaluation, when he noted small amounts of fresh red blood with defecation. The blood was not mixed with the stool. Two months before this evaluation, the caliber of his stool decreased.

On evaluation, the patient reported daily bowel movements and no abdominal pain or weight loss. He had had a normal colonoscopy 3 years earlier, and he had no history of rectal or abdominal surgery. Nine years before this evaluation, an elevated level of prostate-specific antigen had been noted on routine screening, and a biopsy of the prostate had been performed.

Figure 1.

Biopsy Specimens and Colonoscopy Findings.
Dr. Lawrence R. Zukerberg: Five core-biopsy specimens had been procured from each side of the prostate (Figure 1A). Cancer was present in four of the five specimens from the right side and one of the five specimens from the left side. Both sides contained moderately differentiated adenocarcinoma, with a Gleason grade of 3 and a Gleason score of 6. Prostate cancer is graded with the use of the Gleason grading and scoring system. Gleason grades range from 1 to 5, with higher grades indicating more aggressive disease; most prostate cancers are Gleason grade 3, as in this case. More than one grade of cancer may be present in a biopsy sample. An overall Gleason score is calculated by adding two Gleason grades, the most extensive grade detected and the highest grade detected; in this case, specimens from both sides had a Gleason score of 6 (3 plus 3).

Dr. Hong: Imaging studies obtained at that time revealed no evidence of metastases. The patient was treated with iodine-125 brachytherapy (at a total dose of 144 Gy).

The patient also had hyperlipidemia, obesity, and multiple actinic keratoses and had undergone excision of several cutaneous squamous-cell and basal-cell carcinomas. Medications were atorvastatin and aspirin (81 mg daily). He had no known allergies, and he drank alcohol occasionally and did not smoke tobacco. He was retired and lived alone and had previously worked in an office position. A sister had died in her 70s of cancer, and another sister had died at 69 years of age of non-Hodgkin’s lymphoma.

On examination, the patient appeared well. He had a systolic murmur (grade 2/6), small external hemorrhoids, and mild-to-moderate abdominal adiposity with no tenderness, masses, or organomegaly. The inguinal regions were normal on palpation, with no inguinal lymphadenopathy. The pedal pulses were normal, and there was no leg edema. Digital rectal examination revealed a firm mass in the lower right lateral rectum that started 1 cm from the anal verge and extended 4 cm proximally from the posterior wall to the right lateral wall; the mass was ulcerated and tethered. Anoscopy revealed a friable mass on the right side, starting just above the dentate line. A complete blood count and blood levels of urea nitrogen, creatinine, and carcinoembryonic antigen were normal.

Dr. Hong: A diagnostic procedure was performed, and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Radiation Proctitis\n\nThe patient has a history of prostate cancer treated with brachytherapy, which involves the use of radiation. He presents with rectal bleeding and a decrease in stool caliber, which are common symptoms of radiation proctitis. This condition is a common complication of radiation therapy to the pelvic area, as the rectum is often unavoidably exposed to some radiation during the treatment of pelvic tumors. The physical examination findings of a firm, ulcerated mass in the rectum further support this diagnosis.""
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        ""role"": ""assistant"",
        ""content"": ""The patient has a history of prostate cancer treated with brachytherapy and is now presenting with rectal bleeding and a decrease in stool caliber. On examination, a firm, ulcerated mass was found in the lower right lateral rectum. These findings suggest a rectal mass, likely a rectal cancer. The history of prostate cancer treated with brachytherapy is relevant as radiation therapy can increase the risk of secondary malignancies, including rectal cancer. \n\nRectal Cancer""
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}",Rectal Cance,N,"{
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        ""role"": ""assistant"",
        ""content"": ""The patient is a 74-year-old man with a history of prostate cancer treated with brachytherapy who presents with rectal bleeding and a decrease in stool caliber. The differential diagnosis for this patient includes hemorrhoids, anal fissure, colorectal cancer, and radiation proctitis. Hemorrhoids and anal fissure are less likely given the presence of a firm, ulcerated mass in the rectum on digital rectal examination. Colorectal cancer is a possibility, especially given the patient's age and the presence of a rectal mass. However, the patient had a normal colonoscopy three years ago, which makes colorectal cancer less likely but does not rule it out. Radiation proctitis, inflammation and damage to the lower part of the colon after radiation therapy to the pelvic area, is also a possibility given the patient's history of brachytherapy for prostate cancer. The presence of a rectal mass could be due to a stricture or ulceration caused by radiation proctitis. \n\nDiagnosis: \nRadiation Proctitis is the most likely diagnosis.""
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10.1056/NEJMcpc1610101,Case 38-2016 — A 52-Year-Old Woman with Recurrent Oligodendroglioma,,"Oligodendroglioma (World Health Organization grade II out of IV), with an elevated Ki-67 proliferation index, an IDH1 R132H mutation, and codeletion of 1p and 19q.","Oligodendroglioma (World Health Organization grade II out of IV), with an elevated Ki-67 proliferation index, an IDH1 R132H mutation, and codeletion of 1p and 19q.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 52-year-old woman with a history of oligodendroglioma was seen in the outpatient neuro-oncology clinic of this hospital for routine follow-up.

Twelve years earlier, the patient presented with a generalized tonic–clonic seizure 4 days after she had undergone a cesarean section. Magnetic resonance imaging (MRI) performed at that time revealed an expansile, nonenhancing lesion in the anterior left frontal lobe. Pathological examination of a brain-biopsy specimen revealed evidence of oligodendroglioma (World Health Organization [WHO] grade II out of IV). A left frontotemporal craniotomy with resection of the tumor was performed; pathological examination of the resection specimen confirmed the presence of a WHO grade II oligodendroglioma with infiltration of the surrounding white matter. Results of postoperative MRI of the head suggested the presence of a residual tumor that extended into the right side of the genu of the corpus callosum. No adjuvant therapy was administered. The patient was monitored thereafter with serial MRI.

On the current evaluation, the patient reported persistent fatigue and mild problems with short-term memory that had not changed over time, with no seizures. On further questioning, she reported that 17 years earlier, 5 years before she received the diagnosis of oligodendroglioma, she had had a traumatic subdural hematoma that required evacuation, followed by a brief episode of arm and leg weakness and difficulty speaking. Phenytoin was administered for 6 months, and there were no recurrent events after it was discontinued. She had asthma. Her only current medication was carbamazepine. She had no known allergies. She lived with her husband and children. She did not smoke, drink alcohol, or use illicit drugs. Her mother (who had died) had had cancer involving lymph nodes and had received chemotherapy, a sister (who was living) had had a tumor of unknown type that was removed from her neck, and a daughter had attention deficit–hyperactivity disorder. There was also a family history of hypothyroidism.

The physical examination was normal. The blood level of alkaline phosphatase was 119 U per liter (reference range, 30 to 100); a complete blood count and results of other routine laboratory tests were normal. A review of all previous imaging studies of the head was requested, and the patient was referred for neurosurgical evaluation.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 52-year-old woman with a history of oligodendroglioma was seen in the outpatient neuro-oncology clinic of this hospital for routine follow-up.

Twelve years earlier, the patient presented with a generalized tonic–clonic seizure 4 days after she had undergone a cesarean section. Magnetic resonance imaging (MRI) performed at that time revealed an expansile, nonenhancing lesion in the anterior left frontal lobe. Pathological examination of a brain-biopsy specimen revealed evidence of oligodendroglioma (World Health Organization [WHO] grade II out of IV). A left frontotemporal craniotomy with resection of the tumor was performed; pathological examination of the resection specimen confirmed the presence of a WHO grade II oligodendroglioma with infiltration of the surrounding white matter. Results of postoperative MRI of the head suggested the presence of a residual tumor that extended into the right side of the genu of the corpus callosum. No adjuvant therapy was administered. The patient was monitored thereafter with serial MRI.

On the current evaluation, the patient reported persistent fatigue and mild problems with short-term memory that had not changed over time, with no seizures. On further questioning, she reported that 17 years earlier, 5 years before she received the diagnosis of oligodendroglioma, she had had a traumatic subdural hematoma that required evacuation, followed by a brief episode of arm and leg weakness and difficulty speaking. Phenytoin was administered for 6 months, and there were no recurrent events after it was discontinued. She had asthma. Her only current medication was carbamazepine. She had no known allergies. She lived with her husband and children. She did not smoke, drink alcohol, or use illicit drugs. Her mother (who had died) had had cancer involving lymph nodes and had received chemotherapy, a sister (who was living) had had a tumor of unknown type that was removed from her neck, and a daughter had attention deficit–hyperactivity disorder. There was also a family history of hypothyroidism.

The physical examination was normal. The blood level of alkaline phosphatase was 119 U per liter (reference range, 30 to 100); a complete blood count and results of other routine laboratory tests were normal. A review of all previous imaging studies of the head was requested, and the patient was referred for neurosurgical evaluation.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Oligodendroglioma recurrence. The patient has a history of oligodendroglioma and is presenting with persistent fatigue and mild problems with short-term memory. These symptoms, along with the fact that postoperative MRI suggested the presence of a residual tumor, suggest that the oligodendroglioma may have recurred.""
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        ""role"": ""assistant"",
        ""content"": ""The patient has a history of oligodendroglioma, a type of brain tumor. She presented with persistent fatigue and mild problems with short-term memory, which are common symptoms in patients with brain tumors. The patient also reported a history of a traumatic subdural hematoma, which could potentially increase the risk of developing brain tumors. The patient's physical examination was normal, and her blood level of alkaline phosphatase was slightly elevated, which can be associated with certain types of cancer, including brain tumors. The patient was referred for neurosurgical evaluation, which suggests that the medical team suspects a recurrence or progression of her brain tumor.\n\nDiagnosis: Recurrence of oligodendroglioma.""
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}",Recurrence of oligodendroglioma,Y,"{
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        ""role"": ""assistant"",
        ""content"": ""The patient is a 52-year-old woman with a history of oligodendroglioma, a type of brain tumor. She presents with persistent fatigue and mild problems with short-term memory, which are common symptoms in patients with brain tumors. However, these symptoms have not changed over time, suggesting that the tumor may not be growing. The patient also has a history of a traumatic subdural hematoma, which could potentially cause similar symptoms. However, this event occurred 17 years ago and the patient has not had any recurrent events since then, making it less likely to be the cause of her current symptoms. The patient's blood level of alkaline phosphatase is slightly elevated, which can be a sign of liver disease, bone disease, or certain types of cancer. However, the patient does not have any symptoms of liver or bone disease, and her complete blood count and other routine laboratory tests are normal. Given the patient's history and symptoms, the most likely diagnosis is a recurrence or progression of her oligodendroglioma. However, further imaging studies are needed to confirm this diagnosis.\n\nDiagnosis: Recurrence of oligodendroglioma.""
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10.1056/NEJMcpc1509539,Case 37-2016 — An 86-Year-Old Woman with Leukocytosis and Splenomegaly,,"Chronic neutrophilic leukemia, with a CSF3R mutation.",Chronic neutrophilic leukemia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
An 86-year-old woman was seen in the outpatient clinic of the cancer center at this hospital because of fatigue, night sweats, leukocytosis, and splenomegaly.

Table 1.

Laboratory Data.
The patient had a history of hypothyroidism and Lyme disease but was otherwise well until approximately 3 months before presentation, when progressive fatigue developed while she was traveling during the summer. Two months before presentation, she was seen by her physician at another hospital. On examination, the blood pressure was 170/80 mm Hg; the remainder of the examination was normal. The thyrotropin level was 7.9 _U per milliliter (reference range, 0.34 to 4.82); testing for Lyme disease was negative, and the creatine kinase level was normal. The patient’s dose of levothyroxine was increased from 50 _g to 75 _g daily. One week later, generalized unsteadiness developed. Computed tomography (CT) of the head, performed without the use of intravenous contrast material, showed no evidence of intracranial mass, hemorrhage, or infarct and was unchanged from imaging studies obtained 1 year earlier. Approximately 1 month before the current evaluation, fatigue markedly worsened, and diffuse muscle aches developed, which were associated with pain that radiated down both legs. Nine days before this evaluation, the patient went to the emergency department at the other hospital. On examination, the temperature was 36.9°C, the blood pressure 150/69 mm Hg, the pulse 67 beats per minute, the respiration rate 16 breaths per minute, and the oxygen saturation 95% while she was breathing ambient air. The erythrocyte sedimentation rate was normal, as were blood levels of electrolytes, glucose, total bilirubin, alanine aminotransferase, total protein, and albumin; results of renal function tests were also normal. Other test results are shown in Table 1. Blood cultures were obtained, and doxycycline was administered. The patient was advised that her symptoms were not consistent with Lyme disease and was instructed to see her primary care physician for further evaluation.

Four days later, on examination at her physician’s office, the patient reported recent night sweats that were so drenching that she had had to change her nightgown. On examination, the blood pressure was 141/69 mm Hg, and the abdomen was soft and slightly distended; the remainder of the examination was normal. Levels of total protein, albumin, total bilirubin, and direct bilirubin were normal; additional test results are shown in Table 1.

Figure 1.

Computed Tomographic Image of the Abdomen and Pelvis.
Dr. Naveen M. Kulkarni: The next day, CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed dependent atelectatic changes in both lungs (Figure 1), a low-attenuation lesion (measuring 15 mm in diameter) that was consistent with a hepatic cyst (with no biliary-duct dilatation), splenomegaly (maximal span, 15 cm [normal span, ≤13]), a renal cyst that appeared to be benign, atherosclerotic calcifications, and osteopenia. No evidence of metastatic disease in the abdomen or pelvis was seen.

Dr. Pearl: The patient was referred to the cancer center at this hospital.

On evaluation, she reported feeling tired and having intermittent muscle aches and night sweats. She reported no abnormal bleeding, bruising, shortness of breath, cough, chest pain, change in appetite or sleeping pattern, weight loss, rash, pruritus, or known recent tick bite. She had hypertension, hyperlipidemia, hypothyroidism, glaucoma, a history of babesiosis, and a history of recurrent urinary tract infections; she also reported having had depression after the death of her husband. A diagnosis of Lyme disease had been made 14 months earlier, when she presented with erythema migrans and fatigue. Doxycycline (100 mg twice daily for a period of 2 weeks) was administered, and the rash resolved. Two months later, body aches and night sweats developed but resolved after a brief period; testing for antibodies to Borrelia burgdorferi and polymerase-chain-reaction assays for Babesia microti and Anaplasma phagocytophilum nucleic acids were negative; other test results are shown in Table 1. She had had a hysterectomy for uterine prolapse, unilateral oophorectomy after an ectopic pregnancy, lumbar laminectomy, partial colectomy for diverticulosis, and bilateral total knee replacement. Daily medications and supplements included aspirin (81 mg), losartan, atorvastatin, calcium (40 mg), levothyroxine, celecoxib (200 mg), vitamin D, a multivitamin, cranberry tablets, and latanoprost ophthalmic solution, as well as lorazepam (0.5 mg, as needed) at night. She had no known allergies to medications. She lived alone in a coastal area of New England and had retired after working in education. She was physically active. She drank two alcoholic beverages each evening, had stopped smoking more than 50 years earlier after casual use, and did not use illicit drugs. Her father and sister had died of lung cancer, and her mother had died when she was older than 90 years of age. Her adult children were healthy.

On examination, the patient looked younger than her stated age. The temperature was 37.1°C, the blood pressure 146/62 mm Hg, the pulse 86 beats per minute, the respiration rate 18 breaths per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 25.4. The tip of the spleen was felt 1 to 2 cm below the left costal margin, and there was trace edema in both ankles. There was no lymphadenopathy, and the remainder of the examination was normal. Results of tests of coagulation and renal function were normal, as were blood levels of magnesium, phosphorus, and uric acid. Additional test results are shown in Table 1.

A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
An 86-year-old woman was seen in the outpatient clinic of the cancer center at this hospital because of fatigue, night sweats, leukocytosis, and splenomegaly.

Table 1.

Laboratory Data.
The patient had a history of hypothyroidism and Lyme disease but was otherwise well until approximately 3 months before presentation, when progressive fatigue developed while she was traveling during the summer. Two months before presentation, she was seen by her physician at another hospital. On examination, the blood pressure was 170/80 mm Hg; the remainder of the examination was normal. The thyrotropin level was 7.9 _U per milliliter (reference range, 0.34 to 4.82); testing for Lyme disease was negative, and the creatine kinase level was normal. The patient’s dose of levothyroxine was increased from 50 _g to 75 _g daily. One week later, generalized unsteadiness developed. Computed tomography (CT) of the head, performed without the use of intravenous contrast material, showed no evidence of intracranial mass, hemorrhage, or infarct and was unchanged from imaging studies obtained 1 year earlier. Approximately 1 month before the current evaluation, fatigue markedly worsened, and diffuse muscle aches developed, which were associated with pain that radiated down both legs. Nine days before this evaluation, the patient went to the emergency department at the other hospital. On examination, the temperature was 36.9°C, the blood pressure 150/69 mm Hg, the pulse 67 beats per minute, the respiration rate 16 breaths per minute, and the oxygen saturation 95% while she was breathing ambient air. The erythrocyte sedimentation rate was normal, as were blood levels of electrolytes, glucose, total bilirubin, alanine aminotransferase, total protein, and albumin; results of renal function tests were also normal. Other test results are shown in Table 1. Blood cultures were obtained, and doxycycline was administered. The patient was advised that her symptoms were not consistent with Lyme disease and was instructed to see her primary care physician for further evaluation.

Four days later, on examination at her physician’s office, the patient reported recent night sweats that were so drenching that she had had to change her nightgown. On examination, the blood pressure was 141/69 mm Hg, and the abdomen was soft and slightly distended; the remainder of the examination was normal. Levels of total protein, albumin, total bilirubin, and direct bilirubin were normal; additional test results are shown in Table 1.

Figure 1.

Computed Tomographic Image of the Abdomen and Pelvis.
Dr. Naveen M. Kulkarni: The next day, CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed dependent atelectatic changes in both lungs (Figure 1), a low-attenuation lesion (measuring 15 mm in diameter) that was consistent with a hepatic cyst (with no biliary-duct dilatation), splenomegaly (maximal span, 15 cm [normal span, ≤13]), a renal cyst that appeared to be benign, atherosclerotic calcifications, and osteopenia. No evidence of metastatic disease in the abdomen or pelvis was seen.

Dr. Pearl: The patient was referred to the cancer center at this hospital.

On evaluation, she reported feeling tired and having intermittent muscle aches and night sweats. She reported no abnormal bleeding, bruising, shortness of breath, cough, chest pain, change in appetite or sleeping pattern, weight loss, rash, pruritus, or known recent tick bite. She had hypertension, hyperlipidemia, hypothyroidism, glaucoma, a history of babesiosis, and a history of recurrent urinary tract infections; she also reported having had depression after the death of her husband. A diagnosis of Lyme disease had been made 14 months earlier, when she presented with erythema migrans and fatigue. Doxycycline (100 mg twice daily for a period of 2 weeks) was administered, and the rash resolved. Two months later, body aches and night sweats developed but resolved after a brief period; testing for antibodies to Borrelia burgdorferi and polymerase-chain-reaction assays for Babesia microti and Anaplasma phagocytophilum nucleic acids were negative; other test results are shown in Table 1. She had had a hysterectomy for uterine prolapse, unilateral oophorectomy after an ectopic pregnancy, lumbar laminectomy, partial colectomy for diverticulosis, and bilateral total knee replacement. Daily medications and supplements included aspirin (81 mg), losartan, atorvastatin, calcium (40 mg), levothyroxine, celecoxib (200 mg), vitamin D, a multivitamin, cranberry tablets, and latanoprost ophthalmic solution, as well as lorazepam (0.5 mg, as needed) at night. She had no known allergies to medications. She lived alone in a coastal area of New England and had retired after working in education. She was physically active. She drank two alcoholic beverages each evening, had stopped smoking more than 50 years earlier after casual use, and did not use illicit drugs. Her father and sister had died of lung cancer, and her mother had died when she was older than 90 years of age. Her adult children were healthy.

On examination, the patient looked younger than her stated age. The temperature was 37.1°C, the blood pressure 146/62 mm Hg, the pulse 86 beats per minute, the respiration rate 18 breaths per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 25.4. The tip of the spleen was felt 1 to 2 cm below the left costal margin, and there was trace edema in both ankles. There was no lymphadenopathy, and the remainder of the examination was normal. Results of tests of coagulation and renal function were normal, as were blood levels of magnesium, phosphorus, and uric acid. Additional test results are shown in Table 1.

A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Chronic Myeloid Leukemia (CML). The patient's symptoms of fatigue, night sweats, leukocytosis, and splenomegaly are all indicative of a hematological malignancy. The absence of lymphadenopathy and the presence of splenomegaly suggest a myeloproliferative disorder rather than a lymphoproliferative disorder. The patient's age also makes CML a more likely diagnosis, as it typically presents in older adults. The leukocytosis with a left shift (increased immature white blood cells) seen in the patient's lab results is characteristic of CML.""
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        ""role"": ""assistant"",
        ""content"": ""Chronic Myeloid Leukemia (CML)\nThe patient's symptoms of fatigue, night sweats, and splenomegaly, along with the laboratory findings of leukocytosis (high white blood cell count) are indicative of a hematological disorder. The presence of splenomegaly is often associated with diseases that involve abnormal proliferation of blood cells, such as leukemia. The patient's age also fits the typical age range for Chronic Myeloid Leukemia (CML), which is most commonly diagnosed in older adults. The absence of lymphadenopathy and the normal coagulation tests rule out some other types of leukemia. Therefore, the most likely diagnosis is Chronic Myeloid Leukemia.""
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}",Chronic Myeloid Leukemi,Y,"{
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        ""content"": ""The patient is an elderly woman presenting with fatigue, night sweats, leukocytosis, and splenomegaly. The differential diagnosis for these symptoms includes infections, malignancies, and autoimmune diseases. Given her history of Lyme disease, a recurrent infection could be considered, but her Lyme disease tests were negative. Her symptoms of fatigue and night sweats could be indicative of a malignancy, particularly a hematologic malignancy given her leukocytosis and splenomegaly. Autoimmune diseases could also present with these symptoms, but there is no mention of joint pain, rash, or other common autoimmune symptoms. The patient's age and the presence of splenomegaly and leukocytosis make a hematologic malignancy such as leukemia or lymphoma the most likely diagnosis.\n\nDiagnosis: Hematologic malignancy, likely leukemia or lymphoma.""
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10.1056/NEJMcpc1610099,Case 36-2016 — A 50-Year-Old Man with Acute Liver Injury,,Acute HEV infection.,Acute viral hepatitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 50-year-old man was admitted to this hospital because of elevated levels of serum aminotransferases, hyperbilirubinemia, anemia, and acute kidney injury.

The patient had been well until 6 days before admission, when fatigue and malaise developed. The next day, he had multiple episodes of nonbloody, nonbilious vomiting, accompanied by abdominal distention and diffuse abdominal pain. He felt feverish, but his temperature was 35.5°C. He took an unknown nonprescription medication for pain and one dose of ciprofloxacin that was provided by a family member. Three days before admission, his family noted yellowing of the skin and eyes and brought him to the emergency department of another hospital for evaluation.

Table 1.

Laboratory Data.
On examination in the emergency department, the temperature was 36.7°C, the blood pressure 122/81 mm Hg, the pulse 71 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 92% while the patient was breathing ambient air. He was alert and oriented and had no asterixis. The skin was jaundiced, the sclerae were icteric, and the abdomen was protuberant and not tender. The remainder of the examination was normal. The blood level of acetaminophen was less than 3 _g per milliliter (reference range, 10 to 25), and tests for hepatitis A virus (HAV) IgM antibodies, hepatitis B virus (HBV) surface antigen, hepatitis B virus (HBV) core IgM antibodies, hepatitis C virus (HCV) antibodies, and human immunodeficiency virus (HIV) type 1 (HIV-1) p24 antigen and HIV-1 and HIV-2 antibodies were negative; other laboratory test results are shown in Table 1. An interferon-gamma release assay for Mycobacterium tuberculosis was performed, and an abdominal ultrasound was obtained.

Figure 1.

Ultrasonography of the Abdomen.
Dr. Stephen R. Lee: Ultrasonography of the abdomen revealed a patent portal vein and coarse and heterogeneous echotexture of the liver, with no focal lesions. The gallbladder was contracted, with a thickened wall and biliary sludge (Figure 1); there were no gallstones, and testing for a sonographic Murphy’s sign was negative. The renal parenchyma was echogenic in both kidneys.

Dr. Ufere: N-acetylcysteine was administered, and the patient was admitted to the hospital. Nausea and intermittent vomiting persisted; a nonproductive cough developed, but the patient remained afebrile. The oxygen saturation, as measured by means of a pulse oximeter placed on the finger, was intermittently as low as 85%, and supplemental oxygen, adjusted to a rate of 2 to 4 liters per minute to ensure adequate oxygenation, was administered through a nasal cannula. On the second hospital day, computed tomography of the chest, performed after the intravenous administration of contrast material to assess for the presence of a pulmonary embolism, showed trace pleural effusion in the right lung and dependent atelectasis in both lungs, without evidence of pulmonary embolism. The arterial oxygen saturation, as measured by arterial blood gas testing, was greater than 99%, despite low peripheral oxygen saturation levels measured by a pulse oximeter on the finger. On the third hospital day, acute kidney injury developed, the degree of anemia worsened, and the patient was transferred to the medical intensive care unit. Examination of a peripheral-blood smear revealed anisocytosis, burr cells, spur cells, very few schistocytes, nucleated red cells, and polymorphonuclear cells with toxic granulation. A direct antiglobulin test was negative; other laboratory test results are shown in Table 1. Two units of packed red cells were transfused, piperacillin–tazobactam was administered, and the patient was transferred by ambulance to the medical intensive care unit of this hospital.

On admission, the patient reported occasional dark stools and mild, diffuse abdominal pain exacerbated by deep breaths. He had hyperlipidemia, and 7 months before admission he had taken an unknown cholesterol-lowering medication for a period of 2 months. He currently took no medications, herbal supplements, or Ayurvedic therapies. He last drank alcohol 6 months before admission, but he previously drank in a binge pattern, consuming 8 to 10 alcoholic drinks at a time, several days per month. He resided in a rural community in northern India, worked as a horticulturalist, and had cattle on his property. Two weeks before admission, he had traveled to New England to visit his pregnant daughter. Before traveling, he had attended several weddings in northern India, where the meals were shared among the guests, but he had had no known contact with persons who were ill. The patient’s father had reportedly died of an unspecified form of liver disease in his sixth decade of life.

On examination, the temperature was 36.9°C, the blood pressure 138/82 mm Hg, the pulse 90 beats per minute, the respiratory rate 14 breaths per minute, and the oxygen saturation 94% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 4 liters per minute. He was alert and oriented and had no dysarthria or asterixis. The skin was jaundiced, and the sclerae were icteric. The skin was without spider angiomas or palmar erythema. The first and second heart sounds were normal and without murmurs, and the jugular venous pulsation was not distended. Bowel sounds were present, and the abdomen was soft and mildly distended, with minimally diffuse tenderness to palpation. The liver edge was palpable and nontender, with no splenomegaly. There was no edema in his arms or legs. Rectal examination revealed brown stool that tested positive for fecal occult blood. Urinalysis showed 2+ glucose, 2+ bilirubin, 2+ blood, 2+ protein, a specific gravity of 1.010 (reference range, 1.001 to 1.035), and a pH of 7 (reference range, 5 to 9). In a random urine sample, the urinary sodium level was 67 mmol per liter, and the urinary creatinine level was 36 mg per deciliter. Other test results are shown in Table 1. Additional imaging studies were obtained.

Figure 2.

Magnetic Resonance Imaging of the Abdomen.
Dr. Lee: Magnetic resonance imaging of the abdomen performed after the administration of gadolinium showed mild changes suggestive of diffuse hepatic steatosis, a contracted gallbladder with gallbladder-wall edema, and fluid and fat stranding surrounding the second and third portions of the duodenum; the portal vein was not well visualized (Figure 2).

Dr. Ufere: N-acetylcysteine and piperacillin–tazobactam were continued. Nephrology and hepatology consultations were obtained. Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 50-year-old man was admitted to this hospital because of elevated levels of serum aminotransferases, hyperbilirubinemia, anemia, and acute kidney injury.

The patient had been well until 6 days before admission, when fatigue and malaise developed. The next day, he had multiple episodes of nonbloody, nonbilious vomiting, accompanied by abdominal distention and diffuse abdominal pain. He felt feverish, but his temperature was 35.5°C. He took an unknown nonprescription medication for pain and one dose of ciprofloxacin that was provided by a family member. Three days before admission, his family noted yellowing of the skin and eyes and brought him to the emergency department of another hospital for evaluation.

Table 1.

Laboratory Data.
On examination in the emergency department, the temperature was 36.7°C, the blood pressure 122/81 mm Hg, the pulse 71 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 92% while the patient was breathing ambient air. He was alert and oriented and had no asterixis. The skin was jaundiced, the sclerae were icteric, and the abdomen was protuberant and not tender. The remainder of the examination was normal. The blood level of acetaminophen was less than 3 _g per milliliter (reference range, 10 to 25), and tests for hepatitis A virus (HAV) IgM antibodies, hepatitis B virus (HBV) surface antigen, hepatitis B virus (HBV) core IgM antibodies, hepatitis C virus (HCV) antibodies, and human immunodeficiency virus (HIV) type 1 (HIV-1) p24 antigen and HIV-1 and HIV-2 antibodies were negative; other laboratory test results are shown in Table 1. An interferon-gamma release assay for Mycobacterium tuberculosis was performed, and an abdominal ultrasound was obtained.

Figure 1.

Ultrasonography of the Abdomen.
Dr. Stephen R. Lee: Ultrasonography of the abdomen revealed a patent portal vein and coarse and heterogeneous echotexture of the liver, with no focal lesions. The gallbladder was contracted, with a thickened wall and biliary sludge (Figure 1); there were no gallstones, and testing for a sonographic Murphy’s sign was negative. The renal parenchyma was echogenic in both kidneys.

Dr. Ufere: N-acetylcysteine was administered, and the patient was admitted to the hospital. Nausea and intermittent vomiting persisted; a nonproductive cough developed, but the patient remained afebrile. The oxygen saturation, as measured by means of a pulse oximeter placed on the finger, was intermittently as low as 85%, and supplemental oxygen, adjusted to a rate of 2 to 4 liters per minute to ensure adequate oxygenation, was administered through a nasal cannula. On the second hospital day, computed tomography of the chest, performed after the intravenous administration of contrast material to assess for the presence of a pulmonary embolism, showed trace pleural effusion in the right lung and dependent atelectasis in both lungs, without evidence of pulmonary embolism. The arterial oxygen saturation, as measured by arterial blood gas testing, was greater than 99%, despite low peripheral oxygen saturation levels measured by a pulse oximeter on the finger. On the third hospital day, acute kidney injury developed, the degree of anemia worsened, and the patient was transferred to the medical intensive care unit. Examination of a peripheral-blood smear revealed anisocytosis, burr cells, spur cells, very few schistocytes, nucleated red cells, and polymorphonuclear cells with toxic granulation. A direct antiglobulin test was negative; other laboratory test results are shown in Table 1. Two units of packed red cells were transfused, piperacillin–tazobactam was administered, and the patient was transferred by ambulance to the medical intensive care unit of this hospital.

On admission, the patient reported occasional dark stools and mild, diffuse abdominal pain exacerbated by deep breaths. He had hyperlipidemia, and 7 months before admission he had taken an unknown cholesterol-lowering medication for a period of 2 months. He currently took no medications, herbal supplements, or Ayurvedic therapies. He last drank alcohol 6 months before admission, but he previously drank in a binge pattern, consuming 8 to 10 alcoholic drinks at a time, several days per month. He resided in a rural community in northern India, worked as a horticulturalist, and had cattle on his property. Two weeks before admission, he had traveled to New England to visit his pregnant daughter. Before traveling, he had attended several weddings in northern India, where the meals were shared among the guests, but he had had no known contact with persons who were ill. The patient’s father had reportedly died of an unspecified form of liver disease in his sixth decade of life.

On examination, the temperature was 36.9°C, the blood pressure 138/82 mm Hg, the pulse 90 beats per minute, the respiratory rate 14 breaths per minute, and the oxygen saturation 94% while the patient was receiving supplemental oxygen through a nasal cannula at a rate of 4 liters per minute. He was alert and oriented and had no dysarthria or asterixis. The skin was jaundiced, and the sclerae were icteric. The skin was without spider angiomas or palmar erythema. The first and second heart sounds were normal and without murmurs, and the jugular venous pulsation was not distended. Bowel sounds were present, and the abdomen was soft and mildly distended, with minimally diffuse tenderness to palpation. The liver edge was palpable and nontender, with no splenomegaly. There was no edema in his arms or legs. Rectal examination revealed brown stool that tested positive for fecal occult blood. Urinalysis showed 2+ glucose, 2+ bilirubin, 2+ blood, 2+ protein, a specific gravity of 1.010 (reference range, 1.001 to 1.035), and a pH of 7 (reference range, 5 to 9). In a random urine sample, the urinary sodium level was 67 mmol per liter, and the urinary creatinine level was 36 mg per deciliter. Other test results are shown in Table 1. Additional imaging studies were obtained.

Figure 2.

Magnetic Resonance Imaging of the Abdomen.
Dr. Lee: Magnetic resonance imaging of the abdomen performed after the administration of gadolinium showed mild changes suggestive of diffuse hepatic steatosis, a contracted gallbladder with gallbladder-wall edema, and fluid and fat stranding surrounding the second and third portions of the duodenum; the portal vein was not well visualized (Figure 2).

Dr. Ufere: N-acetylcysteine and piperacillin–tazobactam were continued. Nephrology and hepatology consultations were obtained. Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Acute liver failure due to mushroom poisoning. The patient's symptoms of elevated aminotransferases, hyperbilirubinemia, anemia, and acute kidney injury, along with his history of residing in a rural community and working as a horticulturalist, suggest the possibility of mushroom poisoning. This is further supported by the fact that his symptoms began after attending several weddings where meals were shared, as certain toxic mushrooms can cause these symptoms if ingested. The negative tests for viral hepatitis and the lack of improvement with antibiotics also support a non-infectious cause such as mushroom poisoning.""
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        ""content"": ""The patient presents with elevated levels of serum aminotransferases, hyperbilirubinemia, anemia, and acute kidney injury. He also has jaundice, fatigue, malaise, vomiting, abdominal distention and pain, and intermittent low oxygen saturation. His liver shows diffuse hepatic steatosis and his gallbladder is contracted with wall edema. His symptoms and the imaging findings suggest liver disease. The patient's history of binge drinking could have contributed to alcoholic liver disease, but he stopped drinking 6 months ago. His recent travel to India and shared meals at weddings could suggest a possible infectious cause, but tests for hepatitis A, B, and C were negative. The patient's father reportedly died of liver disease, suggesting a possible genetic component. The patient's symptoms, lab findings, and imaging results are consistent with acute liver failure, possibly due to drug-induced liver injury from the unknown nonprescription medication and ciprofloxacin he took shortly before his symptoms began.\n\nDiagnosis: Acute liver failure, likely due to drug-induced liver injury.""
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        ""content"": ""The patient is a 50-year-old man presenting with elevated levels of serum aminotransferases, hyperbilirubinemia, anemia, and acute kidney injury. He also has symptoms of fatigue, malaise, vomiting, abdominal distention and pain, and jaundice. The differential diagnosis for this patient includes acute hepatitis, alcoholic liver disease, drug-induced liver injury, and hemolytic anemia. The patient's tests for hepatitis A, B, C, and HIV were all negative, making acute hepatitis less likely. The patient's history of binge drinking could suggest alcoholic liver disease, but he last drank alcohol 6 months ago, making this less likely. The patient took an unknown nonprescription medication for pain and one dose of ciprofloxacin, which could potentially cause drug-induced liver injury. However, the patient's blood level of acetaminophen was less than 3 _g per milliliter, which is below the reference range, making drug-induced liver injury less likely. The patient's anemia worsened and examination of a peripheral-blood smear revealed anisocytosis, burr cells, spur cells, very few schistocytes, nucleated red cells, and polymorphonuclear cells with toxic granulation, which could suggest hemolytic anemia. However, a direct antiglobulin test was negative, making hemolytic anemia less likely. The patient's father reportedly died of an unspecified form of liver disease, which could suggest a genetic liver disease. The patient's imaging showed changes suggestive of diffuse hepatic steatosis, a contracted gallbladder with gallbladder-wall edema, and fluid and fat stranding surrounding the second and third portions of the duodenum, which could suggest acute cholangitis. However, the patient's portal vein was not well visualized, making acute cholangitis less likely. The patient's symptoms and test results are most consistent with acute liver failure.\n\nDiagnosis: Acute liver failure.""
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10.1056/NEJMcpc1610714,Case 35-2016 — A 62-Year-Old Man with Dysphagia,,"Poorly differentiated, metastatic esophageal adenocarcinoma with MET amplification and a PIK3CA mutation.","Poorly differentiated, metastatic esophageal adenocarcinoma with MET amplification and a PIK3CA mutation.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 62-year-old man was seen in the outpatient oncology clinic of this hospital because of metastatic esophageal adenocarcinoma.

Approximately 2 months before this presentation, the patient noted discomfort in his throat that he described as a “golf ball.” Pantoprazole was administered for possible gastroesophageal reflux disease, but his condition did not improve. Six weeks later, on evaluation in the outpatient gastroenterology clinic of this hospital, he reported that he had chronic nocturnal heartburn (pyrosis) and that, during the previous month, he had had the sensation of food sitting in his upper chest, decreased oral intake, and intermittent vomiting.

Figure 1.

Barium Swallow and Imaging Studies.
Dr. Avinash Kambadakone: One week later, a barium swallow examination (Figure 1A) revealed an annular constriction (3 to 4 cm in length) with irregular mucosal contours involving the distal esophagus and gastroesophageal junction, a finding suggestive of esophageal cancer. Two days later, positron-emission tomography (PET) and computed tomography (CT) (Figure 1B and 1C) revealed a mass with intense 18F-fluorodeoxyglucose (FDG) uptake involving the distal esophagus and gastroesophageal junction, as well as lymphadenopathy with intense FDG uptake involving the mediastinal, retrocrural, and retroperitoneal regions. Extensive lymphadenopathy with moderately intense FDG uptake was present in the left axillary, paratracheal, hilar, subcarinal, and pericardiac regions.

Dr. Kwak: The white-cell count was 14,500 per cubic millimeter (reference range, 4500 to 11,000), the hematocrit 37.2% (reference range in men, 41.0 to 53.0), the hemoglobin level 13.2 g per deciliter (reference range in men, 13.5 to 17.5), the carcinoembryonic antigen level 42.3 ng per milliliter (reference value, <3.4), and the CA19-9 level 383 U per milliliter (reference value, <35). The platelet count, red-cell indexes, and results of coagulation and renal- and liver-function tests were normal, as were blood levels of electrolytes, glucose, total protein, albumin, globulin, lipase, and amylase.

Figure 2.

Endoscopy and Endoscopic Ultrasound Images.
Dr. David G. Forcione: Four days later, 2 days before the evaluation in the outpatient oncology clinic, upper endoscopy (Figure 2A) revealed an ulcerated luminal stricture in the distal esophagus that extended to the gastroesophageal junction (involving the area located between 39 cm and 44 cm from the incisors). Nodular tissue was heaped up around the ulcer base. Balloon dilation of the stricture to a 12-mm diameter (Figure 2B) was performed to facilitate passage of the endoscope to the stomach and duodenum, which appeared normal. Esophageal endoscopic ultrasonography, performed at a frequency of 5 MHz, revealed a transmural hypoechoic mass and multiple enlarged, round periesophageal lymph nodes measuring 6 mm to 19 mm in diameter (Figure 2C). A round perigastric node (measuring 20 mm in diameter) with homogeneous, hypoechoic features was identified and was highly suspicious for cancer (Figure 2D); there were no focal liver lesions, ascites, or pancreatobiliary lesions. On the basis of the findings on endoscopic ultrasonography, the patient had stage uT3N2Mx disease (defined according to the tumor–node–metastasis staging system of the American Joint Committee on Cancer). Biopsy and fine-needle aspiration were performed.

Figure 3.

Biopsy Specimens.
Dr. Jochen K. Lennerz: A biopsy sample of the esophageal mass and a fine-needle aspirate from the enlarged paragastric lymph node were obtained (Figure 3A through 3D). Pathological examination revealed evidence of a poorly differentiated adenocarcinoma that had metastasized to the lymph nodes, and this finding confirmed that the patient had at least stage pT1N1Mx disease.

Dr. Kwak: The patient was referred to the gastrointestinal oncology clinic of this hospital. He reported dysphagia, vomiting after some meals, decreased oral intake, and weight loss of 9 kg during the previous 2 months. He was able to consume soft solids and all liquids, and he reported some symptomatic improvement after the esophageal dilation was performed 2 days earlier.

The patient had hypertension, hypercholesterolemia, degenerative disk disease, and a history of diarrhea related to a partial small-bowel resection that had been performed when he was 11 years of age after he underwent an appendectomy and had subsequent small-bowel obstruction. He had had a transient ischemic attack and had undergone dental extractions, spinal laminectomies, and knee arthroplasty. Medications were aspirin, dipyridamole, atenolol, cholestyramine resin, lisinopril, hydrochlorothiazide, diphenoxylate–atropine, gemfibrozil, and tramadol. He had no known allergies. He smoked cigarettes (45 pack-years), drank alcohol in moderation, and did not use illicit drugs. He lived with his wife, daughter, and grandchildren. His father had died from heart disease at 45 years of age, and his mother had died from metastatic cancer (unknown primary) at 85 years of age; there was no family history of gastrointestinal diseases.

On examination, the vital signs were normal. The weight was 111 kg, and the remainder of the examination was normal. Oxycodone (for pain, as needed) and bupropion were administered.

Dr. Kambadakone: CT of the chest, abdomen, and pelvis revealed multiple small pulmonary nodules that were most likely pulmonary metastases. An indeterminate enhancing mass was seen in the lower pole of the right kidney.

Dr. Kwak: Management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 62-year-old man was seen in the outpatient oncology clinic of this hospital because of metastatic esophageal adenocarcinoma.

Approximately 2 months before this presentation, the patient noted discomfort in his throat that he described as a “golf ball.” Pantoprazole was administered for possible gastroesophageal reflux disease, but his condition did not improve. Six weeks later, on evaluation in the outpatient gastroenterology clinic of this hospital, he reported that he had chronic nocturnal heartburn (pyrosis) and that, during the previous month, he had had the sensation of food sitting in his upper chest, decreased oral intake, and intermittent vomiting.

Figure 1.

Barium Swallow and Imaging Studies.
Dr. Avinash Kambadakone: One week later, a barium swallow examination (Figure 1A) revealed an annular constriction (3 to 4 cm in length) with irregular mucosal contours involving the distal esophagus and gastroesophageal junction, a finding suggestive of esophageal cancer. Two days later, positron-emission tomography (PET) and computed tomography (CT) (Figure 1B and 1C) revealed a mass with intense 18F-fluorodeoxyglucose (FDG) uptake involving the distal esophagus and gastroesophageal junction, as well as lymphadenopathy with intense FDG uptake involving the mediastinal, retrocrural, and retroperitoneal regions. Extensive lymphadenopathy with moderately intense FDG uptake was present in the left axillary, paratracheal, hilar, subcarinal, and pericardiac regions.

Dr. Kwak: The white-cell count was 14,500 per cubic millimeter (reference range, 4500 to 11,000), the hematocrit 37.2% (reference range in men, 41.0 to 53.0), the hemoglobin level 13.2 g per deciliter (reference range in men, 13.5 to 17.5), the carcinoembryonic antigen level 42.3 ng per milliliter (reference value, <3.4), and the CA19-9 level 383 U per milliliter (reference value, <35). The platelet count, red-cell indexes, and results of coagulation and renal- and liver-function tests were normal, as were blood levels of electrolytes, glucose, total protein, albumin, globulin, lipase, and amylase.

Figure 2.

Endoscopy and Endoscopic Ultrasound Images.
Dr. David G. Forcione: Four days later, 2 days before the evaluation in the outpatient oncology clinic, upper endoscopy (Figure 2A) revealed an ulcerated luminal stricture in the distal esophagus that extended to the gastroesophageal junction (involving the area located between 39 cm and 44 cm from the incisors). Nodular tissue was heaped up around the ulcer base. Balloon dilation of the stricture to a 12-mm diameter (Figure 2B) was performed to facilitate passage of the endoscope to the stomach and duodenum, which appeared normal. Esophageal endoscopic ultrasonography, performed at a frequency of 5 MHz, revealed a transmural hypoechoic mass and multiple enlarged, round periesophageal lymph nodes measuring 6 mm to 19 mm in diameter (Figure 2C). A round perigastric node (measuring 20 mm in diameter) with homogeneous, hypoechoic features was identified and was highly suspicious for cancer (Figure 2D); there were no focal liver lesions, ascites, or pancreatobiliary lesions. On the basis of the findings on endoscopic ultrasonography, the patient had stage uT3N2Mx disease (defined according to the tumor–node–metastasis staging system of the American Joint Committee on Cancer). Biopsy and fine-needle aspiration were performed.

Figure 3.

Biopsy Specimens.
Dr. Jochen K. Lennerz: A biopsy sample of the esophageal mass and a fine-needle aspirate from the enlarged paragastric lymph node were obtained (Figure 3A through 3D). Pathological examination revealed evidence of a poorly differentiated adenocarcinoma that had metastasized to the lymph nodes, and this finding confirmed that the patient had at least stage pT1N1Mx disease.

Dr. Kwak: The patient was referred to the gastrointestinal oncology clinic of this hospital. He reported dysphagia, vomiting after some meals, decreased oral intake, and weight loss of 9 kg during the previous 2 months. He was able to consume soft solids and all liquids, and he reported some symptomatic improvement after the esophageal dilation was performed 2 days earlier.

The patient had hypertension, hypercholesterolemia, degenerative disk disease, and a history of diarrhea related to a partial small-bowel resection that had been performed when he was 11 years of age after he underwent an appendectomy and had subsequent small-bowel obstruction. He had had a transient ischemic attack and had undergone dental extractions, spinal laminectomies, and knee arthroplasty. Medications were aspirin, dipyridamole, atenolol, cholestyramine resin, lisinopril, hydrochlorothiazide, diphenoxylate–atropine, gemfibrozil, and tramadol. He had no known allergies. He smoked cigarettes (45 pack-years), drank alcohol in moderation, and did not use illicit drugs. He lived with his wife, daughter, and grandchildren. His father had died from heart disease at 45 years of age, and his mother had died from metastatic cancer (unknown primary) at 85 years of age; there was no family history of gastrointestinal diseases.

On examination, the vital signs were normal. The weight was 111 kg, and the remainder of the examination was normal. Oxycodone (for pain, as needed) and bupropion were administered.

Dr. Kambadakone: CT of the chest, abdomen, and pelvis revealed multiple small pulmonary nodules that were most likely pulmonary metastases. An indeterminate enhancing mass was seen in the lower pole of the right kidney.

Dr. Kwak: Management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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10.1056/NEJMcpc1610096,Case 34-2016 — A 17-Year-Old Boy with Myopia and Craniofacial and Skeletal Abnormalities,,Homocystinuria caused by cystathionine _-synthase deficiency.,Homocystinuria caused by cystathionine _-synthase deficiency.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 17-year-old boy was referred to the medical genetics clinic of this hospital because of high myopia (i.e., severe nearsightedness) and craniofacial and other skeletal abnormalities.

As a child, the patient had had difficulty with articulation and had received speech therapy. When he was approximately 12 years of age, dental crowding and class III dentofacial growth pattern were noted (class I growth pattern indicates normal development, class II indicates protrusion of the maxilla, and class III indicates protrusion of the mandible), and between 12 and 16 years of age, the patient had orthodontic braces and a palate expander. After the braces were removed, difficulty eating and chewing reportedly worsened. Eight weeks before this evaluation, he was referred to the outpatient Oral and Maxillofacial Surgery department at this hospital.

Figure 1.

Clinical Images.
Dr. Maria J. Troulis: On examination, the patient had frontal bossing, downward-slanted lateral canthi, symmetric hypoplasia of the midface and maxilla, and relative mandibular hyperplasia (i.e., hyperplasia of the mandible relative to the size of the maxilla and midface) (Figure 1A and 1B). There was a negative overjet of more than 10 mm (i.e., the mandibular teeth extended more than 10 mm horizontally beyond the maxillary teeth), and the lower teeth were retroclined. The ears were in a normal position, but they protruded outward. He was referred to the medical genetics clinic for evaluation of a possible genetic cause of these and other skeletal abnormalities.

Dr. Lin: The patient was born at full term by vaginal delivery; his birth weight was 4.3 kg. A pectus excavatum was present at birth. His height was at the 80th percentile until he was 15 years of age, after which it plateaued at the 55th percentile. No developmental delays were noted during childhood.

An intermittent systolic heart murmur, which was graded 3 out of 6 (with 1 indicating a soft murmur and 6 indicating a loud murmur) had first been noted when the patient was 13 years of age. Evaluations by three cardiologists during the next 4 years revealed no cardiovascular symptoms or decreased capacity; electrocardiograms showed an indeterminate axis, and echocardiographic studies reportedly revealed a normal aortic-root size and no evidence of anomalous vasculature, atrial septal defect, valvular structural abnormalities, or findings suggestive of Marfan’s syndrome. The murmur was thought to be turbulence related to the position of the heart in relation to the pectus deformity. On cardiogenetic examination performed at another hospital when the patient was 16 years of age, his weight was 69.2 kg, the height 177.8 cm, the arm span 188 cm, the ratio of arm span to height 1.06, and the ratio of upper to lower body segment 0.87. Pectus excavatum of the upper chest and pectus carinatum of the lower chest were seen, as were broad thumbs, with no evidence of joint hypermobility. Although there was insufficient evidence to diagnose Marfan’s syndrome, a connective tissue abnormality was suspected. He was referred to a medical geneticist, but his family acknowledged that they were focused on the craniofacial evaluation.

Dr. Teresa C. Chen: When the patient was 13 years of age, a diagnosis of myopia was made, and eyeglasses were prescribed by his optometrist. Over the course of the next 4 years, examinations performed at the optometrist’s office showed an increase of 12.75 diopters of myopia in the right eye and an increase of 11.00 diopters in the left eye. Nine months before this evaluation, his manifest refraction was reportedly _13.75 diopters in the right eye and _10.00 diopters in the left eye. Eight months before this evaluation, the patient was seen in the ophthalmology clinic at the Massachusetts Eye and Ear Infirmary.

On examination, his right eye refracted to a spherical equivalent of _14.50 diopters and his left eye refracted to a spherical equivalent of _11.00 diopters. Visual acuity was 20/20 in both eyes when the patient was wearing eyeglasses. The anterior chambers were shallow (Figure 1C), and the angles were open on gonioscopy. The lenses were rounder and smaller than normal, and the lens perimeters and zonules were clearly visible in both eyes after dilation (Figure 1D). The findings on ultrasound biomicroscopy were consistent with microspherophakia (small, spherically shaped lenses) (Fig. S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org), with lens diameters of 8.41 mm in the right eye and 8.03 mm in the left eye (normal diameter, >9 mm). Lens thickness values were 4.97 mm in each eye. Axial lengths were 24.15 mm in the right eye and 23.91 mm in the left eye. Ultrasonography confirmed shallow anterior chambers, with anterior chamber depths of 2.20 mm in the right eye and 2.82 mm in the left eye (normal depth, >3.00 mm).

Dr. Lin: The patient had had no serious childhood illnesses. He had bilateral epididymal cysts that had been stable for many years, had undergone repair of urethral meatal stenosis, had had an impacted fracture of the wrist owing to a sports-related injury when he was 12 years of age, and had transient musculoskeletal back pain. He was not taking any medications. He had received all routine childhood immunizations and was allergic to melons. He lived with his parents and brother, and he did well in school. He had never used tobacco, alcohol, or illicit drugs.

The patient’s brother, who was 3 years older than the patient, had a deep asymmetric pectus excavatum and a history of sports-related injuries, including several ankle injuries and recurrent avulsion of a hip joint associated with kicking. He did not wear eyeglasses and had no unusual facial features except for a mild underbite. The patient’s mother was of Irish and Italian ancestry, and his father was of Italian, Portuguese, Irish, and Scottish ancestry; there was no known consanguinity. His father and multiple paternal relatives had hypertension; his paternal grandfather had coronary artery disease, his grandmother had an endocrine brain tumor, his aunt had Crohn’s disease, and an uncle had arthritis. His mother was healthy, his maternal grandmother had non-Hodgkin’s lymphoma, and a cousin had celiac disease. His mother, maternal grandmother, and aunt were 165 cm tall; his brother and maternal grandfather were 170 cm tall; and his father was 175 cm tall.

On examination, the blood pressure and pulse were normal. The weight was 66.3 kg (48th percentile), the height 177.5 cm (58th percentile), and the head circumference 58.5 cm (98th percentile). There was slight frontal bossing. The conjunctivae were clear, and the sclerae were white, without blue or gray hue. There was a mixed chest-wall defect, with funnel-shaped pectus excavatum and lower sternal protrusion with protrusion of parasternal cartilages (Figure 1E and 1F). A harsh, grade 3 systolic murmur was heard at the upper sternal border, without systolic click or diastolic murmur. There was loss of the normal upper curvature of the spine, as well as scoliosis, with the scapula and rib cage on the right side higher than the left. The remainder of the examination was normal or unchanged from recent previous examinations. The patient had above-average intelligence and was reserved. He asked thoughtful questions and consented to the proposed evaluations.

Figure 2.

Imaging Studies.
Dr. Sjirk J. Westra: Radiographs of the skeleton, including hands and feet, showed straightening of the normal cervical lordosis, rotatory S-shaped dextroconvex thoracic scoliosis, and generalized osteoporosis, with biconcavity of the end plates of multiple vertebral bodies, also known as “fish” or “codfish” vertebrae (Figure 2A).1,2

A dual-energy x-ray absorptiometry scan (Figure 2B) revealed an abnormally low bone mineral density of 0.75 g per square centimeter averaged over vertebral bodies L1 through L4; when compared with age-matched controls, this value resulted in a z score of _2.7, which is indicative of osteoporosis.

Dr. Lin: The blood level of phosphorus was 4.7 mg per deciliter (reference range, 3.0 to 4.5), and the level of 25-hydroxyvitamin D was 19 ng per milliliter (desired level, >32). A complete blood count and blood levels of electrolytes, folic acid, vitamin B12, calcium, glucose, total protein, albumin, and globulin were normal. Tests of renal function were also normal.

Additional diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 17-year-old boy was referred to the medical genetics clinic of this hospital because of high myopia (i.e., severe nearsightedness) and craniofacial and other skeletal abnormalities.

As a child, the patient had had difficulty with articulation and had received speech therapy. When he was approximately 12 years of age, dental crowding and class III dentofacial growth pattern were noted (class I growth pattern indicates normal development, class II indicates protrusion of the maxilla, and class III indicates protrusion of the mandible), and between 12 and 16 years of age, the patient had orthodontic braces and a palate expander. After the braces were removed, difficulty eating and chewing reportedly worsened. Eight weeks before this evaluation, he was referred to the outpatient Oral and Maxillofacial Surgery department at this hospital.

Figure 1.

Clinical Images.
Dr. Maria J. Troulis: On examination, the patient had frontal bossing, downward-slanted lateral canthi, symmetric hypoplasia of the midface and maxilla, and relative mandibular hyperplasia (i.e., hyperplasia of the mandible relative to the size of the maxilla and midface) (Figure 1A and 1B). There was a negative overjet of more than 10 mm (i.e., the mandibular teeth extended more than 10 mm horizontally beyond the maxillary teeth), and the lower teeth were retroclined. The ears were in a normal position, but they protruded outward. He was referred to the medical genetics clinic for evaluation of a possible genetic cause of these and other skeletal abnormalities.

Dr. Lin: The patient was born at full term by vaginal delivery; his birth weight was 4.3 kg. A pectus excavatum was present at birth. His height was at the 80th percentile until he was 15 years of age, after which it plateaued at the 55th percentile. No developmental delays were noted during childhood.

An intermittent systolic heart murmur, which was graded 3 out of 6 (with 1 indicating a soft murmur and 6 indicating a loud murmur) had first been noted when the patient was 13 years of age. Evaluations by three cardiologists during the next 4 years revealed no cardiovascular symptoms or decreased capacity; electrocardiograms showed an indeterminate axis, and echocardiographic studies reportedly revealed a normal aortic-root size and no evidence of anomalous vasculature, atrial septal defect, valvular structural abnormalities, or findings suggestive of Marfan’s syndrome. The murmur was thought to be turbulence related to the position of the heart in relation to the pectus deformity. On cardiogenetic examination performed at another hospital when the patient was 16 years of age, his weight was 69.2 kg, the height 177.8 cm, the arm span 188 cm, the ratio of arm span to height 1.06, and the ratio of upper to lower body segment 0.87. Pectus excavatum of the upper chest and pectus carinatum of the lower chest were seen, as were broad thumbs, with no evidence of joint hypermobility. Although there was insufficient evidence to diagnose Marfan’s syndrome, a connective tissue abnormality was suspected. He was referred to a medical geneticist, but his family acknowledged that they were focused on the craniofacial evaluation.

Dr. Teresa C. Chen: When the patient was 13 years of age, a diagnosis of myopia was made, and eyeglasses were prescribed by his optometrist. Over the course of the next 4 years, examinations performed at the optometrist’s office showed an increase of 12.75 diopters of myopia in the right eye and an increase of 11.00 diopters in the left eye. Nine months before this evaluation, his manifest refraction was reportedly _13.75 diopters in the right eye and _10.00 diopters in the left eye. Eight months before this evaluation, the patient was seen in the ophthalmology clinic at the Massachusetts Eye and Ear Infirmary.

On examination, his right eye refracted to a spherical equivalent of _14.50 diopters and his left eye refracted to a spherical equivalent of _11.00 diopters. Visual acuity was 20/20 in both eyes when the patient was wearing eyeglasses. The anterior chambers were shallow (Figure 1C), and the angles were open on gonioscopy. The lenses were rounder and smaller than normal, and the lens perimeters and zonules were clearly visible in both eyes after dilation (Figure 1D). The findings on ultrasound biomicroscopy were consistent with microspherophakia (small, spherically shaped lenses) (Fig. S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org), with lens diameters of 8.41 mm in the right eye and 8.03 mm in the left eye (normal diameter, >9 mm). Lens thickness values were 4.97 mm in each eye. Axial lengths were 24.15 mm in the right eye and 23.91 mm in the left eye. Ultrasonography confirmed shallow anterior chambers, with anterior chamber depths of 2.20 mm in the right eye and 2.82 mm in the left eye (normal depth, >3.00 mm).

Dr. Lin: The patient had had no serious childhood illnesses. He had bilateral epididymal cysts that had been stable for many years, had undergone repair of urethral meatal stenosis, had had an impacted fracture of the wrist owing to a sports-related injury when he was 12 years of age, and had transient musculoskeletal back pain. He was not taking any medications. He had received all routine childhood immunizations and was allergic to melons. He lived with his parents and brother, and he did well in school. He had never used tobacco, alcohol, or illicit drugs.

The patient’s brother, who was 3 years older than the patient, had a deep asymmetric pectus excavatum and a history of sports-related injuries, including several ankle injuries and recurrent avulsion of a hip joint associated with kicking. He did not wear eyeglasses and had no unusual facial features except for a mild underbite. The patient’s mother was of Irish and Italian ancestry, and his father was of Italian, Portuguese, Irish, and Scottish ancestry; there was no known consanguinity. His father and multiple paternal relatives had hypertension; his paternal grandfather had coronary artery disease, his grandmother had an endocrine brain tumor, his aunt had Crohn’s disease, and an uncle had arthritis. His mother was healthy, his maternal grandmother had non-Hodgkin’s lymphoma, and a cousin had celiac disease. His mother, maternal grandmother, and aunt were 165 cm tall; his brother and maternal grandfather were 170 cm tall; and his father was 175 cm tall.

On examination, the blood pressure and pulse were normal. The weight was 66.3 kg (48th percentile), the height 177.5 cm (58th percentile), and the head circumference 58.5 cm (98th percentile). There was slight frontal bossing. The conjunctivae were clear, and the sclerae were white, without blue or gray hue. There was a mixed chest-wall defect, with funnel-shaped pectus excavatum and lower sternal protrusion with protrusion of parasternal cartilages (Figure 1E and 1F). A harsh, grade 3 systolic murmur was heard at the upper sternal border, without systolic click or diastolic murmur. There was loss of the normal upper curvature of the spine, as well as scoliosis, with the scapula and rib cage on the right side higher than the left. The remainder of the examination was normal or unchanged from recent previous examinations. The patient had above-average intelligence and was reserved. He asked thoughtful questions and consented to the proposed evaluations.

Figure 2.

Imaging Studies.
Dr. Sjirk J. Westra: Radiographs of the skeleton, including hands and feet, showed straightening of the normal cervical lordosis, rotatory S-shaped dextroconvex thoracic scoliosis, and generalized osteoporosis, with biconcavity of the end plates of multiple vertebral bodies, also known as “fish” or “codfish” vertebrae (Figure 2A).1,2

A dual-energy x-ray absorptiometry scan (Figure 2B) revealed an abnormally low bone mineral density of 0.75 g per square centimeter averaged over vertebral bodies L1 through L4; when compared with age-matched controls, this value resulted in a z score of _2.7, which is indicative of osteoporosis.

Dr. Lin: The blood level of phosphorus was 4.7 mg per deciliter (reference range, 3.0 to 4.5), and the level of 25-hydroxyvitamin D was 19 ng per milliliter (desired level, >32). A complete blood count and blood levels of electrolytes, folic acid, vitamin B12, calcium, glucose, total protein, albumin, and globulin were normal. Tests of renal function were also normal.

Additional diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with high myopia, craniofacial and skeletal abnormalities, and a history of speech difficulties. The patient's physical examination reveals frontal bossing, downward-slanted lateral canthi, symmetric hypoplasia of the midface and maxilla, and relative mandibular hyperplasia. The patient also has a negative overjet of more than 10 mm, and the lower teeth were retroclined. The ears were in a normal position, but they protruded outward. The patient also has a pectus excavatum present at birth. The patient's ophthalmological examination reveals microspherophakia (small, spherically shaped lenses). The patient's skeletal radiographs show straightening of the normal cervical lordosis, rotatory S-shaped dextroconvex thoracic scoliosis, and generalized osteoporosis, with biconcavity of the end plates of multiple vertebral bodies, also known as \u201cfish\u201d or \u201ccodfish\u201d vertebrae. These findings are consistent with a diagnosis of Stickler syndrome, a genetic disorder that can cause serious vision, hearing, and joint problems.\n\nDiagnosis: Stickler Syndrome""
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        ""content"": ""Weismann-Netter-Stuhl syndrome. The patient's symptoms of high myopia, craniofacial and skeletal abnormalities, including frontal bossing, downward-slanted lateral canthi, symmetric hypoplasia of the midface and maxilla, and relative mandibular hyperplasia, are all indicative of this rare condition. Additionally, the patient's dental issues, including dental crowding and class III dentofacial growth pattern, are also consistent with this diagnosis. The patient's history of speech issues and difficulty eating and chewing further support this diagnosis. The patient's skeletal abnormalities, including pectus excavatum and pectus carinatum, are also consistent with Weismann-Netter-Stuhl syndrome. Finally, the patient's ophthalmological issues, including severe myopia and microspherophakia, are also indicative of this condition.""
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        ""content"": ""The patient is a 17-year-old male presenting with high myopia, craniofacial and skeletal abnormalities, and a history of speech difficulties. The differential diagnosis for this patient includes Marfan syndrome, Ehlers-Danlos syndrome, Stickler syndrome, and Weill-Marchesani syndrome. Marfan syndrome is less likely due to the absence of cardiovascular symptoms, normal aortic-root size, and lack of joint hypermobility. Ehlers-Danlos syndrome is also less likely due to the absence of joint hypermobility and skin hyperextensibility. Stickler syndrome could present with high myopia and skeletal abnormalities, but it is often associated with hearing loss, which this patient does not have. Weill-Marchesani syndrome is characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia and high myopia, all of which are present in this patient. The patient's lack of growth after age 15 and the presence of broad thumbs also support this diagnosis. \n\nDiagnosis: Weill-Marchesani syndrome.""
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10.1056/NEJMcpc1609308,Case 33-2016 — A 30-Year-Old Woman with Severe Lower Abdominal Pain and Chill,,Tubo-ovarian abscess.,Tubo-ovarian abscess.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 30-year-old woman presented to the emergency department of this hospital with chills and sudden worsening of abdominal pain in both lower quadrants.

The patient was in her usual good health until 10 days before admission, when, after eating at a restaurant, she had nonbloody, nonbilious emesis that she attributed to food poisoning. The vomiting persisted for 2 days and then resolved. One day later, bilateral abdominal pain developed; the pain waxed and waned for a few days. She then completed a 2-day driving trip as part of her relocation to New England for a new job. During the trip, she had watery, nonbloody diarrhea every time she tried to eat (about four times per day). Her travel companion ate foods that were similar to the foods she ate but was well. After the patient arrived at her final destination, chills, fevers, and “sharp” abdominal pain in both lower quadrants, with bloating, developed. She took naproxen every 8 hours for the pain and noted some improvement. She had minimal appetite, and she noted that the frequency of the diarrheal episodes decreased when her eating decreased. However, abdominal pain persisted and intensified until she rated it as 9 to 10 on a scale of 0 to 10, with 10 indicating the most severe pain. Two nights later, she was seen in the emergency department of this hospital because of abdominal pain and distention, diarrhea, and chills.

On arrival, the patient reported nausea and increased abdominal pain without further episodes of emesis. There was no hematochezia, melena, vaginal discharge, dysuria, or foul-smelling urine. Menarche had occurred at 12 years of age. Her menstrual periods occurred in normal 30-day cycles; her most recent menstrual period had been 2 weeks before this presentation. She had had no known contact with persons who were ill. She had no chest, flank, back, or neck pain, no dyspnea, and no swelling or pain in the calves. She had not lost weight.

The patient had a history of a 1-cm ovarian cyst, which had been identified during her early teenage years. She was of East Asian descent, had lived in the Midwest for the previous 10 years, and worked in a medical field. At presentation, she was taking no medications except naproxen, as well as ibuprofen for pain during menstruation. She had no known drug allergies. She did not smoke or use alcohol or illicit drugs. She had never been sexually active. Her father had diabetes mellitus, hyperlipidemia, and hypertension. There was no family history of cancer.

On examination, the temperature was 36.5°C, the heart rate 129 beats per minute, the blood pressure 123/66 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. Her body was well developed. She appeared to be uncomfortable except when she was lying flat. She appeared to be flushed, but there was no scleral icterus or rash. She had tachycardia, but the cardiac examination was otherwise normal. The abdomen was mildly distended, with tenderness in both lower quadrants that was worst in the midline; there was voluntary guarding on palpation but no rebound, and bowel sounds were diminished. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Results of coagulation tests were normal, as were red-cell indexes and blood levels of magnesium and globulin; other test results are shown in Table 1. Two sets of blood culture specimens and a urine culture specimen were obtained. A chest radiograph showed low lung volumes and patchy bibasilar opacities. A urine test for human chorionic gonadotropin was negative.

Intravenous normal saline, ciprofloxacin, metronidazole, and morphine were administered. Imaging studies were obtained and additional diagnostic procedures were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 30-year-old woman presented to the emergency department of this hospital with chills and sudden worsening of abdominal pain in both lower quadrants.

The patient was in her usual good health until 10 days before admission, when, after eating at a restaurant, she had nonbloody, nonbilious emesis that she attributed to food poisoning. The vomiting persisted for 2 days and then resolved. One day later, bilateral abdominal pain developed; the pain waxed and waned for a few days. She then completed a 2-day driving trip as part of her relocation to New England for a new job. During the trip, she had watery, nonbloody diarrhea every time she tried to eat (about four times per day). Her travel companion ate foods that were similar to the foods she ate but was well. After the patient arrived at her final destination, chills, fevers, and “sharp” abdominal pain in both lower quadrants, with bloating, developed. She took naproxen every 8 hours for the pain and noted some improvement. She had minimal appetite, and she noted that the frequency of the diarrheal episodes decreased when her eating decreased. However, abdominal pain persisted and intensified until she rated it as 9 to 10 on a scale of 0 to 10, with 10 indicating the most severe pain. Two nights later, she was seen in the emergency department of this hospital because of abdominal pain and distention, diarrhea, and chills.

On arrival, the patient reported nausea and increased abdominal pain without further episodes of emesis. There was no hematochezia, melena, vaginal discharge, dysuria, or foul-smelling urine. Menarche had occurred at 12 years of age. Her menstrual periods occurred in normal 30-day cycles; her most recent menstrual period had been 2 weeks before this presentation. She had had no known contact with persons who were ill. She had no chest, flank, back, or neck pain, no dyspnea, and no swelling or pain in the calves. She had not lost weight.

The patient had a history of a 1-cm ovarian cyst, which had been identified during her early teenage years. She was of East Asian descent, had lived in the Midwest for the previous 10 years, and worked in a medical field. At presentation, she was taking no medications except naproxen, as well as ibuprofen for pain during menstruation. She had no known drug allergies. She did not smoke or use alcohol or illicit drugs. She had never been sexually active. Her father had diabetes mellitus, hyperlipidemia, and hypertension. There was no family history of cancer.

On examination, the temperature was 36.5°C, the heart rate 129 beats per minute, the blood pressure 123/66 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. Her body was well developed. She appeared to be uncomfortable except when she was lying flat. She appeared to be flushed, but there was no scleral icterus or rash. She had tachycardia, but the cardiac examination was otherwise normal. The abdomen was mildly distended, with tenderness in both lower quadrants that was worst in the midline; there was voluntary guarding on palpation but no rebound, and bowel sounds were diminished. The remainder of the examination was normal.

Table 1.

Laboratory Data.
Results of coagulation tests were normal, as were red-cell indexes and blood levels of magnesium and globulin; other test results are shown in Table 1. Two sets of blood culture specimens and a urine culture specimen were obtained. A chest radiograph showed low lung volumes and patchy bibasilar opacities. A urine test for human chorionic gonadotropin was negative.

Intravenous normal saline, ciprofloxacin, metronidazole, and morphine were administered. Imaging studies were obtained and additional diagnostic procedures were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of abdominal pain, bloating, and diarrhea, along with her history of an ovarian cyst, suggest a gynecological or gastrointestinal issue. The fact that her travel companion did not get sick suggests that the cause is not food poisoning. The patient's elevated white blood cell count and neutrophil percentage indicate an infection or inflammation. The patient's abdominal pain and distention, along with diminished bowel sounds, suggest a possible bowel obstruction. The patchy bibasilar opacities seen on the chest radiograph could be due to atelectasis from shallow breathing due to abdominal pain, or could indicate a lower respiratory infection. However, the patient does not report any respiratory symptoms. The negative urine test for human chorionic gonadotropin rules out pregnancy. Given these findings, the most likely diagnosis is a gastrointestinal issue, possibly appendicitis or diverticulitis. However, the patient's young age and lack of fever make diverticulitis less likely. Therefore, the most likely diagnosis is appendicitis.""
      },
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    {
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      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient's symptoms of abdominal pain, bloating, and diarrhea, along with her history of an ovarian cyst, suggest a gynecological issue. The negative test for human chorionic gonadotropin rules out pregnancy. The patient's elevated white blood cell count and neutrophil percentage indicate an infection or inflammation. The patient's elevated lactate dehydrogenase and decreased albumin levels suggest tissue damage and inflammation. The patient's elevated C-reactive protein level further supports the presence of inflammation. The patient's symptoms did not improve with antibiotics, suggesting that the cause is not bacterial. The patient's symptoms began after eating at a restaurant, but her travel companion who ate similar food did not become ill, suggesting that food poisoning is not the cause. The patient's abdominal pain is worst in the midline of her lower quadrants, which is where the uterus and ovaries are located. The patient's history of an ovarian cyst, along with her symptoms and lab results, suggest a gynecological issue such as ovarian torsion.\n\nDiagnosis: Ovarian torsion.""
      },
      ""finish_reason"": ""stop""
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}",Ovarian torsio,N,"{
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      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient is a 30-year-old woman presenting with chills, abdominal pain, bloating, and diarrhea. The differential diagnosis includes gastroenteritis, appendicitis, ovarian cyst rupture, pelvic inflammatory disease, and diverticulitis. The patient's history of a 1-cm ovarian cyst and the location of her pain could suggest an ovarian cyst rupture, but her lack of sexual activity makes pelvic inflammatory disease unlikely. Her symptoms started after eating at a restaurant, which could suggest gastroenteritis, but her travel companion who ate similar food did not fall ill. Appendicitis could also present with these symptoms, but the patient's pain is bilateral and not localized to the right lower quadrant. Diverticulitis could also present with these symptoms, but it is less common in a patient of this age. The patient's lab results show an elevated white blood cell count, which is indicative of an infection or inflammation. The patient's chest radiograph showed low lung volumes and patchy bibasilar opacities, which could suggest aspiration pneumonia, possibly due to vomiting. This could explain the patient's chills and fever. \n\nDiagnosis: Aspiration pneumonia secondary to gastroenteritis.""
      },
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}",Aspiration pneumonia secondary to gastroenteritis,N
10.1056/NEJMcpc1610098,Case 32-2016 — A 20-Year-Old Man with Gynecomastia,,Intracranial germ-cell tumor (germinoma).,A progressive lesion of the central nervous system (CNS) causing central diabetes insipidus that is progressing to masked and adipsic diabetes insipidus and is accompanied by hypopituitarism.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 20-year-old man was evaluated at this hospital because of gynecomastia.

The patient came to the hospital for a routine annual examination to establish adult care. He reported a 3-year history of bilateral breast enlargement, with no nipple discharge. He had occasional morning erections, had never been sexually active, and did not masturbate. Approximately 4 years before this evaluation, increased thirst and fluid consumption and frequent urination (four to five times during the day and up to three times each night) had developed. The patient’s parents reportedly worried that he might have diabetes, but a urinary glucose screen was negative and further evaluation was not pursued. In recent months, the frequency of urination had decreased and thirst was normal. He also reported a several-year history of blurred vision, which had been corrected with glasses; he had no diplopia and had occasional headaches after exertion. Puberty was reportedly normal. Approximately 8 months before this presentation, the frequency of shaving decreased from weekly to every 2 weeks.

Generalized nocturnal tonic–clonic seizures and focal seizures involving the right leg had occurred when the patient was between 6 and 13 years of age (approximately twice yearly, for a total of 10 to 13 generalized seizures); carbamazepine had been prescribed until the patient was 14 years of age, after which the seizures did not recur. Magnetic resonance imaging (MRI) of the head, performed at another hospital when the patient was 7 years of age, had reportedly revealed no abnormalities. His wisdom teeth had been extracted 6 months before this evaluation. He had recent constipation and a chronic pilonidal cyst. He took no medications and had no known allergies. He was a college student and lived with his parents. He drank alcohol rarely and had never smoked or used illicit drugs. His father had had a basal-cell carcinoma, a maternal uncle had had colon cancer at 36 years of age, his paternal grandfather had died of colon cancer, and his maternal grandfather had had renal cancer.

Table 1.

Laboratory Data.
On examination, the patient appeared young for his age, with minimal facial hair. The blood pressure was 98/62 mm Hg; the other vital signs were normal. The height was 179 cm, the weight 85 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 26.5. Both breasts were enlarged, with no nipple retraction, masses, or discharge. The testicles were small (approximately 2.5 cm in length). There was a small posterior anal fissure and a small lump over the coccyx with a central punctum and no discharge; the remainder of the examination was normal. The stool was negative for occult blood. The hematocrit, hemoglobin level, platelet count, and white-cell count were normal; the white cells consisted of 37.3% neutrophils (reference range, 40 to 62), 49.3% lymphocytes (reference range, 27 to 40), and normal percentages of monocytes, eosinophils, and basophils. Blood levels of total protein, albumin, globulin, total bilirubin, alkaline phosphatase, and alanine aminotransferase were normal; other test results are shown in Table 1. During the next 3 days, additional laboratory test results were obtained (Table 1). Urinalysis was normal; the specific gravity was 1.008 (reference range, 1.001 to 1.035).

Additional diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 20-year-old man was evaluated at this hospital because of gynecomastia.

The patient came to the hospital for a routine annual examination to establish adult care. He reported a 3-year history of bilateral breast enlargement, with no nipple discharge. He had occasional morning erections, had never been sexually active, and did not masturbate. Approximately 4 years before this evaluation, increased thirst and fluid consumption and frequent urination (four to five times during the day and up to three times each night) had developed. The patient’s parents reportedly worried that he might have diabetes, but a urinary glucose screen was negative and further evaluation was not pursued. In recent months, the frequency of urination had decreased and thirst was normal. He also reported a several-year history of blurred vision, which had been corrected with glasses; he had no diplopia and had occasional headaches after exertion. Puberty was reportedly normal. Approximately 8 months before this presentation, the frequency of shaving decreased from weekly to every 2 weeks.

Generalized nocturnal tonic–clonic seizures and focal seizures involving the right leg had occurred when the patient was between 6 and 13 years of age (approximately twice yearly, for a total of 10 to 13 generalized seizures); carbamazepine had been prescribed until the patient was 14 years of age, after which the seizures did not recur. Magnetic resonance imaging (MRI) of the head, performed at another hospital when the patient was 7 years of age, had reportedly revealed no abnormalities. His wisdom teeth had been extracted 6 months before this evaluation. He had recent constipation and a chronic pilonidal cyst. He took no medications and had no known allergies. He was a college student and lived with his parents. He drank alcohol rarely and had never smoked or used illicit drugs. His father had had a basal-cell carcinoma, a maternal uncle had had colon cancer at 36 years of age, his paternal grandfather had died of colon cancer, and his maternal grandfather had had renal cancer.

Table 1.

Laboratory Data.
On examination, the patient appeared young for his age, with minimal facial hair. The blood pressure was 98/62 mm Hg; the other vital signs were normal. The height was 179 cm, the weight 85 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 26.5. Both breasts were enlarged, with no nipple retraction, masses, or discharge. The testicles were small (approximately 2.5 cm in length). There was a small posterior anal fissure and a small lump over the coccyx with a central punctum and no discharge; the remainder of the examination was normal. The stool was negative for occult blood. The hematocrit, hemoglobin level, platelet count, and white-cell count were normal; the white cells consisted of 37.3% neutrophils (reference range, 40 to 62), 49.3% lymphocytes (reference range, 27 to 40), and normal percentages of monocytes, eosinophils, and basophils. Blood levels of total protein, albumin, globulin, total bilirubin, alkaline phosphatase, and alanine aminotransferase were normal; other test results are shown in Table 1. During the next 3 days, additional laboratory test results were obtained (Table 1). Urinalysis was normal; the specific gravity was 1.008 (reference range, 1.001 to 1.035).

Additional diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with gynecomastia, decreased frequency of shaving, small testicles, and a history of seizures. These symptoms suggest a hormonal imbalance, possibly due to a pituitary issue. The patient also reports a history of increased thirst and urination, which could indicate diabetes insipidus, another condition that can be caused by pituitary dysfunction. The patient's blurred vision could be due to a pituitary tumor pressing on the optic nerve. The patient's lab results show low testosterone and high prolactin, which further supports a pituitary issue. The patient's low specific gravity in his urine also supports the diagnosis of diabetes insipidus. \n\nDiagnosis: Pituitary adenoma causing hypogonadism and diabetes insipidus.""
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        ""content"": ""The patient has a history of gynecomastia, decreased frequency of shaving, small testicles, and a history of seizures. These symptoms suggest a hormonal imbalance, possibly due to a pituitary issue. The patient also has a history of increased thirst and urination, which could be a symptom of diabetes insipidus, a condition often caused by problems with the pituitary gland. The patient's blurred vision could be due to a pituitary tumor pressing on the optic nerve. The patient's lab results show low testosterone and high prolactin, which are also indicative of a pituitary issue. \n\nDiagnosis: \nPituitary adenoma""
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        ""content"": ""This is a 20-year-old male who presents with a 3-year history of bilateral gynecomastia, decreased frequency of shaving, small testicles, and a history of seizures. He also reports a history of polyuria and polydipsia, which have since resolved, and blurred vision. The differential diagnosis for this patient includes Klinefelter syndrome, hypogonadism, hyperprolactinemia, and a pituitary tumor. Klinefelter syndrome is a genetic condition that results in small testicles, gynecomastia, and decreased facial hair, but it does not typically cause seizures, polyuria, or polydipsia. Hypogonadism can cause gynecomastia and small testicles, but it also does not typically cause seizures, polyuria, or polydipsia. Hyperprolactinemia can cause gynecomastia and decreased facial hair, but it does not typically cause small testicles, seizures, polyuria, or polydipsia. A pituitary tumor, however, can cause all of these symptoms. A pituitary tumor can cause gynecomastia and decreased facial hair by disrupting the normal hormonal balance. It can cause small testicles by decreasing the production of luteinizing hormone and follicle-stimulating hormone. It can cause seizures by growing large enough to compress the surrounding brain tissue. It can cause polyuria and polydipsia by disrupting the production of antidiuretic hormone, leading to diabetes insipidus. It can cause blurred vision by compressing the optic chiasm. Given the patient's constellation of symptoms, a pituitary tumor is the most likely diagnosis.\n\nDiagnosis: Pituitary tumor.""
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}",Pituitary tumor,Y
10.1056/NEJMcpc1610097,"Case 31-2016 — A 53-Year-Old Man with Diplopia, Polydipsia, and Polyuria",,IgG4-related hypophysitis.,IgG4-related hypophysitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 53-year-old man was seen in the neurology, neurosurgery, and neuroendocrinology clinics of this hospital because of diplopia, polydipsia, and polyuria.

The patient had been well until approximately 1 year before this evaluation, when nasal congestion and headache developed. During the next 3 months, his symptoms worsened.

Figure 1.

MRI Scans Obtained over a 9-Month Period.
Dr. Otto Rapalino: Nine months before this evaluation, magnetic resonance imaging (MRI) of the head without the administration of contrast material was performed at another hospital (Figure 1A). The imaging studies revealed diffuse mucosal thickening of the right sphenoid sinus, with inspissated secretions filling that sinus, and scattered mild mucosal thickening within the left sphenoid, ethmoid, and maxillary sinuses.

Dr. Byrne: The patient was treated with a course of antibiotics, but there was no improvement. One month later, endoscopic sinus surgery with maxillary antrostomy and septoplasty was performed at a second hospital.

Two weeks after surgery (approximately 7.5 months before this evaluation), diplopia developed that worsened on lateral gaze; there was no ocular pain, proptosis, facial numbness, or swelling. On examination by a neuro-ophthalmologist, mild deficits on abduction that involved both eyes, with the right deficit more severe than the left, and a large-angle esotropia were noted. A diagnosis of a right sixth-nerve palsy was made.

Dr. Rapalino: Seven months before this evaluation, MRI of the head with the administration of gadolinium was performed (Figure 1B). The imaging studies revealed changes consistent with persistent inflammation of the sphenoid sinuses and diffuse enlargement of the pituitary gland, which measured 17 mm in the maximal transverse dimension and 9 mm in the maximal craniocaudal dimension.

Dr. Byrne: Methylprednisolone and antibiotics were administered for 3 weeks, and the diplopia resolved 6 weeks after onset. Mild to moderately severe headaches, worse in the evenings, persisted.

Approximately 4.5 months before this evaluation, polydipsia and polyuria developed. Urine volume measured up to 6 liters daily, and the specific gravity was less than 1.005. The level of plasma antidiuretic hormone was reportedly undetectable during a water-deprivation test. The urine osmolality did not increase in response to water deprivation but increased by 150% after the administration of desmopressin. Treatment with nasally administered desmopressin was begun and resulted in a decrease in urinary frequency, nocturia, and thirst.

Dr. Rapalino: Three months before this evaluation, repeat MRI of the head, performed with the administration of gadolinium (Figure 1C), revealed extensive mucosal thickening and partial filling of the right sphenoid sinus with secretions, with enlargement of the pituitary gland to 19 mm by 11 mm by 13 mm (maximal transverse, craniocaudal, and anteroposterior dimensions, respectively), as compared with 16 mm by 7 mm by 11 mm 7 months earlier and 17 mm by 9 mm by 12 mm 5 months earlier. The pituitary gland showed homogeneous enhancement after gadolinium administration and had an abnormal superior convexity. The infundibular stalk also appeared to be mildly thickened.

Table 1.

Laboratory Data.
Dr. Byrne: Eight days after the repeat MRI was performed, diplopia recurred. Approximately 6 weeks before this evaluation, neuro-ophthalmologic examination revealed minor bilateral abduction deficits. Laboratory test results are shown in Table 1. Analysis of cerebrospinal fluid (CSF) showed 4 white cells per cubic millimeter (97% lymphocytes and 3% monocytes), a protein level of 66 mg per deciliter (reference range, 15 to 45), and normal levels of glucose, alpha-fetoprotein, and angiotensin-converting enzyme. The test for human chorionic gonadotropin was negative. The patient was prescribed a 3-week course of levofloxacin and referred to this hospital.

On evaluation at this hospital, the patient reported nocturia and mild headache; his diplopia had resolved within the previous month. He had been physically active and had run 12 miles weekly until 3 months before this evaluation, when leg fatigue developed. He shaved daily and reported a weight gain of 3 to 4 kg (6 to 8 lb), mild muscle soreness, and extreme sensitivity to cold. His shoe size had increased by half a size over a period of several years. He had no unexplained sweating, arthralgias, nausea, constipation, dizziness, faintness, breast tenderness, edema, bruising, rash, erectile dysfunction, low libido, or history of colon polyps. He had had hepatitis A virus infection and had undergone knee arthroscopy in the remote past. He had undergone herniorrhaphy as an infant. Medications included desmopressin nasal spray (administered twice daily), levofloxacin, and, as needed, ibuprofen, acetaminophen, and diphenhydramine. He had no known allergies. He was married, lived in a midwestern state, and worked in sales. He did not drink alcohol, smoke tobacco, or use illicit drugs. His father had died from amyotrophic lateral sclerosis, and his mother from lung cancer; his mother had also had hypothyroidism.

On examination, the vital signs were normal, as was the otolaryngologic examination. The frontal and maxillary sinuses were not tender, and nasal endoscopy revealed normal mucosa; there was no evidence of mucopurulent discharge, and the lacrimal and salivary glands were normal. There was no proptosis or ocular inflammation. The remainder of the general and neurologic examination, including examination of the cranial nerves, was normal. The white-cell count, white-cell differential count, and platelet count were normal, as were blood levels of electrolytes, albumin, globulin, total protein, glucose, calculated mean blood glucose, glycated hemoglobin, calcium, and prostate-specific antigen. Results of liver-function and renal-function tests were normal, as was the urinalysis; other test results are shown in Table 1. An electrocardiogram and a chest radiograph were normal.

Figure 2.

Pretreatment and Post-Treatment Imaging Studies.
Dr. Rapalino: MRI of the pituitary, performed both without and with the administration of gadolinium (Figure 1D and Figure 2B and 2E), revealed diffuse enlargement of the pituitary gland and the infundibular stalk, preservation of the sellar floor, and extensive mucosal thickening in the sphenoid sinus. On T2-weighted images, circumferential hypointense and enhancing soft tissue was again noted, partially filling the right sphenoid sinus; the size of the soft tissue was larger than its size on the first MRI but was stable when compared with the finding on the imaging study performed 7 months earlier. Computed tomography (CT) of the face and sinuses showed expansion of the pituitary fossa and thickening and sclerosis of the adjacent sphenoid sinus walls, findings that suggested chronic inflammatory changes (Figure 2A and 2D).

Dr. Byrne: A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 53-year-old man was seen in the neurology, neurosurgery, and neuroendocrinology clinics of this hospital because of diplopia, polydipsia, and polyuria.

The patient had been well until approximately 1 year before this evaluation, when nasal congestion and headache developed. During the next 3 months, his symptoms worsened.

Figure 1.

MRI Scans Obtained over a 9-Month Period.
Dr. Otto Rapalino: Nine months before this evaluation, magnetic resonance imaging (MRI) of the head without the administration of contrast material was performed at another hospital (Figure 1A). The imaging studies revealed diffuse mucosal thickening of the right sphenoid sinus, with inspissated secretions filling that sinus, and scattered mild mucosal thickening within the left sphenoid, ethmoid, and maxillary sinuses.

Dr. Byrne: The patient was treated with a course of antibiotics, but there was no improvement. One month later, endoscopic sinus surgery with maxillary antrostomy and septoplasty was performed at a second hospital.

Two weeks after surgery (approximately 7.5 months before this evaluation), diplopia developed that worsened on lateral gaze; there was no ocular pain, proptosis, facial numbness, or swelling. On examination by a neuro-ophthalmologist, mild deficits on abduction that involved both eyes, with the right deficit more severe than the left, and a large-angle esotropia were noted. A diagnosis of a right sixth-nerve palsy was made.

Dr. Rapalino: Seven months before this evaluation, MRI of the head with the administration of gadolinium was performed (Figure 1B). The imaging studies revealed changes consistent with persistent inflammation of the sphenoid sinuses and diffuse enlargement of the pituitary gland, which measured 17 mm in the maximal transverse dimension and 9 mm in the maximal craniocaudal dimension.

Dr. Byrne: Methylprednisolone and antibiotics were administered for 3 weeks, and the diplopia resolved 6 weeks after onset. Mild to moderately severe headaches, worse in the evenings, persisted.

Approximately 4.5 months before this evaluation, polydipsia and polyuria developed. Urine volume measured up to 6 liters daily, and the specific gravity was less than 1.005. The level of plasma antidiuretic hormone was reportedly undetectable during a water-deprivation test. The urine osmolality did not increase in response to water deprivation but increased by 150% after the administration of desmopressin. Treatment with nasally administered desmopressin was begun and resulted in a decrease in urinary frequency, nocturia, and thirst.

Dr. Rapalino: Three months before this evaluation, repeat MRI of the head, performed with the administration of gadolinium (Figure 1C), revealed extensive mucosal thickening and partial filling of the right sphenoid sinus with secretions, with enlargement of the pituitary gland to 19 mm by 11 mm by 13 mm (maximal transverse, craniocaudal, and anteroposterior dimensions, respectively), as compared with 16 mm by 7 mm by 11 mm 7 months earlier and 17 mm by 9 mm by 12 mm 5 months earlier. The pituitary gland showed homogeneous enhancement after gadolinium administration and had an abnormal superior convexity. The infundibular stalk also appeared to be mildly thickened.

Table 1.

Laboratory Data.
Dr. Byrne: Eight days after the repeat MRI was performed, diplopia recurred. Approximately 6 weeks before this evaluation, neuro-ophthalmologic examination revealed minor bilateral abduction deficits. Laboratory test results are shown in Table 1. Analysis of cerebrospinal fluid (CSF) showed 4 white cells per cubic millimeter (97% lymphocytes and 3% monocytes), a protein level of 66 mg per deciliter (reference range, 15 to 45), and normal levels of glucose, alpha-fetoprotein, and angiotensin-converting enzyme. The test for human chorionic gonadotropin was negative. The patient was prescribed a 3-week course of levofloxacin and referred to this hospital.

On evaluation at this hospital, the patient reported nocturia and mild headache; his diplopia had resolved within the previous month. He had been physically active and had run 12 miles weekly until 3 months before this evaluation, when leg fatigue developed. He shaved daily and reported a weight gain of 3 to 4 kg (6 to 8 lb), mild muscle soreness, and extreme sensitivity to cold. His shoe size had increased by half a size over a period of several years. He had no unexplained sweating, arthralgias, nausea, constipation, dizziness, faintness, breast tenderness, edema, bruising, rash, erectile dysfunction, low libido, or history of colon polyps. He had had hepatitis A virus infection and had undergone knee arthroscopy in the remote past. He had undergone herniorrhaphy as an infant. Medications included desmopressin nasal spray (administered twice daily), levofloxacin, and, as needed, ibuprofen, acetaminophen, and diphenhydramine. He had no known allergies. He was married, lived in a midwestern state, and worked in sales. He did not drink alcohol, smoke tobacco, or use illicit drugs. His father had died from amyotrophic lateral sclerosis, and his mother from lung cancer; his mother had also had hypothyroidism.

On examination, the vital signs were normal, as was the otolaryngologic examination. The frontal and maxillary sinuses were not tender, and nasal endoscopy revealed normal mucosa; there was no evidence of mucopurulent discharge, and the lacrimal and salivary glands were normal. There was no proptosis or ocular inflammation. The remainder of the general and neurologic examination, including examination of the cranial nerves, was normal. The white-cell count, white-cell differential count, and platelet count were normal, as were blood levels of electrolytes, albumin, globulin, total protein, glucose, calculated mean blood glucose, glycated hemoglobin, calcium, and prostate-specific antigen. Results of liver-function and renal-function tests were normal, as was the urinalysis; other test results are shown in Table 1. An electrocardiogram and a chest radiograph were normal.

Figure 2.

Pretreatment and Post-Treatment Imaging Studies.
Dr. Rapalino: MRI of the pituitary, performed both without and with the administration of gadolinium (Figure 1D and Figure 2B and 2E), revealed diffuse enlargement of the pituitary gland and the infundibular stalk, preservation of the sellar floor, and extensive mucosal thickening in the sphenoid sinus. On T2-weighted images, circumferential hypointense and enhancing soft tissue was again noted, partially filling the right sphenoid sinus; the size of the soft tissue was larger than its size on the first MRI but was stable when compared with the finding on the imaging study performed 7 months earlier. Computed tomography (CT) of the face and sinuses showed expansion of the pituitary fossa and thickening and sclerosis of the adjacent sphenoid sinus walls, findings that suggested chronic inflammatory changes (Figure 2A and 2D).

Dr. Byrne: A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 53-year-old man presenting with diplopia, polydipsia, and polyuria. He also has a history of nasal congestion and headache. The differential diagnosis for this patient includes diabetes insipidus, pituitary adenoma, and sinusitis. The patient's symptoms of polydipsia and polyuria, along with a low specific gravity and undetectable levels of plasma antidiuretic hormone during a water-deprivation test, are indicative of diabetes insipidus. However, the patient also has diplopia and a history of nasal congestion and headache, which are not typically associated with diabetes insipidus. The MRI findings of diffuse enlargement of the pituitary gland and the infundibular stalk, along with the patient's symptoms of diplopia, suggest a pituitary adenoma. However, the patient does not have other common symptoms of a pituitary adenoma, such as changes in vision, unexplained weight gain or loss, or changes in menstrual cycles for women. The patient's history of nasal congestion and headache, along with the MRI findings of mucosal thickening in the sphenoid sinus, suggest sinusitis. However, the patient's symptoms of polydipsia and polyuria are not typically associated with sinusitis. Given the combination of the patient's symptoms and the MRI findings, the most likely diagnosis is a pituitary adenoma causing secondary diabetes insipidus.\n\nDiagnosis: Pituitary adenoma causing secondary diabetes insipidus.""
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}",Pituitary adenoma causing secondary diabetes insipidu,N
10.1056/NEJMcpc1609309,"Case 30-2016 — A 63-Year-Old Woman with Bipolar Disorder, Cancer, and Worsening Depression",,Bipolar I disorder with mixed features; invasive ductal carcinoma of the breast; lung cancer.,"Bipolar I disorder, with a current episode of depression of moderate severity and with mixed features; attention deficit–hyperactivity disorder (as determined by the patient’s history); nonadherence to prescribed medical treatments; tobacco use disorder; history of lung cancer; and early-stage breast cancer.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 63-year-old woman with bipolar disorder, worsening depression, and multiple other medical conditions, including lung cancer and breast cancer, was admitted to the inpatient psychiatry service of this hospital for electroconvulsive therapy (ECT).

The patient had a long-standing history of bipolar disorder, including depressive episodes, which were characterized by low motivation, low energy, a feeling of hopelessness, agoraphobia, and suicidal ideation without suicide attempts, and brief episodes, each lasting for 2 to 3 weeks, of hypomania and mania with irritable or elevated mood, labile affect, pressured speech, and a decreased need for sleep. Twelve years before this admission, she had received a diagnosis of stage IIA estrogen-receptor–positive and progesterone-receptor–positive, HER2/neu-negative invasive ductal carcinoma of the left breast, with lymphatic-vessel invasion and isolated tumor cells in 2 of 2 lymph nodes. The patient underwent lumpectomy and adjuvant whole-breast radiation therapy. Follow-up therapy included four cycles of doxorubicin and cyclophosphamide chemotherapy and a 5-year course of tamoxifen. She had also been hospitalized three times for mania with psychotic features, including paranoia and visual hallucinations; her most recent hospitalization for mania occurred during her treatment for breast cancer, 11 years before this admission for ECT. She also had attention deficit–hyperactivity disorder (ADHD). Over the years, she had been treated with lithium, stimulants, atypical antipsychotic agents, and multiple classes of antidepressants.

Six years before this admission, the patient discontinued primary care follow-up, and shortly thereafter she discontinued psychiatric care. Two years before this admission, a diagnosis of stage II non–small-cell carcinoma of the right lung was made. At the time of the diagnosis, she was referred to a psychiatrist at the cancer center of this hospital. Her medications were adjusted, and her depression abated. She underwent a right upper lobectomy and received adjuvant chemotherapy.

Approximately 1 year before this admission, the patient’s depression and anxiety worsened. She missed multiple medical and psychiatric appointments, but she communicated with some practitioners by telephone. She agreed to undergo ECT for refractory depression and was admitted to this hospital.

On admission, the patient reported sad mood, low interest, low energy, a feeling of hopelessness, and fear of leaving her home and burdening her husband. She had no hallucinations or thoughts of harming herself or others. She had asthma, chronic obstructive pulmonary disease, hypertension, hypercholesterolemia, insomnia, and the restless leg syndrome. A hip fracture had been repaired. Medications on admission included bupropion, gabapentin, modafinil, quetiapine, and sertraline, as well as inhaled albuterol, ipratropium, budesonide, and tiotropium. She was allergic to pramipexole and lithium carbonate, which caused myoclonic movements. She was married and retired, received disability assistance, and lived with her husband, who also had mental illness. Her mother had had depression and had died from myocardial infarction when she was in her 50s, her father had died from leukemia in his 50s, and her paternal grandfather had died from stomach cancer in his 60s. There was no family history of breast cancer or lung cancer. The patient smoked one to two packs of cigarettes daily and did not currently drink alcohol; she had used cannabis, cocaine, and hallucinogens in the distant past and had never used intravenous drugs.

On examination, the blood pressure was 140/73 mm Hg, and the pulse 101 beats per minute. The temperature and respiratory rate were normal. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 27.2. The patient’s appearance was disheveled, her hygiene was fair, and she was alert and understood the reason for her hospitalization. She was easily distracted but cooperative. Her speech was rapid and occasionally loud but interruptible; she was mildly restless. Her mood was “sad” and her affect alternated between dysphoric and mildly expansive. Her thought process was occasionally tangential but redirectable. There was no evidence of delusion or paranoia, and she did not appear to respond to internal stimuli. She had insight into her worsening depression and agreed to undergo ECT. The physical examination revealed diffuse inspiratory and expiratory wheezes.

The blood urea nitrogen level was 26 mg per deciliter (9.3 mmol per liter; reference range, 8 to 25 mg per deciliter [2.9 to 8.9 mmol per liter]), the creatinine level was 1.31 mg per deciliter (116 _mol per liter; reference range, 0.60 to 1.50 mg per deciliter [53.0 to 133 _mol per liter]), and the estimated glomerular filtration rate was 41 ml per minute per 1.73 m2 of body-surface area (reference value, ≥60). The complete blood count and blood levels of electrolytes, vitamin B12, folic acid, calcium, phosphorus, magnesium, glucose, total protein, albumin, globulin, and thyrotropin were normal, as were results of liver-function tests. Screening tests for syphilis and human immunodeficiency virus antibodies and p24 antigen were nonreactive. An electrocardiogram was normal.

Figure 1.

Imaging Studies.
Dr. Phoebe E. Freer: Computed tomography (CT) of the chest was performed to assess the status of the patient’s known, treated lung cancer. Changes attributed to a lobectomy of the right lower lobe and a segmentectomy of the posterior right upper lobe for a lung cancer were noted, with no new findings or findings that were suspicious for recurrent lung cancer. However, a rim-enhancing mass was noted at the 11 o’clock position in the right breast; this mass was new since the previous chest CT scan obtained 16 months earlier (Figure 1A). Mammography and ultrasonography were recommended as follow-up diagnostic procedures. Magnetic resonance imaging (MRI) of the head, performed the day after the chest CT, revealed no evidence of an intracranial mass, hemorrhage, or acute infarction.

Dr. Daunis: The patient received six ECT treatments during her hospitalization. These treatments resulted in moderate improvement in her mood. She was discharged on the 19th hospital day. Medications on discharge were gabapentin (1200 mg at bedtime), lamotrigine (50 mg daily), modafinil (400 mg daily), and quetiapine (600 mg at bedtime), and tiotropium, ipratropium, and albuterol sulfate inhalers.

Dr. Freer: After the patient was discharged from the hospital, mammography, performed on an outpatient basis, revealed an irregularly shaped mass in the right breast (Figure 1B and 1C), with spiculated margins and associated architectural distortion. This finding correlated with that of the chest CT scan and was a new finding since the patient’s most recent mammogram 2 years earlier (Figure 1D and 1E). Ultrasonography of the right breast, targeted at the 11 o’clock position, confirmed the presence of a solid mass, measuring 14 mm in the maximal dimension, that was highly suspicious for primary breast cancer. A core biopsy was recommended.

Figure 2.

Breast-Biopsy Specimens.
Dr. Thomas M. Gudewicz: Cytopathological specimens of breast tissue obtained by means of ultrasound-guided fine-needle aspiration contained individual moderately enlarged atypical epithelial cells, as well as clusters of such cells. These cells had a high nuclear-to-cytoplasmic ratio, irregular nuclear contours, fine chromatin, and occasional small nucleoli (Figure 2A). Mitotic figures were occasionally identifiable. The carcinoma cells were compatible with a primary breast cancer, but they could also have arisen from a metastasis of the lung carcinoma. In addition, other primary carcinomas can metastasize to the breast, including lung, bronchial, endometrial, colon, and thyroid cancers and melanoma.

We attempted to distinguish the two tumors through immunohistochemical analysis using a select immunoprofile with thyroid transcription factor 1 (TTF1) and mammaglobin. The TTF1 immunostain is positive in nearly all pulmonary carcinomas and is only rarely positive in breast cancers. Mammaglobin is negative in pulmonary tumors and is generally positive in breast cancers. An attempt was made to stain a cell-block preparation with these two immunostains, but the sample was paucicellular, and the staining was inconclusive. Comparison of the morphologic characteristics of the breast tumor with those of the previous lung tumor showed that cells obtained from the lung tumor had a higher nuclear grade than those obtained from the breast specimen (Figure 2B). A primary breast tumor was therefore considered to be the likely diagnosis.

Dr. Daunis: Lumpectomy with a sentinel-lymph-node biopsy was recommended, but the patient reported worsening depression, and she did not keep her follow-up appointments. Management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 63-year-old woman with bipolar disorder, worsening depression, and multiple other medical conditions, including lung cancer and breast cancer, was admitted to the inpatient psychiatry service of this hospital for electroconvulsive therapy (ECT).

The patient had a long-standing history of bipolar disorder, including depressive episodes, which were characterized by low motivation, low energy, a feeling of hopelessness, agoraphobia, and suicidal ideation without suicide attempts, and brief episodes, each lasting for 2 to 3 weeks, of hypomania and mania with irritable or elevated mood, labile affect, pressured speech, and a decreased need for sleep. Twelve years before this admission, she had received a diagnosis of stage IIA estrogen-receptor–positive and progesterone-receptor–positive, HER2/neu-negative invasive ductal carcinoma of the left breast, with lymphatic-vessel invasion and isolated tumor cells in 2 of 2 lymph nodes. The patient underwent lumpectomy and adjuvant whole-breast radiation therapy. Follow-up therapy included four cycles of doxorubicin and cyclophosphamide chemotherapy and a 5-year course of tamoxifen. She had also been hospitalized three times for mania with psychotic features, including paranoia and visual hallucinations; her most recent hospitalization for mania occurred during her treatment for breast cancer, 11 years before this admission for ECT. She also had attention deficit–hyperactivity disorder (ADHD). Over the years, she had been treated with lithium, stimulants, atypical antipsychotic agents, and multiple classes of antidepressants.

Six years before this admission, the patient discontinued primary care follow-up, and shortly thereafter she discontinued psychiatric care. Two years before this admission, a diagnosis of stage II non–small-cell carcinoma of the right lung was made. At the time of the diagnosis, she was referred to a psychiatrist at the cancer center of this hospital. Her medications were adjusted, and her depression abated. She underwent a right upper lobectomy and received adjuvant chemotherapy.

Approximately 1 year before this admission, the patient’s depression and anxiety worsened. She missed multiple medical and psychiatric appointments, but she communicated with some practitioners by telephone. She agreed to undergo ECT for refractory depression and was admitted to this hospital.

On admission, the patient reported sad mood, low interest, low energy, a feeling of hopelessness, and fear of leaving her home and burdening her husband. She had no hallucinations or thoughts of harming herself or others. She had asthma, chronic obstructive pulmonary disease, hypertension, hypercholesterolemia, insomnia, and the restless leg syndrome. A hip fracture had been repaired. Medications on admission included bupropion, gabapentin, modafinil, quetiapine, and sertraline, as well as inhaled albuterol, ipratropium, budesonide, and tiotropium. She was allergic to pramipexole and lithium carbonate, which caused myoclonic movements. She was married and retired, received disability assistance, and lived with her husband, who also had mental illness. Her mother had had depression and had died from myocardial infarction when she was in her 50s, her father had died from leukemia in his 50s, and her paternal grandfather had died from stomach cancer in his 60s. There was no family history of breast cancer or lung cancer. The patient smoked one to two packs of cigarettes daily and did not currently drink alcohol; she had used cannabis, cocaine, and hallucinogens in the distant past and had never used intravenous drugs.

On examination, the blood pressure was 140/73 mm Hg, and the pulse 101 beats per minute. The temperature and respiratory rate were normal. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 27.2. The patient’s appearance was disheveled, her hygiene was fair, and she was alert and understood the reason for her hospitalization. She was easily distracted but cooperative. Her speech was rapid and occasionally loud but interruptible; she was mildly restless. Her mood was “sad” and her affect alternated between dysphoric and mildly expansive. Her thought process was occasionally tangential but redirectable. There was no evidence of delusion or paranoia, and she did not appear to respond to internal stimuli. She had insight into her worsening depression and agreed to undergo ECT. The physical examination revealed diffuse inspiratory and expiratory wheezes.

The blood urea nitrogen level was 26 mg per deciliter (9.3 mmol per liter; reference range, 8 to 25 mg per deciliter [2.9 to 8.9 mmol per liter]), the creatinine level was 1.31 mg per deciliter (116 _mol per liter; reference range, 0.60 to 1.50 mg per deciliter [53.0 to 133 _mol per liter]), and the estimated glomerular filtration rate was 41 ml per minute per 1.73 m2 of body-surface area (reference value, ≥60). The complete blood count and blood levels of electrolytes, vitamin B12, folic acid, calcium, phosphorus, magnesium, glucose, total protein, albumin, globulin, and thyrotropin were normal, as were results of liver-function tests. Screening tests for syphilis and human immunodeficiency virus antibodies and p24 antigen were nonreactive. An electrocardiogram was normal.

Figure 1.

Imaging Studies.
Dr. Phoebe E. Freer: Computed tomography (CT) of the chest was performed to assess the status of the patient’s known, treated lung cancer. Changes attributed to a lobectomy of the right lower lobe and a segmentectomy of the posterior right upper lobe for a lung cancer were noted, with no new findings or findings that were suspicious for recurrent lung cancer. However, a rim-enhancing mass was noted at the 11 o’clock position in the right breast; this mass was new since the previous chest CT scan obtained 16 months earlier (Figure 1A). Mammography and ultrasonography were recommended as follow-up diagnostic procedures. Magnetic resonance imaging (MRI) of the head, performed the day after the chest CT, revealed no evidence of an intracranial mass, hemorrhage, or acute infarction.

Dr. Daunis: The patient received six ECT treatments during her hospitalization. These treatments resulted in moderate improvement in her mood. She was discharged on the 19th hospital day. Medications on discharge were gabapentin (1200 mg at bedtime), lamotrigine (50 mg daily), modafinil (400 mg daily), and quetiapine (600 mg at bedtime), and tiotropium, ipratropium, and albuterol sulfate inhalers.

Dr. Freer: After the patient was discharged from the hospital, mammography, performed on an outpatient basis, revealed an irregularly shaped mass in the right breast (Figure 1B and 1C), with spiculated margins and associated architectural distortion. This finding correlated with that of the chest CT scan and was a new finding since the patient’s most recent mammogram 2 years earlier (Figure 1D and 1E). Ultrasonography of the right breast, targeted at the 11 o’clock position, confirmed the presence of a solid mass, measuring 14 mm in the maximal dimension, that was highly suspicious for primary breast cancer. A core biopsy was recommended.

Figure 2.

Breast-Biopsy Specimens.
Dr. Thomas M. Gudewicz: Cytopathological specimens of breast tissue obtained by means of ultrasound-guided fine-needle aspiration contained individual moderately enlarged atypical epithelial cells, as well as clusters of such cells. These cells had a high nuclear-to-cytoplasmic ratio, irregular nuclear contours, fine chromatin, and occasional small nucleoli (Figure 2A). Mitotic figures were occasionally identifiable. The carcinoma cells were compatible with a primary breast cancer, but they could also have arisen from a metastasis of the lung carcinoma. In addition, other primary carcinomas can metastasize to the breast, including lung, bronchial, endometrial, colon, and thyroid cancers and melanoma.

We attempted to distinguish the two tumors through immunohistochemical analysis using a select immunoprofile with thyroid transcription factor 1 (TTF1) and mammaglobin. The TTF1 immunostain is positive in nearly all pulmonary carcinomas and is only rarely positive in breast cancers. Mammaglobin is negative in pulmonary tumors and is generally positive in breast cancers. An attempt was made to stain a cell-block preparation with these two immunostains, but the sample was paucicellular, and the staining was inconclusive. Comparison of the morphologic characteristics of the breast tumor with those of the previous lung tumor showed that cells obtained from the lung tumor had a higher nuclear grade than those obtained from the breast specimen (Figure 2B). A primary breast tumor was therefore considered to be the likely diagnosis.

Dr. Daunis: Lumpectomy with a sentinel-lymph-node biopsy was recommended, but the patient reported worsening depression, and she did not keep her follow-up appointments. Management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Recurrent Breast Cancer. The patient has a history of breast cancer and a new mass was found in her right breast. The biopsy of the mass showed atypical epithelial cells, which are indicative of cancer. The cells from the new mass were compared to cells from her previous lung tumor and were found to have a higher nuclear grade, suggesting that the new mass is a primary breast tumor rather than a metastasis from the lung.""
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10.1056/NEJMcpc1609109,Bipolar I disorder with mixed features; invasive ductal carcinoma of the breast; lung cancer.,,Histoplasmosis of the breast.,Breast Cancer,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 53-year-old woman with systemic lupus erythematosus with associated nephritis and chronic renal insufficiency was seen in the gynecology clinic of this hospital because of pain and a lump in the left breast.

Table 1.

Laboratory Data.
The patient had been in her usual health until 4 months before this presentation, when she noted a small, tender lump in the left breast on self-examination. Evaluation by her primary care physician revealed a firm, slightly mobile mass (measuring 5 mm in greatest dimension) in the upper inner quadrant of the left breast. The skin overlying the mass appeared normal, and there was no nipple discharge or axillary lymphadenopathy. The right breast and the remainder of the physical examination were normal. Three days earlier, routine laboratory tests had been performed by her nephrologist; the test results are shown in Table 1.

Figure 1.

Imaging Studies of the Left Breast, Obtained at the Time of the Initial Presentation.
Dr. Pragya A. Dang: Three days later, combined digital mammography and tomosynthesis of the left breast was negative, with no suspicious masses, areas of architectural distortion, or microcalcifications (Figure 1). Ultrasonography targeted to the 10 o’clock position in the left breast revealed a superficial, hyperechoic, oval mass (measuring 6 mm in greatest dimension) with circumscribed margins that was located 5 cm from the nipple, in the dermis. The radiologic differential diagnosis included a sebaceous cyst, and the mass was thought to be probably benign. A plan was made to perform follow-up imaging in 6 months.

Dr. Letourneau: Two months later, the patient was seen for routine follow-up in the nephrology and rheumatology clinics of this hospital. She reported fatigue, nausea, and epigastric pain. Mild epigastric tenderness was present; the remainder of the physical examination was normal. Laboratory test results are shown in Table 1. One month later, computed tomography of the abdomen and pelvis, performed without the administration of contrast material, revealed no evidence of pancreatitis; there was a new, indeterminate, hyperdense lesion (measuring 1.9 cm in greatest dimension) in the upper pole of the left kidney.

Four months after the patient’s initial presentation, she was seen in the gynecology clinic of this hospital for a routine annual examination. She reported that pain in the left breast had developed 5 days earlier and that she had noted a lump in the upper outer quadrant. The pain had been persistent, was present throughout the breast, was worst near the nipple, and was unaffected by movement or change in position.

The patient had systemic lupus erythematosus with associated nephritis and chronic renal insufficiency, as well as cutaneous necrotizing vasculitis, urticarial vasculitis, Raynaud’s phenomenon, arthralgias, anemia, leukopenia, and a positive test for serum anticardiolipin antibodies. She also had migraine headaches, depression, gastritis, uterine fibroids, allergic rhinitis, gout, and lateral epicondylitis. Menarche had occurred when she was 11 years of age, and menopause when she was 47 years of age. The patient was nulliparous and had not taken hormone-replacement therapy. She had undergone surgery for skin ulcers on the legs 15 years earlier, bilateral cataract removal 14 years earlier, treatment for Helicobacter pylori infection 9 years earlier, endoscopic resection of a left nasopharyngeal cyst 5 years earlier, and arthroscopic surgery for right shoulder impingement syndrome and arthritis of the right acromioclavicular joint 4 years earlier. Medications included hydroxychloroquine, methylprednisolone, enalapril, metoprolol, calcium carbonate–ergocalciferol, aspirin, venlafaxine, omeprazole, and nasal ipratropium, as well as colchicine as needed. The patient had no known allergies to medications; leukopenia had occurred with the administration of mycophenolate. She had emigrated from Brazil 25 years earlier and frequently returned there to visit relatives and friends. She was unemployed and lived with a roommate in a suburban area of New England. She had smoked a half pack of cigarettes per day for 19 years but had stopped smoking 17 years before this evaluation. She drank alcohol on rare occasions and did not use illicit drugs. Her father had had diabetes mellitus, peptic ulcer disease, and nephrolithiasis and had died of sepsis; her mother had had hypertension and had died after a hip fracture. Her maternal grandfather had had gastric cancer, and a paternal aunt had had unspecified gynecologic cancer that was diagnosed when she was 38 years of age.

On examination, the patient appeared well. A firm, mildly tender mass (measuring 3 cm by 3 cm) was present in the left breast, between the 2 and 3 o’clock positions; it had no overlying skin abnormalities. A second, smaller mass was located at the 10 o’clock position. There was no nipple discharge or axillary lymphadenopathy. The right breast and the remainder of the physical examination were normal. Pathological examination of a specimen obtained during a Papanicolaou smear revealed atrophic changes and no evidence of an intraepithelial lesion or cancer.

Figure 2.

Imaging Studies of the Left Breast, Obtained at the Time of the Current Presentation.
Dr. Dang: Two days later, combined digital mammography and tomosynthesis revealed focal asymmetry in the upper outer quadrant of the left breast that had not been present on a previous mammogram and corresponded to the palpable abnormality (Figure 2); no suspicious masses, calcifications, or areas of architectural distortion were seen in the right breast. Ultrasonography targeted to the 2 o’clock position in the left breast revealed an irregular, hypoechoic mass (measuring 20 mm by 20 mm by 19 mm) located 9 cm from the nipple and situated in a background of tissue with heterogeneous echotexture that encompassed the majority of the upper outer quadrant (Figure 2).

Dr. Letourneau: Six days after the mammography and ultrasonography were performed, the patient was seen in the outpatient cancer center of this hospital. A lymph node was palpable in the left axilla. The remainder of the physical examination was unchanged.

A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 53-year-old woman with systemic lupus erythematosus with associated nephritis and chronic renal insufficiency was seen in the gynecology clinic of this hospital because of pain and a lump in the left breast.

Table 1.

Laboratory Data.
The patient had been in her usual health until 4 months before this presentation, when she noted a small, tender lump in the left breast on self-examination. Evaluation by her primary care physician revealed a firm, slightly mobile mass (measuring 5 mm in greatest dimension) in the upper inner quadrant of the left breast. The skin overlying the mass appeared normal, and there was no nipple discharge or axillary lymphadenopathy. The right breast and the remainder of the physical examination were normal. Three days earlier, routine laboratory tests had been performed by her nephrologist; the test results are shown in Table 1.

Figure 1.

Imaging Studies of the Left Breast, Obtained at the Time of the Initial Presentation.
Dr. Pragya A. Dang: Three days later, combined digital mammography and tomosynthesis of the left breast was negative, with no suspicious masses, areas of architectural distortion, or microcalcifications (Figure 1). Ultrasonography targeted to the 10 o’clock position in the left breast revealed a superficial, hyperechoic, oval mass (measuring 6 mm in greatest dimension) with circumscribed margins that was located 5 cm from the nipple, in the dermis. The radiologic differential diagnosis included a sebaceous cyst, and the mass was thought to be probably benign. A plan was made to perform follow-up imaging in 6 months.

Dr. Letourneau: Two months later, the patient was seen for routine follow-up in the nephrology and rheumatology clinics of this hospital. She reported fatigue, nausea, and epigastric pain. Mild epigastric tenderness was present; the remainder of the physical examination was normal. Laboratory test results are shown in Table 1. One month later, computed tomography of the abdomen and pelvis, performed without the administration of contrast material, revealed no evidence of pancreatitis; there was a new, indeterminate, hyperdense lesion (measuring 1.9 cm in greatest dimension) in the upper pole of the left kidney.

Four months after the patient’s initial presentation, she was seen in the gynecology clinic of this hospital for a routine annual examination. She reported that pain in the left breast had developed 5 days earlier and that she had noted a lump in the upper outer quadrant. The pain had been persistent, was present throughout the breast, was worst near the nipple, and was unaffected by movement or change in position.

The patient had systemic lupus erythematosus with associated nephritis and chronic renal insufficiency, as well as cutaneous necrotizing vasculitis, urticarial vasculitis, Raynaud’s phenomenon, arthralgias, anemia, leukopenia, and a positive test for serum anticardiolipin antibodies. She also had migraine headaches, depression, gastritis, uterine fibroids, allergic rhinitis, gout, and lateral epicondylitis. Menarche had occurred when she was 11 years of age, and menopause when she was 47 years of age. The patient was nulliparous and had not taken hormone-replacement therapy. She had undergone surgery for skin ulcers on the legs 15 years earlier, bilateral cataract removal 14 years earlier, treatment for Helicobacter pylori infection 9 years earlier, endoscopic resection of a left nasopharyngeal cyst 5 years earlier, and arthroscopic surgery for right shoulder impingement syndrome and arthritis of the right acromioclavicular joint 4 years earlier. Medications included hydroxychloroquine, methylprednisolone, enalapril, metoprolol, calcium carbonate–ergocalciferol, aspirin, venlafaxine, omeprazole, and nasal ipratropium, as well as colchicine as needed. The patient had no known allergies to medications; leukopenia had occurred with the administration of mycophenolate. She had emigrated from Brazil 25 years earlier and frequently returned there to visit relatives and friends. She was unemployed and lived with a roommate in a suburban area of New England. She had smoked a half pack of cigarettes per day for 19 years but had stopped smoking 17 years before this evaluation. She drank alcohol on rare occasions and did not use illicit drugs. Her father had had diabetes mellitus, peptic ulcer disease, and nephrolithiasis and had died of sepsis; her mother had had hypertension and had died after a hip fracture. Her maternal grandfather had had gastric cancer, and a paternal aunt had had unspecified gynecologic cancer that was diagnosed when she was 38 years of age.

On examination, the patient appeared well. A firm, mildly tender mass (measuring 3 cm by 3 cm) was present in the left breast, between the 2 and 3 o’clock positions; it had no overlying skin abnormalities. A second, smaller mass was located at the 10 o’clock position. There was no nipple discharge or axillary lymphadenopathy. The right breast and the remainder of the physical examination were normal. Pathological examination of a specimen obtained during a Papanicolaou smear revealed atrophic changes and no evidence of an intraepithelial lesion or cancer.

Figure 2.

Imaging Studies of the Left Breast, Obtained at the Time of the Current Presentation.
Dr. Dang: Two days later, combined digital mammography and tomosynthesis revealed focal asymmetry in the upper outer quadrant of the left breast that had not been present on a previous mammogram and corresponded to the palpable abnormality (Figure 2); no suspicious masses, calcifications, or areas of architectural distortion were seen in the right breast. Ultrasonography targeted to the 2 o’clock position in the left breast revealed an irregular, hypoechoic mass (measuring 20 mm by 20 mm by 19 mm) located 9 cm from the nipple and situated in a background of tissue with heterogeneous echotexture that encompassed the majority of the upper outer quadrant (Figure 2).

Dr. Letourneau: Six days after the mammography and ultrasonography were performed, the patient was seen in the outpatient cancer center of this hospital. A lymph node was palpable in the left axilla. The remainder of the physical examination was unchanged.

A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 53-year-old woman with a history of systemic lupus erythematosus, nephritis, and chronic renal insufficiency. She presents with a lump and pain in her left breast. The differential diagnosis for this patient includes breast cancer, fibroadenoma, breast cyst, and lupus mastitis. The patient's age and the presence of a new, palpable, firm mass in her breast that is associated with pain are concerning for breast cancer. However, the patient's history of lupus, a chronic inflammatory condition, could also be associated with lupus mastitis, a rare manifestation of lupus that can mimic breast cancer. Fibroadenomas and breast cysts are also possibilities, but these are less likely given the patient's age and the characteristics of the mass. The patient's imaging studies revealed an irregular, hypoechoic mass in the left breast, which is more suggestive of malignancy than a benign process. Therefore, the most likely diagnosis is breast cancer.\n\nDiagnosis: Breast Cancer""
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}",Breast Cancer,N
10.1056/NEJMcpc1609110,Case 28-2016 — A 31-Year-Old Woman with Infertility,,Primary infertility due to Mycobacterium tuberculosis infection.,Primary endometrial tuberculosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 31-year-old woman was seen in the outpatient fertility center of this hospital because of infertility.

During the previous 1.5 years, the patient had been well but unable to conceive. During the year before this evaluation, she was seen by physicians at another health care facility for evaluation of infertility.

Figure 1.

Hysterosalpingogram Obtained 9 Months before This Evaluation.
Dr. Aoife Kilcoyne: A hysterosalpingogram was obtained at another hospital 9 months before this evaluation (Figure 1). The uterine cavity had normal volume, symmetric contours, and no mucosal irregularity or filling defects. The proximal fallopian tubes filled promptly and were of normal thin, regular caliber, but the distal ampullary and infundibular portions were abnormally dilated and had multiple filling defects. Diverticular outpouchings in the ampullary and infundibular portions of the fallopian tubes were also seen. The lack of free spillage of contrast material into the peritoneal cavity was indicative of bilateral tubal occlusion.

Dr. Cardozo: The patient was referred to a fertility consultant at another facility, where she completed two cycles of in vitro fertilization; two high-quality embryos were transferred during each cycle, but there was no successful implantation or viable pregnancy. She was referred to the fertility center at this hospital.

The patient reported that menarche had occurred when she was 12 years of age. Her menstrual cycles were regular, were approximately 32 days long with a menstrual flow of 5 days’ duration, and were associated with minimal dysmenorrhea; her most recent menses had begun 24 days earlier. Results of a Papanicolaou (Pap) smear performed 13 months earlier were reportedly normal. She had no history of sexually transmitted diseases and had not been exposed to diethylstilbestrol. She had received the bacille Calmette–Guérin (BCG) vaccine as a child. Her only medication was a multivitamin. She had no known allergies. She drank alcohol infrequently and did not smoke or use illicit drugs. She had been married for 6 years and worked in an office.

The patient had been born and raised in Nepal and had most recently visited that country 4 months before this presentation. She had lived in India for 3 years and had immigrated to the United States 5 years earlier, where she had lived in the Southwest, a mid-Atlantic state, and most recently, New England. She exercised regularly, had a normal diet, and had no history of an eating disorder. Her father had hypertension, her maternal grandfather had colon cancer, and her maternal grandmother had diabetes mellitus; her mother and sibling were healthy.

On examination, the blood pressure was 110/70 mm Hg, the height 151 cm, the weight 49.5 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.7. The remainder of the examination was normal. A complete blood count, hemoglobin electrophoresis, and blood levels of thyrotropin and prolactin were normal. Tests for IgG antibodies to varicella and rubella were positive, and tests for antibodies to human immunodeficiency virus, hepatitis C virus, syphilis, and hepatitis B surface antigen were negative. The ABO blood type was A, Rh positive, with negative antibody screening.

Twenty-three days later, on day 3 of the patient’s menstrual cycle, an ultrasound-guided antral follicle count revealed multiple follicles (up to 15 mm in diameter) in each ovary and normal ovarian volume. The blood level of luteinizing hormone was 4.6 U per liter (reference range, 2.0 to 15.0 during the follicular phase, 22.0 to 105.0 during the ovulatory phase, and 0.6 to 19.0 during the luteal phase), the level of follicle-stimulating hormone was 3.8 U per liter (reference range, 3.0 to 20.0 during the follicular phase, 9.0 to 26.0 during the ovulatory phase, and 1.0 to 12.0 during the luteal phase), and the level of estradiol was 25 pg per milliliter (92 pmol per liter; reference range, <20.0 to 145.0 pg per milliliter [<73 to 532 pmol per liter] during the follicular phase, 112.0 to 443.0 pg per milliliter [411 to 1626 pmol per liter] during the midcycle peak, and <20.0 to 241.0 pg per milliliter [<73 to 885 pmol per liter] during the luteal phase).

Three days later, the patient returned to an outpatient clinic of this hospital. Testing for urinary human gonadotropin was negative. A pelvic examination, Pap smear, and cervical culture were performed. On hysteroscopic examination, the tubal ostia were well visualized and the uterine cavity appeared normal, with no evidence of intrauterine scar tissue, polyps, or fibroids. After the hysteroscopy, an endometrial biopsy was performed. Testing for Chlamydia trachomatis and Neisseria gonorrhoeae nucleic acids was negative.

Figure 2.

Endometrial-Biopsy Specimens (Hematoxylin and Eosin).
Dr. Drucilla J. Roberts: The pathology department received the endometrial-biopsy specimen, which consisted of an aggregate of hemorrhagic soft tissue (1 cm in greatest dimension), and the entire specimen was submitted for histologic processing. Hematoxylin and eosin staining of the tissue revealed weakly proliferative endometrium with multiple compact, nonnecrotizing granulomas (Figure 2). No polarizing material was present in the granulomas, and staining for acid-fast bacilli, Fite staining, and Grocott methenamine–silver staining showed no evidence of organisms.

Dr. Cardozo: Additional diagnostic procedures were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 31-year-old woman was seen in the outpatient fertility center of this hospital because of infertility.

During the previous 1.5 years, the patient had been well but unable to conceive. During the year before this evaluation, she was seen by physicians at another health care facility for evaluation of infertility.

Figure 1.

Hysterosalpingogram Obtained 9 Months before This Evaluation.
Dr. Aoife Kilcoyne: A hysterosalpingogram was obtained at another hospital 9 months before this evaluation (Figure 1). The uterine cavity had normal volume, symmetric contours, and no mucosal irregularity or filling defects. The proximal fallopian tubes filled promptly and were of normal thin, regular caliber, but the distal ampullary and infundibular portions were abnormally dilated and had multiple filling defects. Diverticular outpouchings in the ampullary and infundibular portions of the fallopian tubes were also seen. The lack of free spillage of contrast material into the peritoneal cavity was indicative of bilateral tubal occlusion.

Dr. Cardozo: The patient was referred to a fertility consultant at another facility, where she completed two cycles of in vitro fertilization; two high-quality embryos were transferred during each cycle, but there was no successful implantation or viable pregnancy. She was referred to the fertility center at this hospital.

The patient reported that menarche had occurred when she was 12 years of age. Her menstrual cycles were regular, were approximately 32 days long with a menstrual flow of 5 days’ duration, and were associated with minimal dysmenorrhea; her most recent menses had begun 24 days earlier. Results of a Papanicolaou (Pap) smear performed 13 months earlier were reportedly normal. She had no history of sexually transmitted diseases and had not been exposed to diethylstilbestrol. She had received the bacille Calmette–Guérin (BCG) vaccine as a child. Her only medication was a multivitamin. She had no known allergies. She drank alcohol infrequently and did not smoke or use illicit drugs. She had been married for 6 years and worked in an office.

The patient had been born and raised in Nepal and had most recently visited that country 4 months before this presentation. She had lived in India for 3 years and had immigrated to the United States 5 years earlier, where she had lived in the Southwest, a mid-Atlantic state, and most recently, New England. She exercised regularly, had a normal diet, and had no history of an eating disorder. Her father had hypertension, her maternal grandfather had colon cancer, and her maternal grandmother had diabetes mellitus; her mother and sibling were healthy.

On examination, the blood pressure was 110/70 mm Hg, the height 151 cm, the weight 49.5 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 21.7. The remainder of the examination was normal. A complete blood count, hemoglobin electrophoresis, and blood levels of thyrotropin and prolactin were normal. Tests for IgG antibodies to varicella and rubella were positive, and tests for antibodies to human immunodeficiency virus, hepatitis C virus, syphilis, and hepatitis B surface antigen were negative. The ABO blood type was A, Rh positive, with negative antibody screening.

Twenty-three days later, on day 3 of the patient’s menstrual cycle, an ultrasound-guided antral follicle count revealed multiple follicles (up to 15 mm in diameter) in each ovary and normal ovarian volume. The blood level of luteinizing hormone was 4.6 U per liter (reference range, 2.0 to 15.0 during the follicular phase, 22.0 to 105.0 during the ovulatory phase, and 0.6 to 19.0 during the luteal phase), the level of follicle-stimulating hormone was 3.8 U per liter (reference range, 3.0 to 20.0 during the follicular phase, 9.0 to 26.0 during the ovulatory phase, and 1.0 to 12.0 during the luteal phase), and the level of estradiol was 25 pg per milliliter (92 pmol per liter; reference range, <20.0 to 145.0 pg per milliliter [<73 to 532 pmol per liter] during the follicular phase, 112.0 to 443.0 pg per milliliter [411 to 1626 pmol per liter] during the midcycle peak, and <20.0 to 241.0 pg per milliliter [<73 to 885 pmol per liter] during the luteal phase).

Three days later, the patient returned to an outpatient clinic of this hospital. Testing for urinary human gonadotropin was negative. A pelvic examination, Pap smear, and cervical culture were performed. On hysteroscopic examination, the tubal ostia were well visualized and the uterine cavity appeared normal, with no evidence of intrauterine scar tissue, polyps, or fibroids. After the hysteroscopy, an endometrial biopsy was performed. Testing for Chlamydia trachomatis and Neisseria gonorrhoeae nucleic acids was negative.

Figure 2.

Endometrial-Biopsy Specimens (Hematoxylin and Eosin).
Dr. Drucilla J. Roberts: The pathology department received the endometrial-biopsy specimen, which consisted of an aggregate of hemorrhagic soft tissue (1 cm in greatest dimension), and the entire specimen was submitted for histologic processing. Hematoxylin and eosin staining of the tissue revealed weakly proliferative endometrium with multiple compact, nonnecrotizing granulomas (Figure 2). No polarizing material was present in the granulomas, and staining for acid-fast bacilli, Fite staining, and Grocott methenamine–silver staining showed no evidence of organisms.

Dr. Cardozo: Additional diagnostic procedures were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Tuberculosis of the fallopian tubes\n\nThe patient's history of living in Nepal and India, countries with high prevalence of tuberculosis, combined with the presence of nonnecrotizing granulomas in the endometrial biopsy, suggest a diagnosis of tuberculosis. The hysterosalpingogram showing bilateral tubal occlusion and the patient's infertility further support this diagnosis. Tuberculosis can cause infertility by damaging and blocking the fallopian tubes.""
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        ""content"": ""Tuberculosis of the fallopian tubes\n\nThe patient's history of living in Nepal and India, both high TB burden countries, along with the presence of non-necrotizing granulomas in the endometrial biopsy, are highly suggestive of tuberculosis. The hysterosalpingogram showing bilateral tubal occlusion and abnormal dilation of the fallopian tubes is consistent with tubal tuberculosis, a common cause of infertility in women. The absence of organisms in the biopsy does not rule out tuberculosis, as the bacteria are often difficult to detect directly.""
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        ""content"": ""Tuberculosis of the fallopian tubes\n\nThis patient presents with infertility and a history of living in Nepal and India, both countries with high prevalence of tuberculosis. The hysterosalpingogram shows bilateral tubal occlusion, which is a common finding in tubal tuberculosis. The endometrial biopsy shows non-necrotizing granulomas, which are characteristic of tuberculosis infection. Although the staining for acid-fast bacilli was negative, this does not rule out tuberculosis as the staining has low sensitivity. The patient's history of BCG vaccination as a child would not prevent her from contracting tuberculosis. Given the patient's history and the findings on imaging and biopsy, tuberculosis of the fallopian tubes is the most likely diagnosis.""
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10.1056/NEJMcpc1607091,"Case 27-2016 — A 71-Year-Old Woman with Müllerian Carcinoma, Fever, Fatigue, and Myalgias",,Transfusion-related babesiosis.,Transfusion-transmitted babesiosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 71-year-old woman with müllerian carcinoma was evaluated at this hospital during the fall because of fever, fatigue, and myalgias.

The patient had been well until 1 year before this evaluation, when explosive diarrhea developed. Examination of biopsy specimens obtained during flexible sigmoidoscopy and colonoscopy revealed evidence of microscopic colitis. Prednisone was administered, and the diarrhea resolved; after the prednisone therapy was tapered and then stopped, diarrhea recurred. Budesonide was prescribed.

Three months before this evaluation, the patient was seen at a local gastroenterology clinic. She had abdominal bloating and reported that reducing the dose of budesonide had been associated with recurrent diarrhea. She was following a lactose-free, gluten-free diet. On examination, the abdomen was distended and soft and had no masses. Budesonide was continued, and discontinuation of daily aspirin was recommended.

Table 1.

Laboratory Data.
Six weeks later and 6.5 weeks before this evaluation, the patient was seen by her primary care physician because of increased abdominal bloating, which was reported to be worse late in the day. She also reported that sexual intercourse had been difficult that week because her vagina seemed shorter. On examination, the abdomen was distended, with mild diffuse tenderness and slightly hyperactive bowel sounds. Results of a bimanual pelvic examination were normal. The erythrocyte sedimentation rate, anion gap, blood level of total bilirubin, and results of renal-function tests were normal; other laboratory test results are shown in Table 1. Four days later, imaging studies of the abdomen and pelvis were obtained.

Figure 1.

Imaging Studies of the Abdomen and Pelvis.
Dr. Kathryn P. Lowry: Computed tomography (CT) of the abdomen and pelvis, performed after the intravenous administration of contrast material, revealed moderate ascites (Figure 1A) and extensive peritoneal nodularity with omental caking (Figure 1B), findings consistent with peritoneal carcinomatosis. The ovaries were normal in size, and the uterus appeared enlarged (Figure 1C).

Dr. Panelli: Seven days later and 5 weeks before this evaluation, the patient was seen in the gynecologic oncology clinic at another hospital. Results of coagulation tests were normal; other laboratory test results are shown in Table 1. Ultrasound-guided paracentesis was performed, and cytologic examination of an aspirate of peritoneal fluid revealed adenocarcinoma, a finding that is most consistent with high-grade serous carcinoma of a gynecologic origin.

One week later and 4 weeks before this evaluation, the patient was seen in the gynecologic oncology surgery clinic at this hospital. She had a history of colitis, hypertension, type 1 second-degree atrioventricular block, the sick sinus syndrome, Sjögren’s syndrome, Raynaud’s phenomenon, atopy, chronic upper-airway cough syndrome, osteopenia, vitamin B12 deficiency, and glaucoma and had undergone laparoscopy with salpingectomy for an ectopic pregnancy. Medications included oral budesonide, diltiazem, cetirizine, and probiotics and intramuscular cyanocobalamin. She had allergies to tetracyclines, sulfamethoxazole, and latex; atorvastatin had caused elevated serum aminotransferase levels. The patient lived with her husband in a rural area of New England; she typically traveled to coastal New England during the summer but had not done so during the preceding year. She did not have pets. There was no family history of cancer.

On examination, the temperature was 37.3°C, the pulse 99 beats per minute, the blood pressure 169/91 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air. The weight was 49.3 kg. The abdomen was distended, and a fluid wave was present. The vaginal mucosa was atrophic, the uterus was anteverted and mobile, and there were no cul-de-sac nodularities or adnexal masses. The anion gap and results of coagulation and renal-function tests were normal, as were blood levels of magnesium, globulin, and total bilirubin; other laboratory test results are shown in Table 1.

Three days later and 3.5 weeks before this evaluation, the patient underwent surgical exploration and cytoreduction for a presumptive diagnosis of müllerian adenocarcinoma. Clindamycin and gentamicin were administered preoperatively; phenylephrine, insulin, calcium chloride, fentanyl, hydromorphone, lactated Ringer’s solution, albumin, and 3 units of packed red cells were administered during the procedure. Operative findings included approximately 2 liters of straw-colored ascitic fluid, tumor nodules in the splenic hilum and parenchyma and studding the right hemidiaphragm, replacement of the gastrocolic omentum by tumor, and obliteration of the cul-de-sac by a large pelvic mass invading and partially obstructing the rectosigmoid colon. Gastrocolic omentectomy, splenectomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, resections of the pelvic mass and rectosigmoid colon with primary reanastomosis, and plasma energy vaporization of tumor nodules on the right hemidiaphragm were performed. Resection specimens were submitted for histopathological examination.

Figure 2.

Specimen of the Resected Pelvic Mass.
Dr. Kristen M. Basnet: The primary resection specimen consisted of a 15.2-cm aggregate of large bowel, uterus, and adnexal structures that were firmly adherent one to another and contained a 15.0-cm irregular, firm, tan-white mass (Figure 2A). The cervix, the spleen, and portions of the omentum were submitted separately for examination. Microscopic examination revealed high-grade carcinoma in the ovaries, invading the muscularis propria of the large bowel (Figure 2B), and adjacent to the fallopian tubes (Figure 2C). The tumor was also seen adjacent to the uterine serosa and in the omentum, spleen, and mesentery of the transverse colon. The tumor was composed of nests and cords of pleomorphic cells with high mitotic activity (Figure 2D) and had slitlike spaces and psammomatous calcifications (Figure 2E). On immunohistochemical staining, the tumor cells were positive for PAX8 (Figure 2F) and negative for p53. The findings were consistent with high-grade carcinoma of müllerian origin. Müllerian carcinoma may most recognizably originate in a pelvic organ, such as the ovary, fallopian tube, or uterus, but it may also be found multifocally in the peritoneum without clear evidence of a particular site of origin, as was the case with this patient.

Dr. Panelli: The patient had persistent hypotension after surgery and was admitted to the surgical intensive care unit, where phenylephrine and mechanical ventilatory support were continued. A right pneumothorax was managed with chest-tube placement. On the first day after surgery, the trachea was extubated. The next day, phenylephrine was discontinued, 2 units of packed red cells were transfused, and the patient was transferred to the inpatient unit, where the chest tube was removed 1 day later. Quadrivalent meningococcal conjugate vaccine (serogroups A, C, Y, and W), 23-valent pneumococcal polysaccharide vaccine, and Haemophilus influenzae type b conjugate vaccine were administered. On the seventh day after surgery, the patient was discharged home.

Three days after discharge and 16 days before this evaluation, the patient was seen in the gynecologic oncology surgery clinic at this hospital for follow-up. She was thought to be recovering well, and the staples were removed from her surgical incision. A plan was made to schedule chemotherapy with paclitaxel and carboplatin at the other hospital.

Eighteen days after discharge and 1 day before this evaluation, the patient returned to the gynecologic oncology surgery clinic because of fatigue, anorexia, abdominal pain, bloating, and alternating constipation and diarrhea. She had not yet begun chemotherapy. She reported that abdominal pain and irregular bowel movements had been present since surgery and that the night before this presentation, she had tried medical marijuana, which she had obtained from a friend, as a treatment for pain before going to sleep. When she awoke 14 hours later, she felt drowsy and the abdominal pain persisted. Abdominal imaging was performed.

Figure 3.

Follow-up Imaging Studies.
Dr. Lowry: CT of the abdomen and pelvis, performed after the intravenous administration of contrast material, revealed postsurgical changes that had occurred since she had undergone the peritoneal cytoreduction, total hysterectomy, bilateral salpingo-oophorectomy, splenectomy, and rectosigmoid colon resection. Ascites had decreased, and only trace residual perihepatic fluid was present (Figure 3A). No abscesses were identified. There was no evidence of obstruction or inflammatory changes of the bowel (Figure 3B), and the rectosigmoid anastomosis was unremarkable in appearance (Figure 3C).

Dr. Panelli: The patient was admitted to the hospital. On admission, she reported feeling very tired. The temperature was 36.8°C, the pulse 97 beats per minute, the blood pressure 154/85 mm Hg, the respiratory rate 29 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. The abdomen was soft and mildly distended, without tenderness. The anion gap and results of renal-function tests were normal, as were blood levels of magnesium, globulin, and total bilirubin; other laboratory test results are shown in Table 1. Intravenous normal saline and oral senna, docusate, and magnesium citrate were administered.

By the second hospital day, the patient had had multiple bowel movements and the abdominal pain had decreased, but fatigue persisted and fever (to a temperature of 39.2°C), chills, myalgias, and subjective weakness developed. She underwent further evaluation. The pulse was 93 beats per minute, the blood pressure 138/64 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 95% while she was breathing ambient air. The remainder of the examination was unchanged.

Additional studies were performed, and the laboratory called with critical information that led to a presumptive diagnosis.

Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 71-year-old woman with müllerian carcinoma was evaluated at this hospital during the fall because of fever, fatigue, and myalgias.

The patient had been well until 1 year before this evaluation, when explosive diarrhea developed. Examination of biopsy specimens obtained during flexible sigmoidoscopy and colonoscopy revealed evidence of microscopic colitis. Prednisone was administered, and the diarrhea resolved; after the prednisone therapy was tapered and then stopped, diarrhea recurred. Budesonide was prescribed.

Three months before this evaluation, the patient was seen at a local gastroenterology clinic. She had abdominal bloating and reported that reducing the dose of budesonide had been associated with recurrent diarrhea. She was following a lactose-free, gluten-free diet. On examination, the abdomen was distended and soft and had no masses. Budesonide was continued, and discontinuation of daily aspirin was recommended.

Table 1.

Laboratory Data.
Six weeks later and 6.5 weeks before this evaluation, the patient was seen by her primary care physician because of increased abdominal bloating, which was reported to be worse late in the day. She also reported that sexual intercourse had been difficult that week because her vagina seemed shorter. On examination, the abdomen was distended, with mild diffuse tenderness and slightly hyperactive bowel sounds. Results of a bimanual pelvic examination were normal. The erythrocyte sedimentation rate, anion gap, blood level of total bilirubin, and results of renal-function tests were normal; other laboratory test results are shown in Table 1. Four days later, imaging studies of the abdomen and pelvis were obtained.

Figure 1.

Imaging Studies of the Abdomen and Pelvis.
Dr. Kathryn P. Lowry: Computed tomography (CT) of the abdomen and pelvis, performed after the intravenous administration of contrast material, revealed moderate ascites (Figure 1A) and extensive peritoneal nodularity with omental caking (Figure 1B), findings consistent with peritoneal carcinomatosis. The ovaries were normal in size, and the uterus appeared enlarged (Figure 1C).

Dr. Panelli: Seven days later and 5 weeks before this evaluation, the patient was seen in the gynecologic oncology clinic at another hospital. Results of coagulation tests were normal; other laboratory test results are shown in Table 1. Ultrasound-guided paracentesis was performed, and cytologic examination of an aspirate of peritoneal fluid revealed adenocarcinoma, a finding that is most consistent with high-grade serous carcinoma of a gynecologic origin.

One week later and 4 weeks before this evaluation, the patient was seen in the gynecologic oncology surgery clinic at this hospital. She had a history of colitis, hypertension, type 1 second-degree atrioventricular block, the sick sinus syndrome, Sjögren’s syndrome, Raynaud’s phenomenon, atopy, chronic upper-airway cough syndrome, osteopenia, vitamin B12 deficiency, and glaucoma and had undergone laparoscopy with salpingectomy for an ectopic pregnancy. Medications included oral budesonide, diltiazem, cetirizine, and probiotics and intramuscular cyanocobalamin. She had allergies to tetracyclines, sulfamethoxazole, and latex; atorvastatin had caused elevated serum aminotransferase levels. The patient lived with her husband in a rural area of New England; she typically traveled to coastal New England during the summer but had not done so during the preceding year. She did not have pets. There was no family history of cancer.

On examination, the temperature was 37.3°C, the pulse 99 beats per minute, the blood pressure 169/91 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air. The weight was 49.3 kg. The abdomen was distended, and a fluid wave was present. The vaginal mucosa was atrophic, the uterus was anteverted and mobile, and there were no cul-de-sac nodularities or adnexal masses. The anion gap and results of coagulation and renal-function tests were normal, as were blood levels of magnesium, globulin, and total bilirubin; other laboratory test results are shown in Table 1.

Three days later and 3.5 weeks before this evaluation, the patient underwent surgical exploration and cytoreduction for a presumptive diagnosis of müllerian adenocarcinoma. Clindamycin and gentamicin were administered preoperatively; phenylephrine, insulin, calcium chloride, fentanyl, hydromorphone, lactated Ringer’s solution, albumin, and 3 units of packed red cells were administered during the procedure. Operative findings included approximately 2 liters of straw-colored ascitic fluid, tumor nodules in the splenic hilum and parenchyma and studding the right hemidiaphragm, replacement of the gastrocolic omentum by tumor, and obliteration of the cul-de-sac by a large pelvic mass invading and partially obstructing the rectosigmoid colon. Gastrocolic omentectomy, splenectomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, resections of the pelvic mass and rectosigmoid colon with primary reanastomosis, and plasma energy vaporization of tumor nodules on the right hemidiaphragm were performed. Resection specimens were submitted for histopathological examination.

Figure 2.

Specimen of the Resected Pelvic Mass.
Dr. Kristen M. Basnet: The primary resection specimen consisted of a 15.2-cm aggregate of large bowel, uterus, and adnexal structures that were firmly adherent one to another and contained a 15.0-cm irregular, firm, tan-white mass (Figure 2A). The cervix, the spleen, and portions of the omentum were submitted separately for examination. Microscopic examination revealed high-grade carcinoma in the ovaries, invading the muscularis propria of the large bowel (Figure 2B), and adjacent to the fallopian tubes (Figure 2C). The tumor was also seen adjacent to the uterine serosa and in the omentum, spleen, and mesentery of the transverse colon. The tumor was composed of nests and cords of pleomorphic cells with high mitotic activity (Figure 2D) and had slitlike spaces and psammomatous calcifications (Figure 2E). On immunohistochemical staining, the tumor cells were positive for PAX8 (Figure 2F) and negative for p53. The findings were consistent with high-grade carcinoma of müllerian origin. Müllerian carcinoma may most recognizably originate in a pelvic organ, such as the ovary, fallopian tube, or uterus, but it may also be found multifocally in the peritoneum without clear evidence of a particular site of origin, as was the case with this patient.

Dr. Panelli: The patient had persistent hypotension after surgery and was admitted to the surgical intensive care unit, where phenylephrine and mechanical ventilatory support were continued. A right pneumothorax was managed with chest-tube placement. On the first day after surgery, the trachea was extubated. The next day, phenylephrine was discontinued, 2 units of packed red cells were transfused, and the patient was transferred to the inpatient unit, where the chest tube was removed 1 day later. Quadrivalent meningococcal conjugate vaccine (serogroups A, C, Y, and W), 23-valent pneumococcal polysaccharide vaccine, and Haemophilus influenzae type b conjugate vaccine were administered. On the seventh day after surgery, the patient was discharged home.

Three days after discharge and 16 days before this evaluation, the patient was seen in the gynecologic oncology surgery clinic at this hospital for follow-up. She was thought to be recovering well, and the staples were removed from her surgical incision. A plan was made to schedule chemotherapy with paclitaxel and carboplatin at the other hospital.

Eighteen days after discharge and 1 day before this evaluation, the patient returned to the gynecologic oncology surgery clinic because of fatigue, anorexia, abdominal pain, bloating, and alternating constipation and diarrhea. She had not yet begun chemotherapy. She reported that abdominal pain and irregular bowel movements had been present since surgery and that the night before this presentation, she had tried medical marijuana, which she had obtained from a friend, as a treatment for pain before going to sleep. When she awoke 14 hours later, she felt drowsy and the abdominal pain persisted. Abdominal imaging was performed.

Figure 3.

Follow-up Imaging Studies.
Dr. Lowry: CT of the abdomen and pelvis, performed after the intravenous administration of contrast material, revealed postsurgical changes that had occurred since she had undergone the peritoneal cytoreduction, total hysterectomy, bilateral salpingo-oophorectomy, splenectomy, and rectosigmoid colon resection. Ascites had decreased, and only trace residual perihepatic fluid was present (Figure 3A). No abscesses were identified. There was no evidence of obstruction or inflammatory changes of the bowel (Figure 3B), and the rectosigmoid anastomosis was unremarkable in appearance (Figure 3C).

Dr. Panelli: The patient was admitted to the hospital. On admission, she reported feeling very tired. The temperature was 36.8°C, the pulse 97 beats per minute, the blood pressure 154/85 mm Hg, the respiratory rate 29 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. The abdomen was soft and mildly distended, without tenderness. The anion gap and results of renal-function tests were normal, as were blood levels of magnesium, globulin, and total bilirubin; other laboratory test results are shown in Table 1. Intravenous normal saline and oral senna, docusate, and magnesium citrate were administered.

By the second hospital day, the patient had had multiple bowel movements and the abdominal pain had decreased, but fatigue persisted and fever (to a temperature of 39.2°C), chills, myalgias, and subjective weakness developed. She underwent further evaluation. The pulse was 93 beats per minute, the blood pressure 138/64 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 95% while she was breathing ambient air. The remainder of the examination was unchanged.

Additional studies were performed, and the laboratory called with critical information that led to a presumptive diagnosis.

Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Clostridium septicum bacteremia secondary to malignancy. The patient's symptoms of fever, fatigue, and myalgias, along with her history of m\u00fcllerian carcinoma, suggest an infection related to her cancer. Clostridium septicum is known to cause bacteremia in patients with malignancies, particularly gastrointestinal cancers. The patient's recent surgery and her symptoms of abdominal pain and irregular bowel movements could have provided an entry point for the bacteria. The critical information from the laboratory likely confirmed the presence of Clostridium septicum in her blood.""
      },
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        ""content"": ""The patient has a history of mullerian carcinoma and has recently undergone surgery for the same. She presents with fever, fatigue, and myalgias. Given her recent surgery and the presence of fever, a post-operative infection is a possibility. However, the CT scan does not show any abscesses or inflammatory changes of the bowel. The patient also has not started chemotherapy yet, ruling out chemotherapy-induced neutropenia and related infections. The patient's symptoms started after she tried medical marijuana. Given the temporal relationship and the absence of other clear causes, it is possible that the patient's symptoms are related to the use of medical marijuana. However, the critical information from the laboratory that led to a presumptive diagnosis is not provided in the case presentation, making it impossible to definitively diagnose the patient's condition. \n\nDiagnosis: \nUnable to determine without additional information.""
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}",Unable to determine without additional information,N,"{
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        ""content"": ""This is a 71-year-old woman with a history of mullerian carcinoma who presents with fever, fatigue, and myalgias. She also has a history of microscopic colitis, hypertension, type 1 second-degree atrioventricular block, the sick sinus syndrome, Sjogren's syndrome, Raynaud's phenomenon, atopy, chronic upper-airway cough syndrome, osteopenia, vitamin B12 deficiency, and glaucoma. She recently underwent surgical exploration and cytoreduction for her mullerian adenocarcinoma. The differential diagnosis for this patient includes post-operative infection, recurrence of her mullerian carcinoma, or a new malignancy. Given her recent surgery, a post-operative infection is a strong possibility. However, her symptoms of fever, fatigue, and myalgias are non-specific and could also be due to a recurrence of her mullerian carcinoma or a new malignancy. The patient's history of multiple autoimmune conditions also raises the possibility of an autoimmune flare. However, the onset of her symptoms after surgery and the presence of fever make an infection more likely.\n\nDiagnosis:\nPost-operative infection is the most likely diagnosis.""
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10.1056/NEJMcpc1505482,Case 26-2016 — A 28-Year-Old Woman with Back Pain and a Lesion in the Lumbar Spine,,Giant-cell tumor of bone.,Giant-cell tumor of bone.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 28-year-old woman was admitted to this hospital because of back pain and a lesion in the lumbar spine.

The patient had been well until approximately 6 months before admission, when low back pain developed and then worsened and could not be relieved by ibuprofen (at a dose of 800 mg every 6 hours, as needed). Approximately 6 weeks before admission, severe pain developed that radiated down her left leg to her ankle. She was seen by her primary care physician, and acetaminophen and hydrocodone were prescribed for 2 weeks; her condition did not improve. Approximately 1 month before admission, she was seen in the emergency department of another hospital, and prednisone was prescribed for 4 days, with transient improvement. She returned to her primary care physician’s office when the pain worsened. Imaging studies of the lumbar spine that had been performed at another hospital reportedly revealed destruction of the fifth lumbar vertebra (L5) and the presence of a large soft-tissue mass extending into the spinal canal and paraspinal soft tissues. Neurosurgical consultation was obtained. Ten days before admission, a biopsy of the lesion in the paravertebral region of the lumbar spine was performed.

Dr. Darcy A. Kerr: Pathological and cytologic examination of the biopsy specimen revealed a giant-cell tumor of bone.

Dr. Schwab: The patient was referred to the orthopedic oncology clinic of this hospital. On evaluation, she reported “excruciating” pain in her back that awakened her from sleep, radiated down her left leg, and was associated with swelling and numbness of the knee and distal leg but not with perineal numbness. She was primarily restricted to a wheelchair or bed because of the pain. She had mild constipation that she attributed to pain medications and no incontinence of urine or stool. She had migraine headaches and had had two previous episodes of transient lumbar back pain after motor vehicle accidents. Medications were gabapentin, ibuprofen, and oxycodone for pain, which she reportedly took sparingly. She was allergic to penicillin, which caused a rash. She had moved to the United States from the Caribbean as an infant, lived in an urban area with her boyfriend and child, and worked in retail. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her parents were living, and some of her relatives had high blood pressure and hypercholesterolemia.

On examination, the patient was in mild distress and walked with a limp. The blood pressure was 142/84 mm Hg, and the pulse 105 beats per minute; the temperature, respiratory rate, and oxygen saturation were normal. The left ilium and left lower lumbar spine were tender in response to palpation, and there was no palpable mass. The left foot was slightly cooler than the right; pedal pulses were present. Strength testing revealed 5/5 (normal) strength in all muscle groups on the right side, 4+/5 strength in the left iliopsoas and hamstrings, and 4/5 strength on abduction of the left hip. Strength was 5/5 bilaterally in the quadriceps, tibialis anterior, extensor hallucis longus, and gastrocnemius and soleus complex. The patient’s left leg had decreased sensation, particularly along the lateral thigh, medial and lateral calf, and dorsal and plantar aspects of the foot. The patellar and Achilles reflexes were 1+ bilaterally; the Babinski sign was not present. There was no clonus. Toe and heel walking were limited because of the pain in her back and leg. Active and passive straight-leg-raising tests induced radicular pain in the left leg. She had minimal pain when she performed the FABER (flexion, abduction, and external rotation of the hip) maneuver, and femoral nerve stretch testing was negative.

A complete blood count, white-cell differential count, and blood levels of electrolytes, calcium, glucose, urea nitrogen, and creatinine were normal. The patient was admitted to the hospital, and narcotic analgesic agents and gabapentin were administered for pain.

Figure 1.

Imaging Studies Obtained on Admission.
Dr. Daniel I. Rosenthal: Radiographs of the lumbosacral spine showed a lytic lesion involving L5. There was destruction of the left pedicle and central portions of the vertebral body (Figure 1A and 1B). Computed tomography (CT) and magnetic resonance imaging (MRI) of the lumbar spine revealed involvement of the lamina and a very large, hypervascular paraspinal mass. The mass extended into and filled the spinal canal (Figure 1C through 1F). The next day, CT of the chest revealed an indeterminate nodule (3 mm in diameter) in the left upper lobe but was otherwise normal. A radionuclide bone scan showed high uptake between L5 and the first sacral vertebra (S1).

Dr. Schwab: Management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 28-year-old woman was admitted to this hospital because of back pain and a lesion in the lumbar spine.

The patient had been well until approximately 6 months before admission, when low back pain developed and then worsened and could not be relieved by ibuprofen (at a dose of 800 mg every 6 hours, as needed). Approximately 6 weeks before admission, severe pain developed that radiated down her left leg to her ankle. She was seen by her primary care physician, and acetaminophen and hydrocodone were prescribed for 2 weeks; her condition did not improve. Approximately 1 month before admission, she was seen in the emergency department of another hospital, and prednisone was prescribed for 4 days, with transient improvement. She returned to her primary care physician’s office when the pain worsened. Imaging studies of the lumbar spine that had been performed at another hospital reportedly revealed destruction of the fifth lumbar vertebra (L5) and the presence of a large soft-tissue mass extending into the spinal canal and paraspinal soft tissues. Neurosurgical consultation was obtained. Ten days before admission, a biopsy of the lesion in the paravertebral region of the lumbar spine was performed.

Dr. Darcy A. Kerr: Pathological and cytologic examination of the biopsy specimen revealed a giant-cell tumor of bone.

Dr. Schwab: The patient was referred to the orthopedic oncology clinic of this hospital. On evaluation, she reported “excruciating” pain in her back that awakened her from sleep, radiated down her left leg, and was associated with swelling and numbness of the knee and distal leg but not with perineal numbness. She was primarily restricted to a wheelchair or bed because of the pain. She had mild constipation that she attributed to pain medications and no incontinence of urine or stool. She had migraine headaches and had had two previous episodes of transient lumbar back pain after motor vehicle accidents. Medications were gabapentin, ibuprofen, and oxycodone for pain, which she reportedly took sparingly. She was allergic to penicillin, which caused a rash. She had moved to the United States from the Caribbean as an infant, lived in an urban area with her boyfriend and child, and worked in retail. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her parents were living, and some of her relatives had high blood pressure and hypercholesterolemia.

On examination, the patient was in mild distress and walked with a limp. The blood pressure was 142/84 mm Hg, and the pulse 105 beats per minute; the temperature, respiratory rate, and oxygen saturation were normal. The left ilium and left lower lumbar spine were tender in response to palpation, and there was no palpable mass. The left foot was slightly cooler than the right; pedal pulses were present. Strength testing revealed 5/5 (normal) strength in all muscle groups on the right side, 4+/5 strength in the left iliopsoas and hamstrings, and 4/5 strength on abduction of the left hip. Strength was 5/5 bilaterally in the quadriceps, tibialis anterior, extensor hallucis longus, and gastrocnemius and soleus complex. The patient’s left leg had decreased sensation, particularly along the lateral thigh, medial and lateral calf, and dorsal and plantar aspects of the foot. The patellar and Achilles reflexes were 1+ bilaterally; the Babinski sign was not present. There was no clonus. Toe and heel walking were limited because of the pain in her back and leg. Active and passive straight-leg-raising tests induced radicular pain in the left leg. She had minimal pain when she performed the FABER (flexion, abduction, and external rotation of the hip) maneuver, and femoral nerve stretch testing was negative.

A complete blood count, white-cell differential count, and blood levels of electrolytes, calcium, glucose, urea nitrogen, and creatinine were normal. The patient was admitted to the hospital, and narcotic analgesic agents and gabapentin were administered for pain.

Figure 1.

Imaging Studies Obtained on Admission.
Dr. Daniel I. Rosenthal: Radiographs of the lumbosacral spine showed a lytic lesion involving L5. There was destruction of the left pedicle and central portions of the vertebral body (Figure 1A and 1B). Computed tomography (CT) and magnetic resonance imaging (MRI) of the lumbar spine revealed involvement of the lamina and a very large, hypervascular paraspinal mass. The mass extended into and filled the spinal canal (Figure 1C through 1F). The next day, CT of the chest revealed an indeterminate nodule (3 mm in diameter) in the left upper lobe but was otherwise normal. A radionuclide bone scan showed high uptake between L5 and the first sacral vertebra (S1).

Dr. Schwab: Management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Giant Cell Tumor of Bone\n\nThe patient's symptoms of back pain and radiating leg pain, along with the imaging studies showing a lytic lesion involving L5 and a large, hypervascular paraspinal mass, suggest a spinal tumor. The biopsy confirmed the diagnosis of a giant cell tumor of bone. These tumors are generally benign but can be locally aggressive and cause significant morbidity due to their location and size.""
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        ""content"": ""Giant cell tumor of the bone. The patient's symptoms of severe back pain, radiating pain down the leg, and numbness, along with imaging studies showing a lytic lesion involving L5 and a large, hypervascular paraspinal mass, are consistent with this diagnosis. The pathological and cytologic examination of the biopsy specimen further confirmed the diagnosis.""
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10.1056/NEJMcpc1602815,Case 25-2016 — A 33-Year-Old Man with Rectal Pain and Bleeding,,Syphilitic proctitis.,Syphilitic proctitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 33-year-old man was seen in the surgery clinic of this hospital because of painful bowel movements and rectal bleeding.

The patient had been well until approximately 4 months before this presentation, when pain with defecation developed. He typically had one bowel movement each day and noted bright red blood on the toilet paper after wiping, although blood did not appear to be mixed in with the stool itself. The patient had not had abdominal pain or weight loss. On the sixth day of illness, he was seen by his primary care physician. The patient reported that he had had a sexual encounter with a man approximately 6 weeks earlier. On examination, a tender external hemorrhoid was noted; the vital signs and the remainder of the examination were normal. Tests were negative for hepatitis B surface antigen and antibodies to hepatitis B virus, hepatitis C virus, and the human immunodeficiency virus (HIV). Psyllium, naproxen, and topical hydrocortisone cream were prescribed.

Approximately 10 weeks later, the patient returned to the primary care clinic and reported that rectal pain and bleeding with defecation had persisted. On examination, the patient appeared well. The temperature was 36.4°C, the pulse 82 beats per minute, and the blood pressure 126/76 mm Hg. Bleeding hemorrhoids were noted around the anal opening; the remainder of the examination was normal. Psyllium, naproxen, and topical hydrocortisone cream were continued, and the patient was referred to the colorectal surgery clinic at this hospital.

At the surgery clinic, the patient reported that the rectal pain and bleeding persisted and that he had not noted any protrusion of tissue through the anus. His medications included naproxen, as needed, and hydrocortisone cream applied topically to the anus, which had provided only minimal pain relief. He had no known allergies. He had emigrated from Brazil 16 years earlier and now lived with his wife in an urban area of New England. He worked in construction and did not smoke tobacco. He was bisexual; he reported that he had never had a sexually transmitted infection. His mother had hypertension. There was no family history of colorectal cancer.

The patient appeared well. Examination of the neck, heart, lungs, and abdomen was normal. At the anterior and posterior midline anal verge, there were large, superficial anal fissures and small-to-moderate-sized distal sentinel skin tags. Results of a digital rectal examination were normal except for the presence of moderate tenderness. Anoscopy revealed the fissures and small internal hemorrhoids. Flexible sigmoidoscopy was performed, with insertion of the sigmoidoscope to a depth of 30 cm; mild-to-moderate mucosal inflammation of the most distal 10 cm of the rectum was present and was characterized by edema and patchy erythema.

A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 33-year-old man was seen in the surgery clinic of this hospital because of painful bowel movements and rectal bleeding.

The patient had been well until approximately 4 months before this presentation, when pain with defecation developed. He typically had one bowel movement each day and noted bright red blood on the toilet paper after wiping, although blood did not appear to be mixed in with the stool itself. The patient had not had abdominal pain or weight loss. On the sixth day of illness, he was seen by his primary care physician. The patient reported that he had had a sexual encounter with a man approximately 6 weeks earlier. On examination, a tender external hemorrhoid was noted; the vital signs and the remainder of the examination were normal. Tests were negative for hepatitis B surface antigen and antibodies to hepatitis B virus, hepatitis C virus, and the human immunodeficiency virus (HIV). Psyllium, naproxen, and topical hydrocortisone cream were prescribed.

Approximately 10 weeks later, the patient returned to the primary care clinic and reported that rectal pain and bleeding with defecation had persisted. On examination, the patient appeared well. The temperature was 36.4°C, the pulse 82 beats per minute, and the blood pressure 126/76 mm Hg. Bleeding hemorrhoids were noted around the anal opening; the remainder of the examination was normal. Psyllium, naproxen, and topical hydrocortisone cream were continued, and the patient was referred to the colorectal surgery clinic at this hospital.

At the surgery clinic, the patient reported that the rectal pain and bleeding persisted and that he had not noted any protrusion of tissue through the anus. His medications included naproxen, as needed, and hydrocortisone cream applied topically to the anus, which had provided only minimal pain relief. He had no known allergies. He had emigrated from Brazil 16 years earlier and now lived with his wife in an urban area of New England. He worked in construction and did not smoke tobacco. He was bisexual; he reported that he had never had a sexually transmitted infection. His mother had hypertension. There was no family history of colorectal cancer.

The patient appeared well. Examination of the neck, heart, lungs, and abdomen was normal. At the anterior and posterior midline anal verge, there were large, superficial anal fissures and small-to-moderate-sized distal sentinel skin tags. Results of a digital rectal examination were normal except for the presence of moderate tenderness. Anoscopy revealed the fissures and small internal hemorrhoids. Flexible sigmoidoscopy was performed, with insertion of the sigmoidoscope to a depth of 30 cm; mild-to-moderate mucosal inflammation of the most distal 10 cm of the rectum was present and was characterized by edema and patchy erythema.

A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of painful bowel movements and rectal bleeding, along with the physical examination findings of anal fissures and small internal hemorrhoids, suggest a diagnosis of anal fissures and hemorrhoids. The patient's sexual history and the presence of mucosal inflammation in the rectum could suggest a sexually transmitted infection, but tests for hepatitis B, hepatitis C, and HIV were negative. The patient's symptoms did not improve with conservative treatment, including fiber supplementation and topical hydrocortisone, which is commonly used for hemorrhoids. The presence of mucosal inflammation in the rectum could also suggest inflammatory bowel disease, but the patient does not have other symptoms such as abdominal pain or weight loss. Therefore, the most likely diagnosis is anal fissures and hemorrhoids.\n\nDiagnosis: Anal fissures and hemorrhoids.""
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      ""index"": 0,
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        ""role"": ""assistant"",
        ""content"": ""The patient's symptoms of painful bowel movements and rectal bleeding, along with the physical examination findings of anal fissures and small internal hemorrhoids, suggest a diagnosis of anal fissures and hemorrhoids. The patient's sexual history and the presence of mucosal inflammation in the rectum could suggest a sexually transmitted infection, but tests for hepatitis B, hepatitis C, and HIV were negative. The patient's symptoms did not improve with conservative treatment, including fiber supplementation and topical hydrocortisone, which is commonly used for hemorrhoids and anal fissures. The absence of other gastrointestinal symptoms such as abdominal pain or weight loss makes other diagnoses such as inflammatory bowel disease or colorectal cancer less likely.\n\nDiagnosis: Anal fissures and hemorrhoids.""
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    {
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        ""role"": ""assistant"",
        ""content"": ""The patient is a 33-year-old man presenting with painful bowel movements and rectal bleeding. The differential diagnosis for these symptoms includes hemorrhoids, anal fissures, colorectal cancer, and sexually transmitted infections such as gonorrhea or chlamydia. The patient's history of a recent sexual encounter with a man and his report of rectal pain and bleeding could suggest a sexually transmitted infection, but tests for hepatitis B, hepatitis C, and HIV were negative. The patient's age and lack of family history of colorectal cancer make this diagnosis less likely. The patient's symptoms have persisted despite treatment for hemorrhoids, suggesting that this may not be the correct diagnosis. The physical examination revealed large, superficial anal fissures and small-to-moderate-sized distal sentinel skin tags, as well as mild-to-moderate mucosal inflammation of the most distal 10 cm of the rectum characterized by edema and patchy erythema. These findings are consistent with anal fissures and proctitis.\n\nDiagnosis: Anal fissures and proctitis.""
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 10.1056/NEJMcpc1503829,"Case 24-2016 — A 66-Year-Old Man with Malaise, Weakness, and Hypercalcemia",,The milk alkali syndrome.,"Hypercalcemia due to the milk alkali syndrome and exacerbated by the use of hydrochlorothiazide.

Acute kidney injury due to hypercalcemia and the combination of diuretics and nonsteroidal antiinflammatory drugs.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 66-year-old man was admitted to this hospital because of malaise, weakness, and hypercalcemia.

Thirty-five hours before admission, the patient was seen in an outpatient clinic affiliated with this hospital for evaluation of multiple problems, including a 3-week history of mild pain in the shoulder and left side of the neck, a 2-month history of muscle pain in the left leg that had occurred after a sports injury, listlessness, and a 3-month history of increasing frequency of urination, which occurred in small amounts up to twice each night and every 3 hours during the day and for which he had begun to restrict fluid. His neck pain had developed at work. Examination of the neck had revealed trapezius muscle spasm; naproxen, acetaminophen, and cyclobenzaprine had been administered, and the pain partially decreased.

He also had a history of hypertension, benign prostatic hypertrophy, diverticulitis, lumbar disk disease, colonic polyps, ischial bursitis, chronic dyspepsia, nocturnal leg cramps, excessive alcohol use, and osteoarthritis of the shoulders, knees, and hips. Medications were amlodipine, hydrochlorothiazide, aspirin, calcium carbonate for dyspepsia, tamsulosin, n–3 fatty acids, glucosamine, and a multivitamin, as well as ibuprofen and naproxen for musculoskeletal symptoms and, as needed, tadalafil and disulfiram. He had no known medication allergies.

Table 1.

Laboratory Data.
On examination, the patient appeared to be comfortable. The temperature was 36.7°C, the blood pressure 120/80 mm Hg, the pulse 108 beats per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 31.2. The posterior neck and occipital region on the left side were tender but had full range of motion, and the remainder of the examination was normal. The platelet count, red-cell indexes, and blood levels of glucose, thyrotropin, aspartate aminotransferase, and alanine aminotransferase were normal; other test results are shown in Table 1. Examination of the urine revealed turbid yellow fluid that was otherwise normal; urine culture was negative. That evening, after results of the blood tests were known, the patient was contacted and asked to return the next day for additional testing.

Approximately 26 hours after the initial laboratory tests, the additional testing was performed. The blood levels of glucose, total protein, albumin, globulin, total bilirubin, lactate dehydrogenase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were normal; other test results are shown in Table 1. Eight hours later, when the test results were known, the patient was advised to go to the emergency department of this hospital for evaluation of potentially life-threatening abnormalities, and he was subsequently admitted.

In the emergency department, the patient reported residual stiffness of the neck. He had had an influenza-like illness (with subjective fevers, diaphoresis, and nasal congestion) approximately 3 weeks before this evaluation that resolved spontaneously, and he reported chronic constipation that was unchanged. He had stopped drinking alcohol 4 years earlier and did not smoke tobacco or use illicit drugs. He lived with his wife, had adult children, and worked in an office. His father and a grandfather had died of lung cancer, a grandmother had died of a stroke, his mother had died of liver disease, and an uncle had had pancreatic cancer.

On examination, the temperature was 36.8°C, the blood pressure 159/114 mm Hg, the pulse 109 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The remainder of the examination was normal. An electrocardiogram showed sinus rhythm with a ventricular rate of 101 beats per minute, a PR interval of 260 msec, a QRS complex of 136 msec, and a ratio of QT interval to QT interval corrected for heart rate of 318:412 msec; first-degree atrioventricular block and right bundle-branch block were present and had not been present 3 years earlier. A chest radiograph showed clear lungs and degenerative changes of the spine. The platelet count, prothrombin time, and prothrombin-time international normalized ratio were normal, as were blood levels of glucose, phosphorus, lactic acid, magnesium, total protein, albumin, globulin, total and direct bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lipase, troponin T, and N-terminal pro–B-type natriuretic peptide; other test results are shown in Table 1. Urinalysis revealed yellow, slightly cloudy urine, with a pH of 9.0, a specific gravity of 1.006, and 1+ occult blood by dipstick, as well as 0 to 2 red cells and 3 to 5 white cells per high-power field; squamous cells were present. The patient was admitted to the hospital, and additional imaging studies were obtained.

Figure 1.

CT Scan of the Chest.
Figure 2.

Radionuclide Bone Scan.
Dr. William E. Palmer: Computed tomography (CT) of the abdomen and pelvis, performed without the administration of intravenous or oral contrast material, revealed no evidence of cancer. CT of the chest revealed an indeterminate sclerotic lesion involving the right eighth rib (Figure 1). A radionuclide bone scan was recommended as a screening study for additional skeletal lesions. The bone scan revealed nonspecific abnormal uptake by the rib lesion and at the left ischium (Figure 2). Because there were concerns about cancer, magnetic resonance imaging (MRI) of the pelvis was recommended for further evaluation and revealed a high-grade tear of the left common hamstring tendon at the ischial tuberosity attachment site. A fluoroscopically guided glucocorticoid injection had been performed at this location 11 months earlier.

Dr. Gupta: Additional tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 66-year-old man was admitted to this hospital because of malaise, weakness, and hypercalcemia.

Thirty-five hours before admission, the patient was seen in an outpatient clinic affiliated with this hospital for evaluation of multiple problems, including a 3-week history of mild pain in the shoulder and left side of the neck, a 2-month history of muscle pain in the left leg that had occurred after a sports injury, listlessness, and a 3-month history of increasing frequency of urination, which occurred in small amounts up to twice each night and every 3 hours during the day and for which he had begun to restrict fluid. His neck pain had developed at work. Examination of the neck had revealed trapezius muscle spasm; naproxen, acetaminophen, and cyclobenzaprine had been administered, and the pain partially decreased.

He also had a history of hypertension, benign prostatic hypertrophy, diverticulitis, lumbar disk disease, colonic polyps, ischial bursitis, chronic dyspepsia, nocturnal leg cramps, excessive alcohol use, and osteoarthritis of the shoulders, knees, and hips. Medications were amlodipine, hydrochlorothiazide, aspirin, calcium carbonate for dyspepsia, tamsulosin, n–3 fatty acids, glucosamine, and a multivitamin, as well as ibuprofen and naproxen for musculoskeletal symptoms and, as needed, tadalafil and disulfiram. He had no known medication allergies.

Table 1.

Laboratory Data.
On examination, the patient appeared to be comfortable. The temperature was 36.7°C, the blood pressure 120/80 mm Hg, the pulse 108 beats per minute, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 31.2. The posterior neck and occipital region on the left side were tender but had full range of motion, and the remainder of the examination was normal. The platelet count, red-cell indexes, and blood levels of glucose, thyrotropin, aspartate aminotransferase, and alanine aminotransferase were normal; other test results are shown in Table 1. Examination of the urine revealed turbid yellow fluid that was otherwise normal; urine culture was negative. That evening, after results of the blood tests were known, the patient was contacted and asked to return the next day for additional testing.

Approximately 26 hours after the initial laboratory tests, the additional testing was performed. The blood levels of glucose, total protein, albumin, globulin, total bilirubin, lactate dehydrogenase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were normal; other test results are shown in Table 1. Eight hours later, when the test results were known, the patient was advised to go to the emergency department of this hospital for evaluation of potentially life-threatening abnormalities, and he was subsequently admitted.

In the emergency department, the patient reported residual stiffness of the neck. He had had an influenza-like illness (with subjective fevers, diaphoresis, and nasal congestion) approximately 3 weeks before this evaluation that resolved spontaneously, and he reported chronic constipation that was unchanged. He had stopped drinking alcohol 4 years earlier and did not smoke tobacco or use illicit drugs. He lived with his wife, had adult children, and worked in an office. His father and a grandfather had died of lung cancer, a grandmother had died of a stroke, his mother had died of liver disease, and an uncle had had pancreatic cancer.

On examination, the temperature was 36.8°C, the blood pressure 159/114 mm Hg, the pulse 109 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The remainder of the examination was normal. An electrocardiogram showed sinus rhythm with a ventricular rate of 101 beats per minute, a PR interval of 260 msec, a QRS complex of 136 msec, and a ratio of QT interval to QT interval corrected for heart rate of 318:412 msec; first-degree atrioventricular block and right bundle-branch block were present and had not been present 3 years earlier. A chest radiograph showed clear lungs and degenerative changes of the spine. The platelet count, prothrombin time, and prothrombin-time international normalized ratio were normal, as were blood levels of glucose, phosphorus, lactic acid, magnesium, total protein, albumin, globulin, total and direct bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lipase, troponin T, and N-terminal pro–B-type natriuretic peptide; other test results are shown in Table 1. Urinalysis revealed yellow, slightly cloudy urine, with a pH of 9.0, a specific gravity of 1.006, and 1+ occult blood by dipstick, as well as 0 to 2 red cells and 3 to 5 white cells per high-power field; squamous cells were present. The patient was admitted to the hospital, and additional imaging studies were obtained.

Figure 1.

CT Scan of the Chest.
Figure 2.

Radionuclide Bone Scan.
Dr. William E. Palmer: Computed tomography (CT) of the abdomen and pelvis, performed without the administration of intravenous or oral contrast material, revealed no evidence of cancer. CT of the chest revealed an indeterminate sclerotic lesion involving the right eighth rib (Figure 1). A radionuclide bone scan was recommended as a screening study for additional skeletal lesions. The bone scan revealed nonspecific abnormal uptake by the rib lesion and at the left ischium (Figure 2). Because there were concerns about cancer, magnetic resonance imaging (MRI) of the pelvis was recommended for further evaluation and revealed a high-grade tear of the left common hamstring tendon at the ischial tuberosity attachment site. A fluoroscopically guided glucocorticoid injection had been performed at this location 11 months earlier.

Dr. Gupta: Additional tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Multiple Myeloma. The patient's hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB criteria) are indicative of multiple myeloma. The presence of a monoclonal protein (M protein) in the blood or urine is a key feature of this disease. The patient's age and history of bone pain also align with this diagnosis.""
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        ""content"": ""The patient's symptoms of malaise, weakness, and hypercalcemia, along with the presence of a sclerotic lesion in the right eighth rib and abnormal uptake in the left ischium on a radionuclide bone scan, suggest the possibility of a malignancy. However, the CT scan of the abdomen and pelvis showed no evidence of cancer. The patient's history of excessive alcohol use and the presence of first-degree atrioventricular block and right bundle-branch block on the electrocardiogram could suggest cardiac involvement. However, the most striking abnormality is the hypercalcemia. Hypercalcemia can be caused by several conditions, including hyperparathyroidism, malignancy, and certain medications. Given the patient's age, history, and the presence of a sclerotic lesion, malignancy-associated hypercalcemia is a strong possibility. This could be due to a paraneoplastic syndrome, in which a tumor produces a hormone (in this case, parathyroid hormone-related protein) that causes hypercalcemia. The absence of abdominal or pelvic cancer on CT scan does not rule out other types of cancer, such as multiple myeloma, which can cause lytic or sclerotic bone lesions and hypercalcemia. \n\nDiagnosis: Multiple Myeloma""
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        ""content"": ""The patient is a 66-year-old man presenting with malaise, weakness, and hypercalcemia. His history includes hypertension, benign prostatic hypertrophy, diverticulitis, lumbar disk disease, colonic polyps, ischial bursitis, chronic dyspepsia, nocturnal leg cramps, excessive alcohol use, and osteoarthritis of the shoulders, knees, and hips. The differential diagnosis for this patient includes malignancy, hyperparathyroidism, sarcoidosis, and multiple myeloma. The patient's history of alcohol use and multiple health problems could suggest a malignancy. However, his lab results do not show any signs of anemia, which would be expected in a patient with cancer. Hyperparathyroidism could also cause hypercalcemia, but the patient's parathyroid hormone level is not elevated, which makes this diagnosis less likely. Sarcoidosis could also cause hypercalcemia, but the patient does not have any respiratory symptoms, which are common in sarcoidosis. Multiple myeloma could also cause hypercalcemia, and the patient's age and symptoms of malaise and weakness could be consistent with this diagnosis. The patient's lab results show an elevated total protein level and an abnormal protein electrophoresis, which could suggest multiple myeloma. Additionally, the patient's CT scan shows a sclerotic lesion on the right eighth rib, which could be a lytic lesion from multiple myeloma. \n\nDiagnosis: Multiple Myeloma.""
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10.1056/NEJMcpc1601840,Case 23-2016 — A 46-Year-Old Man with Somnolence after Orthopedic Surgery,,The fat embolism syndrome.,The fat embolism syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 46-year-old man with myxoid chondrosarcoma of the left femur was evaluated by the internal medicine consult service because he had worsening somnolence 1 day after he underwent proximal femoral replacement surgery.

The patient had been well until 5 weeks before this evaluation, when he slipped and fell onto the pavement during a vacation in Haiti. Left hip pain developed immediately, and he had difficulty getting up after the fall. The patient rested and took ibuprofen, but the pain did not decrease.

Two weeks later, after returning to the United States, the patient went to the emergency department of another hospital and reported that the pain had progressively increased and that he was unable to bear weight on the left leg. He had been previously healthy, was taking no medications, and had no known allergies. He lived in an urban area of New England with his girlfriend, drove a bus, and did not smoke tobacco, drink alcohol, or use illicit drugs. He was born in Haiti and had returned there frequently after moving to New England during childhood. His father had hypertension and diabetes mellitus; there was no known family history of bone or soft-tissue cancer or of venous thromboembolism. On examination, the blood pressure was 154/99 mm Hg, and the other vital signs were normal. There was tenderness over the greater trochanter of the left femur, and the pain increased with rotation of the left hip. Imaging studies were obtained.

Figure 1.

Radiograph of the Left Hip.
Dr. R. Gilberto Gonzalez: A frontal radiograph showed a lytic lesion, measuring 4.8 cm by 3.9 cm, involving the left femoral neck and greater trochanter, with cortical thinning (Figure 1). A region of cortical discontinuity raised concerns about cortical breakthrough or a pathologic fracture.

Dr. Scott: The patient was admitted to the other hospital, and ibuprofen, oxycodone, enoxaparin, amlodipine, docusate, and senna were administered. On the fourth hospital day, the patient was discharged home and advised to follow up with an orthopedic surgeon at this hospital.

The patient was seen in the orthopedic surgery clinic 3 weeks after he had fallen. He reported that the pain had decreased but continued to be present during ambulation and when he slept on his left side. On examination, there was tenderness in response to deep palpation over the greater trochanter of the left femur. A computed tomography (CT)–guided core-needle biopsy of the lytic bone lesion was performed; histopathological examination of the biopsy specimen revealed myxoid chondrosarcoma.

Table 1.

Laboratory Data.
Four weeks after the patient had fallen, he returned to the orthopedic surgery clinic and reported that the pain persisted but had decreased in severity. Laboratory test results are shown in Table 1. A CT scan of the chest, obtained after the administration of intravenous contrast material, showed no evidence of thoracic metastases. Surgical resection of the femoral tumor was scheduled for the following week.

The day before this evaluation, the patient underwent proximal femoral replacement surgery; the left proximal femur was resected, and the hip was reconstructed with the use of a cementless bipolar endoprosthetic implant. The procedure was complicated by a posteriorly oriented crack in the femur that occurred during implantation of the prosthesis.

Figure 2.

Resection Specimen of the Proximal Left Femur.
Dr. Vikram Deshpande: The resection specimen showed myxoid chondrosarcoma (grade 2/3). On macroscopic examination, the tumor measured 3.5 cm by 3.0 cm by 2.5 cm and involved the neck and greater trochanter of the femur (Figure 2A). The tumor infiltrated adjacent cortical and cancellous bone (Figure 2B) and was composed of mononucleate and binucleate cells embedded in abundant myxoid stroma (Figure 2C). On immunohistochemical staining for S100, the tumor cells were diffusely and strongly positive; this nonspecific stain is positive in virtually all cartilaginous cancers, including chondroblastic osteosarcoma. The tumor was accompanied by a fracture callus (Figure 2D). There was no evidence of vascular invasion, and all resected margins were negative for tumor.

Dr. Scott: After completion of the surgery, the patient was transferred to the postanesthesia care unit, where he was initially sleepy but arousable; within 2 hours, he was alert and oriented to person, place, and time, as well as responding appropriately to questions and using patient-controlled analgesia with a morphine infusion pump. Laboratory test results are shown in Table 1. Postoperative radiographs of the left hip and femur showed a nondisplaced fracture of the distal femoral diaphysis extending from the distal tip of the femoral implant to the distal femoral metaphysis. The patient was transferred to the inpatient unit.

The next morning, 12 hours after the conclusion of surgery, the patient reported that his pain was well controlled. Two hours later, he was noted to be drowsier and less interactive. He neither spoke spontaneously nor responded verbally to questions, and he opened his eyes only intermittently when he was spoken to by caregivers. Tachycardia developed; the pulse was 110 beats per minute. Laboratory test results are shown in Table 1. Magnesium sulfate was administered. Sixteen hours after the conclusion of surgery, use of the morphine infusion pump was discontinued. The patient became increasingly somnolent. Two hours later, naloxone was administered; there was a mild, transient increase in eye opening and an increase in heart rate to 137 beats per minute, and hypertension developed, with a blood pressure of 202/107 mm Hg. Metoprolol was administered; the pulse decreased to 106 beats per minute, and the blood pressure to 143/83 mm Hg. The temperature was 38.9°C. Laboratory test results obtained 24 hours after the conclusion of surgery are shown in Table 1.

Dr. Gonzalez: CT of the head, performed without the administration of intravenous contrast material, revealed no evidence of acute intracranial hemorrhage, territorial infarction, or intracranial mass lesion.

Dr. Scott: Medical consultation was requested for persistent somnolence. On evaluation by the consulting physician, the patient was unable to answer any questions. Medications included enoxaparin, amlodipine, a multivitamin, and intravenous fluids. On examination, the temperature was 37.7°C, the pulse 121 beats per minute, the blood pressure 135/89 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation between 95% and 97% while the patient was breathing ambient air. He was somnolent but opened his eyes in response to loud verbal stimuli and intermittently executed simple actions, including wiggling his toes and squeezing the examiner’s hand, after being repeatedly instructed to do so. The patient responded to trapezius pinching by grimacing symmetrically, and he strongly withdrew from painful stimulation of the hands and the right foot. The pupils were equal, round, and reactive to light, constricting from 3 mm to 2 mm. There was mild nuchal rigidity, and Kernig’s sign was present. Examination of the heart revealed persistent tachycardia and was otherwise normal. The incision in the left leg was well approximated and had no surrounding erythema; there was no crepitus on palpation of the soft tissues around the incision. The remainder of the examination was normal. Urinalysis showed 1+ occult blood, 1+ leukocyte esterase, a specific gravity of 1.017, and a pH of 5.0; there were 3 to 5 red cells per high-power field, 10 to 20 white cells per high-power field, and 5 to 10 hyaline casts per low-power field. A serum toxicology screen was negative; a urine toxicology screen was positive for opiates and benzodiazepines. Specimens of urine and blood were obtained for culture.

The patient was transferred to the medicine service for additional evaluation and treatment. On examination 27 hours after the conclusion of surgery, the temperature was 36.7°C, the heart rate 140 beats per minute, the blood pressure 113/86 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. The patient opened his eyes in response to voice and painful stimuli; he did not follow commands. The gaze was slightly deviated to the upper right, and there were occasional roving eye movements. There was mild rigidity of the arms, and the right patellar deep tendon reflex was 3+. The remainder of the examination was unchanged.

Additional studies were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 46-year-old man with myxoid chondrosarcoma of the left femur was evaluated by the internal medicine consult service because he had worsening somnolence 1 day after he underwent proximal femoral replacement surgery.

The patient had been well until 5 weeks before this evaluation, when he slipped and fell onto the pavement during a vacation in Haiti. Left hip pain developed immediately, and he had difficulty getting up after the fall. The patient rested and took ibuprofen, but the pain did not decrease.

Two weeks later, after returning to the United States, the patient went to the emergency department of another hospital and reported that the pain had progressively increased and that he was unable to bear weight on the left leg. He had been previously healthy, was taking no medications, and had no known allergies. He lived in an urban area of New England with his girlfriend, drove a bus, and did not smoke tobacco, drink alcohol, or use illicit drugs. He was born in Haiti and had returned there frequently after moving to New England during childhood. His father had hypertension and diabetes mellitus; there was no known family history of bone or soft-tissue cancer or of venous thromboembolism. On examination, the blood pressure was 154/99 mm Hg, and the other vital signs were normal. There was tenderness over the greater trochanter of the left femur, and the pain increased with rotation of the left hip. Imaging studies were obtained.

Figure 1.

Radiograph of the Left Hip.
Dr. R. Gilberto Gonzalez: A frontal radiograph showed a lytic lesion, measuring 4.8 cm by 3.9 cm, involving the left femoral neck and greater trochanter, with cortical thinning (Figure 1). A region of cortical discontinuity raised concerns about cortical breakthrough or a pathologic fracture.

Dr. Scott: The patient was admitted to the other hospital, and ibuprofen, oxycodone, enoxaparin, amlodipine, docusate, and senna were administered. On the fourth hospital day, the patient was discharged home and advised to follow up with an orthopedic surgeon at this hospital.

The patient was seen in the orthopedic surgery clinic 3 weeks after he had fallen. He reported that the pain had decreased but continued to be present during ambulation and when he slept on his left side. On examination, there was tenderness in response to deep palpation over the greater trochanter of the left femur. A computed tomography (CT)–guided core-needle biopsy of the lytic bone lesion was performed; histopathological examination of the biopsy specimen revealed myxoid chondrosarcoma.

Table 1.

Laboratory Data.
Four weeks after the patient had fallen, he returned to the orthopedic surgery clinic and reported that the pain persisted but had decreased in severity. Laboratory test results are shown in Table 1. A CT scan of the chest, obtained after the administration of intravenous contrast material, showed no evidence of thoracic metastases. Surgical resection of the femoral tumor was scheduled for the following week.

The day before this evaluation, the patient underwent proximal femoral replacement surgery; the left proximal femur was resected, and the hip was reconstructed with the use of a cementless bipolar endoprosthetic implant. The procedure was complicated by a posteriorly oriented crack in the femur that occurred during implantation of the prosthesis.

Figure 2.

Resection Specimen of the Proximal Left Femur.
Dr. Vikram Deshpande: The resection specimen showed myxoid chondrosarcoma (grade 2/3). On macroscopic examination, the tumor measured 3.5 cm by 3.0 cm by 2.5 cm and involved the neck and greater trochanter of the femur (Figure 2A). The tumor infiltrated adjacent cortical and cancellous bone (Figure 2B) and was composed of mononucleate and binucleate cells embedded in abundant myxoid stroma (Figure 2C). On immunohistochemical staining for S100, the tumor cells were diffusely and strongly positive; this nonspecific stain is positive in virtually all cartilaginous cancers, including chondroblastic osteosarcoma. The tumor was accompanied by a fracture callus (Figure 2D). There was no evidence of vascular invasion, and all resected margins were negative for tumor.

Dr. Scott: After completion of the surgery, the patient was transferred to the postanesthesia care unit, where he was initially sleepy but arousable; within 2 hours, he was alert and oriented to person, place, and time, as well as responding appropriately to questions and using patient-controlled analgesia with a morphine infusion pump. Laboratory test results are shown in Table 1. Postoperative radiographs of the left hip and femur showed a nondisplaced fracture of the distal femoral diaphysis extending from the distal tip of the femoral implant to the distal femoral metaphysis. The patient was transferred to the inpatient unit.

The next morning, 12 hours after the conclusion of surgery, the patient reported that his pain was well controlled. Two hours later, he was noted to be drowsier and less interactive. He neither spoke spontaneously nor responded verbally to questions, and he opened his eyes only intermittently when he was spoken to by caregivers. Tachycardia developed; the pulse was 110 beats per minute. Laboratory test results are shown in Table 1. Magnesium sulfate was administered. Sixteen hours after the conclusion of surgery, use of the morphine infusion pump was discontinued. The patient became increasingly somnolent. Two hours later, naloxone was administered; there was a mild, transient increase in eye opening and an increase in heart rate to 137 beats per minute, and hypertension developed, with a blood pressure of 202/107 mm Hg. Metoprolol was administered; the pulse decreased to 106 beats per minute, and the blood pressure to 143/83 mm Hg. The temperature was 38.9°C. Laboratory test results obtained 24 hours after the conclusion of surgery are shown in Table 1.

Dr. Gonzalez: CT of the head, performed without the administration of intravenous contrast material, revealed no evidence of acute intracranial hemorrhage, territorial infarction, or intracranial mass lesion.

Dr. Scott: Medical consultation was requested for persistent somnolence. On evaluation by the consulting physician, the patient was unable to answer any questions. Medications included enoxaparin, amlodipine, a multivitamin, and intravenous fluids. On examination, the temperature was 37.7°C, the pulse 121 beats per minute, the blood pressure 135/89 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation between 95% and 97% while the patient was breathing ambient air. He was somnolent but opened his eyes in response to loud verbal stimuli and intermittently executed simple actions, including wiggling his toes and squeezing the examiner’s hand, after being repeatedly instructed to do so. The patient responded to trapezius pinching by grimacing symmetrically, and he strongly withdrew from painful stimulation of the hands and the right foot. The pupils were equal, round, and reactive to light, constricting from 3 mm to 2 mm. There was mild nuchal rigidity, and Kernig’s sign was present. Examination of the heart revealed persistent tachycardia and was otherwise normal. The incision in the left leg was well approximated and had no surrounding erythema; there was no crepitus on palpation of the soft tissues around the incision. The remainder of the examination was normal. Urinalysis showed 1+ occult blood, 1+ leukocyte esterase, a specific gravity of 1.017, and a pH of 5.0; there were 3 to 5 red cells per high-power field, 10 to 20 white cells per high-power field, and 5 to 10 hyaline casts per low-power field. A serum toxicology screen was negative; a urine toxicology screen was positive for opiates and benzodiazepines. Specimens of urine and blood were obtained for culture.

The patient was transferred to the medicine service for additional evaluation and treatment. On examination 27 hours after the conclusion of surgery, the temperature was 36.7°C, the heart rate 140 beats per minute, the blood pressure 113/86 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. The patient opened his eyes in response to voice and painful stimuli; he did not follow commands. The gaze was slightly deviated to the upper right, and there were occasional roving eye movements. There was mild rigidity of the arms, and the right patellar deep tendon reflex was 3+. The remainder of the examination was unchanged.

Additional studies were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Fat Embolism Syndrome. The patient's symptoms of somnolence, tachycardia, and fever, along with the history of recent orthopedic surgery and the presence of a fracture, suggest a systemic process. Fat embolism syndrome is a known complication of orthopedic procedures, especially those involving the long bones, and can present with neurological symptoms, tachycardia, and fever. The patient's worsening somnolence despite discontinuation of the morphine infusion suggests a non-opioid related cause. The presence of hyaline casts in the urine could also suggest renal involvement in the systemic process. The negative head CT rules out intracranial causes for the patient's somnolence.""
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        ""content"": ""This is a 46-year-old man who presented with worsening somnolence after undergoing proximal femoral replacement surgery for myxoid chondrosarcoma of the left femur. The differential diagnosis for his somnolence includes postoperative delirium, opioid overdose, sepsis, and fat embolism syndrome. Postoperative delirium is common in older patients and those with pre-existing cognitive impairment, neither of which apply to this patient. Opioid overdose is a possibility given the patient's use of a morphine pump for pain control, but his symptoms did not improve significantly after naloxone was administered. Sepsis could cause altered mental status, but the patient's vital signs and laboratory results do not strongly support this diagnosis. Fat embolism syndrome is a rare but serious complication of orthopedic surgeries, especially those involving the long bones. It can cause a triad of symptoms including altered mental status, respiratory distress, and petechial rash. This patient's somnolence and tachycardia could be consistent with this syndrome. \n\nDiagnosis: Fat embolism syndrome.""
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10.1056/NEJMcpc1601838,"Case 22-2016 — A 65-Year-Old Man with Syncope, Dyspnea, and Leg Edema",,Sarcoidosis involving the heart and thoracic and inguinal lymph nodes.,Sarcoidosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 65-year-old man was admitted to this hospital because of syncope, dyspnea, and leg edema.

Table 1.

Laboratory Data.
The patient had been in his usual health until approximately 1 month before admission, when cough occurred. One week later, his legs became swollen and weeping sores developed. Dyspnea on exertion without orthopnea developed and was associated with a weight gain of 7 kg. The patient was seen by his primary care physician at another hospital. On examination, a new cardiac murmur was heard. Laboratory test results are shown in Table 1. Therapy with furosemide and lisinopril was begun, and echocardiography and chest imaging studies were scheduled. Four days before this admission, contrast-enhanced computed tomography (CT) of the chest, performed at another hospital, revealed diffuse bulky lymphadenopathy throughout the mediastinum and both hilar regions, fine reticular lung markings, evidence of previous granulomatous disease in the right middle lobe, an enlarged heart, a thyroid nodule, and ill-defined enlargement of the left adrenal gland.

On the morning of admission, while the patient was boarding a plane for an early flight, light-headedness suddenly developed. Shortly thereafter, he lost consciousness and fell to the aisle on his left side; he had no head trauma. His wife estimated that he was unconscious, with open eyes and jerking movements, for approximately 10 minutes. After regaining consciousness, he reported no chest pain, palpitations, nausea, vomiting, urinary or fecal incontinence, or confusion. He was brought to this hospital by emergency medical services personnel.

The patient had not eaten that morning. He had had hypertension for approximately 3 years. Medications included carvedilol, lisinopril, furosemide, and aspirin. He had no known allergies. He was married and traveled frequently for work. He drank alcohol in moderation and did not use illicit drugs; he had a history of cigarette smoking of 50 pack-years but had stopped 5 years earlier, and he smoked cigars occasionally. His sister had Crohn’s disease, but there was no family history of cardiac disease, arrhythmia, or sudden death.

On examination, the patient was alert and oriented and appeared chronically ill, with bitemporal wasting. The blood pressure was 113/61 mm Hg, the pulse 53 beats per minute, the temperature 36.3°C, the respiratory rate 20 breaths per minute, and the oxygen saturation 94% while he was breathing ambient air. The mucous membranes were dry. Prominent submandibular lymphadenopathy was present. The jugular venous pressure was 15 cm of water, and C-V waves (systolic pulsations) were observed. There were diffuse crackles at the lung bases. The rhythm was slow and regular, with an augmented second heart sound, a midpeaking systolic ejection murmur (grade 3/6) that was loudest at the base, a holosystolic murmur at the left lower sternum (grade 3/6) that increased in magnitude with inspiration, and an apical holosystolic murmur (grade 3/6). A right ventricular heave and a pulsatile liver were present. Prominent inguinal lymphadenopathy was present, along with 3+ pitting edema in both legs; there was no calf tenderness, but multiple healing ulcerations were present on the lower legs. The remainder of the examination was normal. The results of electrocardiography were interpreted as normal, except for evidence of probable left ventricular hypertrophy. The hematocrit, hemoglobin, red-cell indexes, platelet count, and lipid profile were normal, as were blood levels of calcium, phosphorus, total protein, albumin, globulin, aspartate aminotransferase, alanine aminotransferase, uric acid, troponin T, and glycated hemoglobin; other test results are shown in Table 1.

Figure 1.

Imaging Studies of the Chest.
Dr. Suhny Abbara: A chest radiograph showed a prominent right hilum with a lobulated contour, extensive mediastinal and hilar lymphadenopathy, and prominent interstitial markings and reticular opacities with thickening of the fissures, findings suggestive of pulmonary edema (Figure 1). An increased cardiothoracic ratio was indicative of cardiomegaly.

CT of the chest, performed according to the pulmonary-embolism protocol, did not reveal filling defects in the pulmonary arteries, and therefore pulmonary embolism was an unlikely diagnosis (Figure 1). Multiple densely calcified pulmonary nodules were present in both lower lobes and along the right minor fissure; these findings were consistent with previous granulomatous disease. Persistent bulky mediastinal lymphadenopathy was also present. The pulmonary artery was enlarged at 3.5 cm, a finding consistent with pulmonary hypertension possibly due to back pressure resulting from congestion on the left side. The left ventricle and left atrium were enlarged. Coronary atherosclerotic calcifications and mitral annular and aortic calcifications were present, along with flowing anterior osteophytes at multiple levels of the thoracic spine that were consistent with DISH (diffuse idiopathic skeletal hyperostosis); there were no suspicious lytic or blastic lesions.

Although the CT scan was not electrocardiogram-gated, the basal ventricular septum appeared hypertrophied relative to the adjacent myocardium. There was a suggestion of systolic anterior motion of the anterior mitral-valve leaflet in an axial slice that appeared to be acquired during systole (Figure 1).

Dr. Rhee: During the next 3 days, testing for myocardial infarction and a skin test for tuberculosis were negative. Carvedilol therapy was stopped because of bradycardia with pauses longer than 3 seconds, but the patient was noted to have nonsustained ventricular tachycardia on telemetry. Lisinopril was administered once and then switched to captopril. Echocardiography was performed.

Figure 2.

Echocardiographic Images.
Dr. Gary S. Mak: A transthoracic echocardiogram showed asymmetric left ventricular hypertrophy with upper septal predominance (thickness of the septum, 24 mm; thickness of the posterior wall, 16 mm; normal thickness for both, ≤11 mm), a finding consistent with hypertrophic cardiomyopathy. The left ventricle was hyperkinetic, with an ejection fraction of 81% and near obliteration of the midventricular and apical cavity. There was systolic anterior motion of the anterior mitral-valve leaflet, and a left ventricular outflow tract gradient was estimated to be more than 100 mm Hg at rest; both findings are consistent with hypertrophic obstructive cardiomyopathy (Figure 2). Extensive mitral annular calcification encroached on the posterior mitral-valve leaflet, and this resulted in moderate mitral-valve stenosis with a peak transmitral gradient of 21 mm Hg and a mean gradient of 8 mm Hg. There was a flail portion of the posterior mitral-valve leaflet, with severe mitral regurgitation and a dilated left atrium. No obvious valvular vegetations were present. There was severe tricuspid regurgitation and severe pulmonary hypertension, with an estimated right ventricular systolic pressure of 122 mm Hg and interventricular septal compression; the right ventricle was mildly dilated and hypokinetic.

On the fourth day, a transesophageal echocardiogram again showed marked asymmetric left ventricular hypertrophy and systolic anterior motion of the anterior mitral-valve leaflet. The tip of the middle scallop of the posterior mitral-valve leaflet was flail, with an associated chordal remnant. There was severe mitral regurgitation with an eccentrically directed jet, severe tricuspid regurgitation, and right ventricular dilatation and dysfunction. (Figure 2)

Dr. Rhee: On the fifth day, flow cytometry of the peripheral blood showed no evidence of a monoclonal B-cell or unusual T-cell population. Testing for antibodies to human immunodeficiency virus (HIV) and blood cultures were negative.

The next day, a diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 65-year-old man was admitted to this hospital because of syncope, dyspnea, and leg edema.

Table 1.

Laboratory Data.
The patient had been in his usual health until approximately 1 month before admission, when cough occurred. One week later, his legs became swollen and weeping sores developed. Dyspnea on exertion without orthopnea developed and was associated with a weight gain of 7 kg. The patient was seen by his primary care physician at another hospital. On examination, a new cardiac murmur was heard. Laboratory test results are shown in Table 1. Therapy with furosemide and lisinopril was begun, and echocardiography and chest imaging studies were scheduled. Four days before this admission, contrast-enhanced computed tomography (CT) of the chest, performed at another hospital, revealed diffuse bulky lymphadenopathy throughout the mediastinum and both hilar regions, fine reticular lung markings, evidence of previous granulomatous disease in the right middle lobe, an enlarged heart, a thyroid nodule, and ill-defined enlargement of the left adrenal gland.

On the morning of admission, while the patient was boarding a plane for an early flight, light-headedness suddenly developed. Shortly thereafter, he lost consciousness and fell to the aisle on his left side; he had no head trauma. His wife estimated that he was unconscious, with open eyes and jerking movements, for approximately 10 minutes. After regaining consciousness, he reported no chest pain, palpitations, nausea, vomiting, urinary or fecal incontinence, or confusion. He was brought to this hospital by emergency medical services personnel.

The patient had not eaten that morning. He had had hypertension for approximately 3 years. Medications included carvedilol, lisinopril, furosemide, and aspirin. He had no known allergies. He was married and traveled frequently for work. He drank alcohol in moderation and did not use illicit drugs; he had a history of cigarette smoking of 50 pack-years but had stopped 5 years earlier, and he smoked cigars occasionally. His sister had Crohn’s disease, but there was no family history of cardiac disease, arrhythmia, or sudden death.

On examination, the patient was alert and oriented and appeared chronically ill, with bitemporal wasting. The blood pressure was 113/61 mm Hg, the pulse 53 beats per minute, the temperature 36.3°C, the respiratory rate 20 breaths per minute, and the oxygen saturation 94% while he was breathing ambient air. The mucous membranes were dry. Prominent submandibular lymphadenopathy was present. The jugular venous pressure was 15 cm of water, and C-V waves (systolic pulsations) were observed. There were diffuse crackles at the lung bases. The rhythm was slow and regular, with an augmented second heart sound, a midpeaking systolic ejection murmur (grade 3/6) that was loudest at the base, a holosystolic murmur at the left lower sternum (grade 3/6) that increased in magnitude with inspiration, and an apical holosystolic murmur (grade 3/6). A right ventricular heave and a pulsatile liver were present. Prominent inguinal lymphadenopathy was present, along with 3+ pitting edema in both legs; there was no calf tenderness, but multiple healing ulcerations were present on the lower legs. The remainder of the examination was normal. The results of electrocardiography were interpreted as normal, except for evidence of probable left ventricular hypertrophy. The hematocrit, hemoglobin, red-cell indexes, platelet count, and lipid profile were normal, as were blood levels of calcium, phosphorus, total protein, albumin, globulin, aspartate aminotransferase, alanine aminotransferase, uric acid, troponin T, and glycated hemoglobin; other test results are shown in Table 1.

Figure 1.

Imaging Studies of the Chest.
Dr. Suhny Abbara: A chest radiograph showed a prominent right hilum with a lobulated contour, extensive mediastinal and hilar lymphadenopathy, and prominent interstitial markings and reticular opacities with thickening of the fissures, findings suggestive of pulmonary edema (Figure 1). An increased cardiothoracic ratio was indicative of cardiomegaly.

CT of the chest, performed according to the pulmonary-embolism protocol, did not reveal filling defects in the pulmonary arteries, and therefore pulmonary embolism was an unlikely diagnosis (Figure 1). Multiple densely calcified pulmonary nodules were present in both lower lobes and along the right minor fissure; these findings were consistent with previous granulomatous disease. Persistent bulky mediastinal lymphadenopathy was also present. The pulmonary artery was enlarged at 3.5 cm, a finding consistent with pulmonary hypertension possibly due to back pressure resulting from congestion on the left side. The left ventricle and left atrium were enlarged. Coronary atherosclerotic calcifications and mitral annular and aortic calcifications were present, along with flowing anterior osteophytes at multiple levels of the thoracic spine that were consistent with DISH (diffuse idiopathic skeletal hyperostosis); there were no suspicious lytic or blastic lesions.

Although the CT scan was not electrocardiogram-gated, the basal ventricular septum appeared hypertrophied relative to the adjacent myocardium. There was a suggestion of systolic anterior motion of the anterior mitral-valve leaflet in an axial slice that appeared to be acquired during systole (Figure 1).

Dr. Rhee: During the next 3 days, testing for myocardial infarction and a skin test for tuberculosis were negative. Carvedilol therapy was stopped because of bradycardia with pauses longer than 3 seconds, but the patient was noted to have nonsustained ventricular tachycardia on telemetry. Lisinopril was administered once and then switched to captopril. Echocardiography was performed.

Figure 2.

Echocardiographic Images.
Dr. Gary S. Mak: A transthoracic echocardiogram showed asymmetric left ventricular hypertrophy with upper septal predominance (thickness of the septum, 24 mm; thickness of the posterior wall, 16 mm; normal thickness for both, ≤11 mm), a finding consistent with hypertrophic cardiomyopathy. The left ventricle was hyperkinetic, with an ejection fraction of 81% and near obliteration of the midventricular and apical cavity. There was systolic anterior motion of the anterior mitral-valve leaflet, and a left ventricular outflow tract gradient was estimated to be more than 100 mm Hg at rest; both findings are consistent with hypertrophic obstructive cardiomyopathy (Figure 2). Extensive mitral annular calcification encroached on the posterior mitral-valve leaflet, and this resulted in moderate mitral-valve stenosis with a peak transmitral gradient of 21 mm Hg and a mean gradient of 8 mm Hg. There was a flail portion of the posterior mitral-valve leaflet, with severe mitral regurgitation and a dilated left atrium. No obvious valvular vegetations were present. There was severe tricuspid regurgitation and severe pulmonary hypertension, with an estimated right ventricular systolic pressure of 122 mm Hg and interventricular septal compression; the right ventricle was mildly dilated and hypokinetic.

On the fourth day, a transesophageal echocardiogram again showed marked asymmetric left ventricular hypertrophy and systolic anterior motion of the anterior mitral-valve leaflet. The tip of the middle scallop of the posterior mitral-valve leaflet was flail, with an associated chordal remnant. There was severe mitral regurgitation with an eccentrically directed jet, severe tricuspid regurgitation, and right ventricular dilatation and dysfunction. (Figure 2)

Dr. Rhee: On the fifth day, flow cytometry of the peripheral blood showed no evidence of a monoclonal B-cell or unusual T-cell population. Testing for antibodies to human immunodeficiency virus (HIV) and blood cultures were negative.

The next day, a diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of syncope, dyspnea, and leg edema, along with the findings of a new cardiac murmur, prominent submandibular lymphadenopathy, and prominent inguinal lymphadenopathy, suggest a cardiac issue. The echocardiogram showed asymmetric left ventricular hypertrophy with upper septal predominance, a hyperkinetic left ventricle, systolic anterior motion of the anterior mitral-valve leaflet, and a left ventricular outflow tract gradient estimated to be more than 100 mm Hg at rest. These findings are consistent with hypertrophic obstructive cardiomyopathy. The patient also had moderate mitral-valve stenosis, severe mitral regurgitation, severe tricuspid regurgitation, and severe pulmonary hypertension. These findings further support the diagnosis of hypertrophic obstructive cardiomyopathy.""
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        ""content"": ""The patient's symptoms of syncope, dyspnea, and leg edema, along with the physical examination findings of a new cardiac murmur, jugular venous pressure of 15 cm of water, and a right ventricular heave, suggest a cardiac origin for his symptoms. The echocardiogram findings of asymmetric left ventricular hypertrophy, systolic anterior motion of the anterior mitral-valve leaflet, and a left ventricular outflow tract gradient estimated to be more than 100 mm Hg at rest are consistent with hypertrophic obstructive cardiomyopathy. The presence of severe mitral regurgitation and a dilated left atrium further support this diagnosis. The patient's history of hypertension and the finding of probable left ventricular hypertrophy on electrocardiography also support a diagnosis of hypertrophic cardiomyopathy. \n\nDiagnosis: Hypertrophic Obstructive Cardiomyopathy""
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        ""content"": ""The patient is a 65-year-old man presenting with syncope, dyspnea, and leg edema. He also has a history of hypertension and a significant smoking history. His symptoms and physical examination findings suggest heart failure, which is supported by the presence of a new cardiac murmur, jugular venous distension, a pulsatile liver, and pitting edema in both legs. The differential diagnosis includes ischemic heart disease, valvular heart disease, hypertrophic cardiomyopathy, and constrictive pericarditis. The patient's history of hypertension and smoking makes ischemic heart disease a possibility. However, the absence of chest pain and the normal troponin T level make this less likely. Valvular heart disease could also cause his symptoms, but the presence of asymmetric left ventricular hypertrophy with upper septal predominance and a left ventricular outflow tract gradient of more than 100 mm Hg at rest on echocardiography is more suggestive of hypertrophic cardiomyopathy. Constrictive pericarditis could also present with similar symptoms, but this is less likely given the absence of pericardial calcification on imaging. The presence of systolic anterior motion of the anterior mitral-valve leaflet and a left ventricular outflow tract gradient of more than 100 mm Hg at rest on echocardiography confirms the diagnosis of hypertrophic cardiomyopathy. \n\nDiagnosis: Hypertrophic cardiomyopathy.""
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10.1056/NEJMcpc1600838,Case 21-2016 — A 32-Year-Old Man in an Unresponsive State,,Fulminant liver failure associated with hepatitis B virus infection.,"Fulminant liver failure due to acute hepatitis B virus infection, with possible hepatitis D virus coinfection or superinfection.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 32-year-old incarcerated man was admitted to this hospital after being found in an unresponsive state in his jail cell.

Two days before this admission, the patient had had nausea and vomiting. Acetaminophen, at a dose of 650 mg up to three times daily as needed, was prescribed, in addition to a preexisting prescription for acetaminophen at a dose of 325 mg twice daily. Earlier during the day of admission, the patient was reported to be acting strangely; later, he was found in an unresponsive state on the floor of his cell. Emergency medical services personnel were called to the jail, where they found the patient in an unresponsive state, in a decerebrate posture, and incontinent of urine. The blood glucose level, obtained by finger-stick testing, was less than 10 mg per deciliter (<0.6 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). The patient was transported by ambulance to the emergency department of this hospital.

Table 1.

Laboratory Data.
The available medical history was limited. The patient had a history of substance-use disorder (including the use of alcohol, opiates, and cocaine), traumatic brain injuries, seizures, anemia, and a psychotic disorder for which the diagnosis of paranoid schizophrenia had been considered. Six years before the current presentation, tests for human immunodeficiency virus (HIV) antibodies, hepatitis C virus (HCV) antibodies, and hepatitis B virus (HBV) surface antigen were negative, and a test for HBV surface antibodies was positive. The patient had been assaulted several times during the 14 months before this admission; the assaults had resulted in a subdural hematoma, orbital and nasal fractures, and jaw fractures. Eight months before the current admission, he had been admitted to this hospital for altered behavior. On evaluation, he had had an unremarkable computed tomographic (CT) scan of the head, hyperammonemia that was thought to be related to alcoholism, and an echogenic liver on ultrasonography that was thought to represent a combination of fatty infiltration and fibrosis; his mental status improved with the administration of lactulose. Six weeks before the current admission, the patient had been evaluated at this hospital because of facial injuries. CT scans of the face, brain, and neck were unremarkable; laboratory test results are shown in Table 1. Medications included lactulose, thiamine, sertraline, oxycodone, ibuprofen, and acetaminophen. Details of the patient’s family history were unavailable. The patient had been homeless. He had smoked one pack of cigarettes daily for the past 15 years, had drunk several pints of vodka daily before incarceration, and had previously reported using intranasal cocaine and heroin.

On examination in the emergency department, the patient was unresponsive and had grunting respirations. The temperature was 36.9°C, the pulse 112 beats per minute, and the blood pressure 170/119 mm Hg. The skin was jaundiced and the sclerae icteric. The pupils were equal in size; the right pupil reacted to light more slowly than the left pupil. There was diffuse hypertonicity, extensor posturing of the arms, myoclonic jerking movements of the legs, and clonus. A systolic flow murmur was heard on auscultation, and the abdomen was mildly distended.

Intravenous dextrose and lorazepam were administered on arrival, and endotracheal intubation was performed. A urine toxicology screen was negative. A complete serum toxicology screen revealed no detectable acetaminophen; metabolites of chlordiazepoxide and diazepam were present. Other laboratory test results are shown in Table 1. Intravenous thiamine, propofol, N-acetylcysteine, hydrocortisone, vitamin K, and fresh-frozen plasma were administered. Lactulose was administered through an orogastric tube. Imaging studies were performed.

Figure 1.

Chest Radiograph and Abdominal Ultrasound Image.
Dr. Pamela W. Schaefer: A chest radiograph showed discoid atelectasis at the left lung base (Figure 1A). An abdominal ultrasound image showed a thick, hypoechoic gallbladder wall (Figure 1B), a finding that can be associated with hepatitis. A CT scan of the head, obtained without the administration of contrast material, showed effacement of sulci, a finding consistent with mild brain swelling. There was preservation of gray-white matter differentiation and no evidence of acute ischemia or acute intracranial hemorrhage.

Dr. Vanderhoek: The patient was admitted to the intensive care unit for additional evaluation and treatment.

Figure 2.

MRI of the Head.
Dr. Schaefer: Magnetic resonance imaging of the head, performed 22 hours later, revealed swelling of the cortex and thalami; increased signal was seen on fluid-attenuated inversion recovery images. There was also increased signal in the cortex and thalami on diffusion-weighted images and corresponding decreased signal on apparent diffusion coefficient maps; these findings are consistent with decreased diffusion, which signifies that the edema is cytotoxic (Figure 2).

Dr. Vanderhoek: Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 32-year-old incarcerated man was admitted to this hospital after being found in an unresponsive state in his jail cell.

Two days before this admission, the patient had had nausea and vomiting. Acetaminophen, at a dose of 650 mg up to three times daily as needed, was prescribed, in addition to a preexisting prescription for acetaminophen at a dose of 325 mg twice daily. Earlier during the day of admission, the patient was reported to be acting strangely; later, he was found in an unresponsive state on the floor of his cell. Emergency medical services personnel were called to the jail, where they found the patient in an unresponsive state, in a decerebrate posture, and incontinent of urine. The blood glucose level, obtained by finger-stick testing, was less than 10 mg per deciliter (<0.6 mmol per liter; reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per liter]). The patient was transported by ambulance to the emergency department of this hospital.

Table 1.

Laboratory Data.
The available medical history was limited. The patient had a history of substance-use disorder (including the use of alcohol, opiates, and cocaine), traumatic brain injuries, seizures, anemia, and a psychotic disorder for which the diagnosis of paranoid schizophrenia had been considered. Six years before the current presentation, tests for human immunodeficiency virus (HIV) antibodies, hepatitis C virus (HCV) antibodies, and hepatitis B virus (HBV) surface antigen were negative, and a test for HBV surface antibodies was positive. The patient had been assaulted several times during the 14 months before this admission; the assaults had resulted in a subdural hematoma, orbital and nasal fractures, and jaw fractures. Eight months before the current admission, he had been admitted to this hospital for altered behavior. On evaluation, he had had an unremarkable computed tomographic (CT) scan of the head, hyperammonemia that was thought to be related to alcoholism, and an echogenic liver on ultrasonography that was thought to represent a combination of fatty infiltration and fibrosis; his mental status improved with the administration of lactulose. Six weeks before the current admission, the patient had been evaluated at this hospital because of facial injuries. CT scans of the face, brain, and neck were unremarkable; laboratory test results are shown in Table 1. Medications included lactulose, thiamine, sertraline, oxycodone, ibuprofen, and acetaminophen. Details of the patient’s family history were unavailable. The patient had been homeless. He had smoked one pack of cigarettes daily for the past 15 years, had drunk several pints of vodka daily before incarceration, and had previously reported using intranasal cocaine and heroin.

On examination in the emergency department, the patient was unresponsive and had grunting respirations. The temperature was 36.9°C, the pulse 112 beats per minute, and the blood pressure 170/119 mm Hg. The skin was jaundiced and the sclerae icteric. The pupils were equal in size; the right pupil reacted to light more slowly than the left pupil. There was diffuse hypertonicity, extensor posturing of the arms, myoclonic jerking movements of the legs, and clonus. A systolic flow murmur was heard on auscultation, and the abdomen was mildly distended.

Intravenous dextrose and lorazepam were administered on arrival, and endotracheal intubation was performed. A urine toxicology screen was negative. A complete serum toxicology screen revealed no detectable acetaminophen; metabolites of chlordiazepoxide and diazepam were present. Other laboratory test results are shown in Table 1. Intravenous thiamine, propofol, N-acetylcysteine, hydrocortisone, vitamin K, and fresh-frozen plasma were administered. Lactulose was administered through an orogastric tube. Imaging studies were performed.

Figure 1.

Chest Radiograph and Abdominal Ultrasound Image.
Dr. Pamela W. Schaefer: A chest radiograph showed discoid atelectasis at the left lung base (Figure 1A). An abdominal ultrasound image showed a thick, hypoechoic gallbladder wall (Figure 1B), a finding that can be associated with hepatitis. A CT scan of the head, obtained without the administration of contrast material, showed effacement of sulci, a finding consistent with mild brain swelling. There was preservation of gray-white matter differentiation and no evidence of acute ischemia or acute intracranial hemorrhage.

Dr. Vanderhoek: The patient was admitted to the intensive care unit for additional evaluation and treatment.

Figure 2.

MRI of the Head.
Dr. Schaefer: Magnetic resonance imaging of the head, performed 22 hours later, revealed swelling of the cortex and thalami; increased signal was seen on fluid-attenuated inversion recovery images. There was also increased signal in the cortex and thalami on diffusion-weighted images and corresponding decreased signal on apparent diffusion coefficient maps; these findings are consistent with decreased diffusion, which signifies that the edema is cytotoxic (Figure 2).

Dr. Vanderhoek: Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Hypoglycemic brain injury. The patient was found in an unresponsive state with a blood glucose level of less than 10 mg per deciliter. The MRI of the head revealed swelling of the cortex and thalami, consistent with cytotoxic edema, which can be caused by severe hypoglycemia. The patient's history of substance use disorder and the presence of acetaminophen in his prescribed medications suggest the possibility of an overdose leading to hypoglycemia.""
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        ""content"": ""The patient's symptoms of unresponsiveness, decerebrate posture, incontinence, and low blood glucose level suggest a severe metabolic or neurological disorder. The patient's history of substance abuse, including alcohol, opiates, and cocaine, could contribute to a variety of conditions, including withdrawal syndromes, toxic effects, or metabolic derangements. The patient's history of traumatic brain injuries could also contribute to his current state, but the recent imaging of the head was unremarkable. The patient's history of anemia and psychotic disorder are less likely to be directly related to his current presentation. The patient's jaundiced skin and sclerae suggest liver disease, which could be due to alcohol abuse, hepatitis, or other causes. The patient's hypertonicity, extensor posturing, myoclonic jerking, and clonus suggest a severe neurological disorder. The patient's negative urine toxicology screen and serum toxicology screen suggest that his current state is not due to a recent ingestion of a toxic substance. The patient's MRI findings of swelling of the cortex and thalami and decreased diffusion suggest cytotoxic edema, which could be due to a variety of causes, including ischemia, infection, or toxic effects. Given the patient's history of substance abuse, his liver disease, and his neurological findings, the most likely diagnosis is hepatic encephalopathy.\n\nDiagnosis: Hepatic encephalopathy.""
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        ""content"": ""The patient is a 32-year-old man with a history of substance abuse, traumatic brain injuries, seizures, anemia, and a psychotic disorder. He was found unresponsive in his jail cell with a blood glucose level of less than 10 mg per deciliter. The differential diagnosis for this patient includes hypoglycemia, drug overdose, withdrawal from alcohol or drugs, traumatic brain injury, and liver disease. The patient's blood glucose level was extremely low, which could cause the unresponsiveness. However, the patient's history of substance abuse and the fact that he was found in a decerebrate posture and incontinent of urine suggest a possible drug overdose or withdrawal. The patient's history of traumatic brain injuries and the fact that he had been assaulted several times in the past year also raise the possibility of a new traumatic brain injury. Finally, the patient's history of anemia and a psychotic disorder, as well as the fact that he had an echogenic liver on ultrasonography eight months before the current admission, suggest the possibility of liver disease. The patient's jaundiced skin and icteric sclerae on examination in the emergency department further support this possibility. The patient's MRI showed swelling of the cortex and thalami, which is consistent with decreased diffusion and suggests cytotoxic edema. This could be caused by liver disease, as the liver is responsible for detoxifying harmful substances in the blood. If the liver is not functioning properly, these substances can build up in the blood and cause damage to the brain. \n\nDiagnosis: Acute liver failure leading to hepatic encephalopathy.""
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10.1056/NEJMcpc1600611,"Case 20-2016 — A 50-Year-Old Man with Cloudy Vision, Hearing Loss, and Unsteadiness",,"Secondary syphilis with neurologic, ocular, and otologic involvement.",Secondary syphilis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 50-year-old man with psoriatic arthritis and human immunodeficiency virus (HIV) infection was seen at the Massachusetts Eye and Ear Infirmary because of cloudy vision.

The patient had been in his usual state of health until 3 days before this evaluation, when cloudy vision in both eyes developed gradually over the course of the day. Three days later, he sought medical attention at the emergency department of the Massachusetts Eye and Ear Infirmary. On arrival, he reported fatigue. He also reported that the rash, joint pain, and stiffness associated with his psoriatic arthritis had recently worsened.

Sixteen years before this evaluation, the patient had had laser surgery for a retinal tear in the left eye. Ten months before this evaluation, he had had an episode of Pneumocystis jirovecii pneumonia that led to an evaluation for and diagnosis of HIV infection, and he had begun taking antiretroviral medications 2 months before this evaluation. Six weeks before this evaluation, he had been admitted to another hospital because of hypotension, hyponatremia, pancytopenia, and acute kidney injury; the serum alkaline phosphatase level was elevated, the CD4 count and blood cortisol level were low, and blood cultures had no growth. Adrenal insufficiency, disseminated infection with Mycobacterium avium–intracellulare, and the immune reconstitution inflammatory syndrome were suspected. Antiretroviral medications were stopped, and azithromycin, rifabutin, ethambutol, hydrocortisone, and fludrocortisone were administered, as was trimethoprim–sulfamethoxazole three times weekly. Two weeks before this evaluation, emtricitabine, tenofovir, ritonavir, and darunavir were again initiated. The patient had no known allergies. He lived with his husband, did not smoke tobacco or use illicit drugs, and drank alcohol socially.

On examination, the patient was alert and oriented to person, place, and time. The pulse was 91 beats per minute, the blood pressure 121/77 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. Ophthalmologic examination revealed visual acuity of 20/25 in the right eye and 20/30 in the left eye. The pupils were equally round and reactive to light; there was no relative afferent pupillary defect. The visual fields were full in response to confrontation. Examination of extraocular motility revealed full motility in both eyes. The intraocular pressure was 8 mm Hg in the right eye and 7 mm Hg in the left eye. Slit-lamp examination revealed 1+ injection of the conjunctivae, 2+ cells in the right anterior chamber, 4+ cells in the left anterior chamber, no hypopyon, and diffuse fine and large keratic precipitates on the corneas. Indirect ophthalmoscopy revealed 1+ vitreous cells and normal fundi with cup-to-disk ratios of 0.3 bilaterally.

Table 1.

Laboratory Data.
The platelet count, red-cell indexes, anion gap, and results of renal-function tests were normal, as were blood levels of calcium, glucose, uric acid, total protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin. Other laboratory test results are shown in Table 1. The patient was discharged home with topical ophthalmic prednisolone for presumed psoriatic arthritis–associated iritis.

Five days later, the patient was seen at a follow-up visit, and cloudy vision persisted. The patient also reported that decreased hearing and difficulty balancing had developed synchronously with his ocular symptoms. On examination, visual acuity was 20/30 in the right eye and 20/40 in the left eye. Anisocoria was present in both bright and dim lighting conditions; there was a subtle relative afferent pupillary defect in the left eye. The intraocular pressure was 12 mm Hg in the right eye and 11 mm Hg in the left eye. Slit-lamp examination revealed trace injection of the superior conjunctiva of the left eye, 1+ cells in the anterior chambers, posterior synechiae at the 3 o’clock position of the right eye, extensive posterior synechiae of the left eye, and diffuse fine and large keratic precipitates on the corneas that were more abundant in the left eye than in the right eye. Indirect ophthalmoscopy revealed normal fundi, 1+ vitreous cells in the right eye, and 2+ vitreous cells in the left eye.

Figure 1.

Photograph of the Hands.
A diffuse rash characterized by erythematous plaques and overlying white scale was present and involved the face, abdomen, back, arms, legs, palms, and soles (Figure 1). Results of serologic testing that had been performed during the emergency department visit 5 days earlier were received. The angiotensin-converting–enzyme level was 80 U per liter (reference range, 9 to 67), and the lysozyme level 14.9 _g per milliliter (reference range, 7.0 to 15.0). Antinuclear antibodies were absent, HLA-B27 was present, and a screening test for antibodies to Borrelia burgdorferi was positive. Topical ophthalmic prednisolone was continued, and ophthalmic cyclopentolate was prescribed for the presumptive diagnosis of psoriatic arthritis–associated iritis.

Eleven days after the initial presentation, the patient was seen by an otolaryngologist because his hearing loss and unsteadiness had worsened. An audiogram revealed moderate sensorineural hearing loss that was worse on the left side than on the right. Later that day, the patient returned to the Massachusetts Eye and Ear Infirmary because of worsened visual cloudiness and a new floater in the right eye. On examination, the visual acuity was 20/100 in the right eye and 20/375 in the left eye. Anisocoria was present. There was no relative afferent pupillary defect. The intraocular pressure was 8 mm Hg in both eyes. Slit-lamp examination revealed extensive keratic precipitates on the corneas, 4+ cells in the right anterior chamber, and 3+ cells in the left anterior chamber. Indirect ophthalmoscopy revealed 3+ vitreous cells in the right eye with 2+ vitreous haze and 4+ vitreous cells in the left eye with 4+ vitreous haze. There were many small, yellow bilateral inferotemporal preretinal infiltrates.

Figure 2.

Imaging Studies of the Right Eye.
Optical coherence tomography revealed shadowing from vitreous opacities and a normal foveal contour in the right eye; in the left eye, there was a poor view of the retina, and an image of the macula could not be obtained. Fluorescein angiography revealed a hazy view of the right eye with staining of the peripheral retina, particularly inferiorly, as well as a very hazy view of the left eye with some leakage and staining of the retina nasally and temporally (Figure 2). A repeat test for B. burgdorferi antibodies was negative.

A diagnostic test result was received.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 50-year-old man with psoriatic arthritis and human immunodeficiency virus (HIV) infection was seen at the Massachusetts Eye and Ear Infirmary because of cloudy vision.

The patient had been in his usual state of health until 3 days before this evaluation, when cloudy vision in both eyes developed gradually over the course of the day. Three days later, he sought medical attention at the emergency department of the Massachusetts Eye and Ear Infirmary. On arrival, he reported fatigue. He also reported that the rash, joint pain, and stiffness associated with his psoriatic arthritis had recently worsened.

Sixteen years before this evaluation, the patient had had laser surgery for a retinal tear in the left eye. Ten months before this evaluation, he had had an episode of Pneumocystis jirovecii pneumonia that led to an evaluation for and diagnosis of HIV infection, and he had begun taking antiretroviral medications 2 months before this evaluation. Six weeks before this evaluation, he had been admitted to another hospital because of hypotension, hyponatremia, pancytopenia, and acute kidney injury; the serum alkaline phosphatase level was elevated, the CD4 count and blood cortisol level were low, and blood cultures had no growth. Adrenal insufficiency, disseminated infection with Mycobacterium avium–intracellulare, and the immune reconstitution inflammatory syndrome were suspected. Antiretroviral medications were stopped, and azithromycin, rifabutin, ethambutol, hydrocortisone, and fludrocortisone were administered, as was trimethoprim–sulfamethoxazole three times weekly. Two weeks before this evaluation, emtricitabine, tenofovir, ritonavir, and darunavir were again initiated. The patient had no known allergies. He lived with his husband, did not smoke tobacco or use illicit drugs, and drank alcohol socially.

On examination, the patient was alert and oriented to person, place, and time. The pulse was 91 beats per minute, the blood pressure 121/77 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. Ophthalmologic examination revealed visual acuity of 20/25 in the right eye and 20/30 in the left eye. The pupils were equally round and reactive to light; there was no relative afferent pupillary defect. The visual fields were full in response to confrontation. Examination of extraocular motility revealed full motility in both eyes. The intraocular pressure was 8 mm Hg in the right eye and 7 mm Hg in the left eye. Slit-lamp examination revealed 1+ injection of the conjunctivae, 2+ cells in the right anterior chamber, 4+ cells in the left anterior chamber, no hypopyon, and diffuse fine and large keratic precipitates on the corneas. Indirect ophthalmoscopy revealed 1+ vitreous cells and normal fundi with cup-to-disk ratios of 0.3 bilaterally.

Table 1.

Laboratory Data.
The platelet count, red-cell indexes, anion gap, and results of renal-function tests were normal, as were blood levels of calcium, glucose, uric acid, total protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin. Other laboratory test results are shown in Table 1. The patient was discharged home with topical ophthalmic prednisolone for presumed psoriatic arthritis–associated iritis.

Five days later, the patient was seen at a follow-up visit, and cloudy vision persisted. The patient also reported that decreased hearing and difficulty balancing had developed synchronously with his ocular symptoms. On examination, visual acuity was 20/30 in the right eye and 20/40 in the left eye. Anisocoria was present in both bright and dim lighting conditions; there was a subtle relative afferent pupillary defect in the left eye. The intraocular pressure was 12 mm Hg in the right eye and 11 mm Hg in the left eye. Slit-lamp examination revealed trace injection of the superior conjunctiva of the left eye, 1+ cells in the anterior chambers, posterior synechiae at the 3 o’clock position of the right eye, extensive posterior synechiae of the left eye, and diffuse fine and large keratic precipitates on the corneas that were more abundant in the left eye than in the right eye. Indirect ophthalmoscopy revealed normal fundi, 1+ vitreous cells in the right eye, and 2+ vitreous cells in the left eye.

Figure 1.

Photograph of the Hands.
A diffuse rash characterized by erythematous plaques and overlying white scale was present and involved the face, abdomen, back, arms, legs, palms, and soles (Figure 1). Results of serologic testing that had been performed during the emergency department visit 5 days earlier were received. The angiotensin-converting–enzyme level was 80 U per liter (reference range, 9 to 67), and the lysozyme level 14.9 _g per milliliter (reference range, 7.0 to 15.0). Antinuclear antibodies were absent, HLA-B27 was present, and a screening test for antibodies to Borrelia burgdorferi was positive. Topical ophthalmic prednisolone was continued, and ophthalmic cyclopentolate was prescribed for the presumptive diagnosis of psoriatic arthritis–associated iritis.

Eleven days after the initial presentation, the patient was seen by an otolaryngologist because his hearing loss and unsteadiness had worsened. An audiogram revealed moderate sensorineural hearing loss that was worse on the left side than on the right. Later that day, the patient returned to the Massachusetts Eye and Ear Infirmary because of worsened visual cloudiness and a new floater in the right eye. On examination, the visual acuity was 20/100 in the right eye and 20/375 in the left eye. Anisocoria was present. There was no relative afferent pupillary defect. The intraocular pressure was 8 mm Hg in both eyes. Slit-lamp examination revealed extensive keratic precipitates on the corneas, 4+ cells in the right anterior chamber, and 3+ cells in the left anterior chamber. Indirect ophthalmoscopy revealed 3+ vitreous cells in the right eye with 2+ vitreous haze and 4+ vitreous cells in the left eye with 4+ vitreous haze. There were many small, yellow bilateral inferotemporal preretinal infiltrates.

Figure 2.

Imaging Studies of the Right Eye.
Optical coherence tomography revealed shadowing from vitreous opacities and a normal foveal contour in the right eye; in the left eye, there was a poor view of the retina, and an image of the macula could not be obtained. Fluorescein angiography revealed a hazy view of the right eye with staining of the peripheral retina, particularly inferiorly, as well as a very hazy view of the left eye with some leakage and staining of the retina nasally and temporally (Figure 2). A repeat test for B. burgdorferi antibodies was negative.

A diagnostic test result was received.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Syphilis. The patient's symptoms of cloudy vision, rash, joint pain, and stiffness, along with the worsening of his psoriatic arthritis, suggest an inflammatory or infectious process. The patient's history of HIV infection and recent diagnosis of Mycobacterium avium\u2013intracellulare infection suggest a compromised immune system, making him more susceptible to other infections. The presence of anisocoria, keratic precipitates, and vitreous cells on ophthalmologic examination suggest an ocular inflammatory process, which could be caused by an infectious agent. The patient's rash, which involves the face, abdomen, back, arms, legs, palms, and soles, is consistent with the rash seen in secondary syphilis. The patient's worsening sensorineural hearing loss and unsteadiness could be due to neurosyphilis. The negative test for B. burgdorferi antibodies rules out Lyme disease as a cause of the patient's symptoms. The patient's sexual history is not mentioned, but syphilis is a sexually transmitted infection, and the patient's HIV infection suggests that he may have been exposed to other sexually transmitted infections.""
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        ""content"": ""The patient has a history of HIV and psoriatic arthritis. He presents with cloudy vision, fatigue, and worsening rash, joint pain, and stiffness. His ophthalmologic examination reveals inflammation in the anterior chamber of the eye, known as iritis or anterior uveitis. This condition can be associated with autoimmune diseases, infections, and trauma. Given the patient's history of psoriatic arthritis, an autoimmune disease, the initial assumption is that the iritis is associated with this condition. However, the patient's vision and balance continue to worsen, and he develops sensorineural hearing loss. These symptoms, along with the presence of small, yellow preretinal infiltrates in the eye, suggest a systemic inflammatory condition. The patient's history of HIV infection makes him susceptible to opportunistic infections, but his negative blood cultures and the lack of improvement with antibiotics suggest that an infection is not the primary cause of his symptoms. The elevated angiotensin-converting enzyme level and the presence of HLA-B27, a genetic marker associated with certain autoimmune diseases, support the diagnosis of an autoimmune condition. The combination of uveitis, sensorineural hearing loss, and balance issues is characteristic of Vogt-Koyanagi-Harada disease, an autoimmune disease that affects melanocytes, which are present in the eyes, inner ear, skin, and meninges.\n\nDiagnosis: Vogt-Koyanagi-Harada disease.""
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        ""content"": ""Syphilis\n\nThis patient presents with cloudy vision, rash, joint pain, and stiffness. He also has a history of HIV infection and psoriatic arthritis. The differential diagnosis for this patient includes psoriatic arthritis-associated iritis, syphilis, Lyme disease, and other infectious causes of uveitis. The patient's worsening rash, joint pain, and stiffness could be due to a flare of his psoriatic arthritis, but this would not explain his visual symptoms. Lyme disease could cause these symptoms, but the patient's screening test for antibodies to Borrelia burgdorferi was positive initially and then negative on repeat, making this diagnosis less likely. The patient's HIV infection puts him at risk for various opportunistic infections, but his CD4 count is not severely low and he is on antiretroviral therapy. The patient's visual symptoms, rash, and joint pain, along with his history of HIV infection, are highly suggestive of syphilis. Syphilis can cause uveitis and is known as the \""great imitator\"" because it can cause a wide range of symptoms. The patient's rash, which involves the palms and soles, is also characteristic of secondary syphilis. Given the patient's symptoms and history, syphilis is the most likely diagnosis.""
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 10.1056/NEJMcpc1512457,Case 19-2016 — A 65-Year-Old Man with End-Stage Renal Disease and a Pruritic Rash,,Adult T-cell leukemia–lymphoma.,Adult T-cell leukemia–lymphoma.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 65-year-old man with end-stage renal disease was seen in the emergency department of this hospital because of a leg injury and a diffuse pruritic rash.

The patient was in poor health, with end-stage renal disease that required hemodialysis. Two years before the current presentation, pathological examination of a renal-biopsy specimen revealed advanced global glomerulosclerosis with tubular atrophy and interstitial fibrosis, as well as collapsing focal and segmental glomerulosclerosis, findings that were superimposed on advanced membranous nephropathy.

Table 1.

Laboratory Data.
Six months before the current presentation, evaluation at this hospital revealed severe hypertension, hyperkalemia, and azotemia. Hemodialysis was initiated. Three months before the current presentation, initial evaluation for renal transplantation revealed that the patient had received a diagnosis of secondary syphilis 11 years earlier (on the basis of a positive rapid plasma reagin [RPR] test at a 1:2 dilution and a negative cerebrospinal fluid analysis), for which he received three doses of intramuscular penicillin G benzathine at 1-week intervals; a follow-up RPR test that was performed 4 years before the current presentation was nonreactive. Results of serologic testing for hepatitis A virus and hepatitis B virus were consistent with protective immunity. Testing was negative for hepatitis C virus and human immunodeficiency virus (HIV) types 1 and 2 and positive for human T-lymphotropic virus type 1 (HTLV-1); other test results are shown in Table 1.

Shortly thereafter, the patient noted a rash on his forearms that he thought was associated with oxycodone, which he was taking for pain associated with the placement of a new hemodialysis fistula. Three weeks before the current presentation, as part of the pretransplantation evaluation, he was seen by an infectious-disease specialist in the outpatient clinic of this hospital. He reported no recent fevers, chills, or weight loss and no history of eczema, psoriasis, or a similar rash. On examination, the vital signs were normal. Nummular (circular or oval), scaly, plaquelike lesions were present on the trunk, arms, and legs, and there was bilateral inguinal lymphadenopathy; the remainder of the examination was normal. An RPR test was reactive at a 1:1 dilution. Renal transplantation was postponed, pending evaluation by a dermatologist. During the next 3 weeks, the rash became pruritic and progressed, with more extensive involvement of the torso, arms, and legs. Three days before the current presentation, while awaiting dermatologic consultation, the patient fell and injured his right leg and left shoulder. Three days later, he came to the emergency department of this hospital because of pain with weight bearing and leg swelling.

The patient had hypertension, a bicuspid aortic valve, and an ascending and aortic-root aneurysm; 13 years before this presentation, he had had a positive tuberculin skin test with a negative chest radiograph. He had had unintentional weight loss of 12 kg during the previous 2 years. His medications were oxycodone with acetaminophen, calcitriol, calcium acetate, clonidine, diltiazem, labetalol, atorvastatin, sertraline, ergocalciferol, a multivitamin, and, during dialysis, epoetin alfa. He also topically applied an emollient and a 5% lidocaine patch. He had no known drug or food allergies. He was born in Haiti and had moved to the United States 30 years earlier. He was married and retired from work in a medical facility. He had smoked cigarettes for 15 years before stopping 20 years earlier and did not drink alcohol or use illicit drugs. His parents had died in their 80s, and his siblings and children were well. There was no family history of skin cancer or other dermatologic diseases.

On examination, the vital signs were normal. The right leg was erythematous, with increased warmth and tense nonpitting edema on the medial proximal leg, point tenderness on the medial leg below the knee, 2+ dorsalis pedis pulses, and no findings suggestive of a thrombosed vein. A diffuse rash was present on the torso, arms, and legs. The remainder of the examination was normal. Blood levels of calcium, phosphorus, and magnesium were normal; other test results are shown in Table 1. A radiograph of the knee and leg showed no evidence of a fracture or dislocation. Noninvasive vascular studies of the legs revealed no evidence of deep or superficial venous thrombosis. Vancomycin was administered intravenously.

Figure 1.

Clinical Photographs.
The patient was admitted to the observation unit of this hospital. On examination by a dermatologist, the skin type was Fitzpatrick type VI. Large, brown, thin, flat-topped papules were widespread, and many coalesced into polygonal plaques. There was a powdery and occasionally thick scale on the neck, arms, axillae, wrists, dorsal hands, trunk, anterior thighs, legs, and feet (Figure 1). Wrinkling of axillary plaques was present bilaterally. Multiple thin, brown macules and patches with a collarette of scale were present on the palms, and a few were present on the soles. The buttocks and genitalia were spared.

A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 65-year-old man with end-stage renal disease was seen in the emergency department of this hospital because of a leg injury and a diffuse pruritic rash.

The patient was in poor health, with end-stage renal disease that required hemodialysis. Two years before the current presentation, pathological examination of a renal-biopsy specimen revealed advanced global glomerulosclerosis with tubular atrophy and interstitial fibrosis, as well as collapsing focal and segmental glomerulosclerosis, findings that were superimposed on advanced membranous nephropathy.

Table 1.

Laboratory Data.
Six months before the current presentation, evaluation at this hospital revealed severe hypertension, hyperkalemia, and azotemia. Hemodialysis was initiated. Three months before the current presentation, initial evaluation for renal transplantation revealed that the patient had received a diagnosis of secondary syphilis 11 years earlier (on the basis of a positive rapid plasma reagin [RPR] test at a 1:2 dilution and a negative cerebrospinal fluid analysis), for which he received three doses of intramuscular penicillin G benzathine at 1-week intervals; a follow-up RPR test that was performed 4 years before the current presentation was nonreactive. Results of serologic testing for hepatitis A virus and hepatitis B virus were consistent with protective immunity. Testing was negative for hepatitis C virus and human immunodeficiency virus (HIV) types 1 and 2 and positive for human T-lymphotropic virus type 1 (HTLV-1); other test results are shown in Table 1.

Shortly thereafter, the patient noted a rash on his forearms that he thought was associated with oxycodone, which he was taking for pain associated with the placement of a new hemodialysis fistula. Three weeks before the current presentation, as part of the pretransplantation evaluation, he was seen by an infectious-disease specialist in the outpatient clinic of this hospital. He reported no recent fevers, chills, or weight loss and no history of eczema, psoriasis, or a similar rash. On examination, the vital signs were normal. Nummular (circular or oval), scaly, plaquelike lesions were present on the trunk, arms, and legs, and there was bilateral inguinal lymphadenopathy; the remainder of the examination was normal. An RPR test was reactive at a 1:1 dilution. Renal transplantation was postponed, pending evaluation by a dermatologist. During the next 3 weeks, the rash became pruritic and progressed, with more extensive involvement of the torso, arms, and legs. Three days before the current presentation, while awaiting dermatologic consultation, the patient fell and injured his right leg and left shoulder. Three days later, he came to the emergency department of this hospital because of pain with weight bearing and leg swelling.

The patient had hypertension, a bicuspid aortic valve, and an ascending and aortic-root aneurysm; 13 years before this presentation, he had had a positive tuberculin skin test with a negative chest radiograph. He had had unintentional weight loss of 12 kg during the previous 2 years. His medications were oxycodone with acetaminophen, calcitriol, calcium acetate, clonidine, diltiazem, labetalol, atorvastatin, sertraline, ergocalciferol, a multivitamin, and, during dialysis, epoetin alfa. He also topically applied an emollient and a 5% lidocaine patch. He had no known drug or food allergies. He was born in Haiti and had moved to the United States 30 years earlier. He was married and retired from work in a medical facility. He had smoked cigarettes for 15 years before stopping 20 years earlier and did not drink alcohol or use illicit drugs. His parents had died in their 80s, and his siblings and children were well. There was no family history of skin cancer or other dermatologic diseases.

On examination, the vital signs were normal. The right leg was erythematous, with increased warmth and tense nonpitting edema on the medial proximal leg, point tenderness on the medial leg below the knee, 2+ dorsalis pedis pulses, and no findings suggestive of a thrombosed vein. A diffuse rash was present on the torso, arms, and legs. The remainder of the examination was normal. Blood levels of calcium, phosphorus, and magnesium were normal; other test results are shown in Table 1. A radiograph of the knee and leg showed no evidence of a fracture or dislocation. Noninvasive vascular studies of the legs revealed no evidence of deep or superficial venous thrombosis. Vancomycin was administered intravenously.

Figure 1.

Clinical Photographs.
The patient was admitted to the observation unit of this hospital. On examination by a dermatologist, the skin type was Fitzpatrick type VI. Large, brown, thin, flat-topped papules were widespread, and many coalesced into polygonal plaques. There was a powdery and occasionally thick scale on the neck, arms, axillae, wrists, dorsal hands, trunk, anterior thighs, legs, and feet (Figure 1). Wrinkling of axillary plaques was present bilaterally. Multiple thin, brown macules and patches with a collarette of scale were present on the palms, and a few were present on the soles. The buttocks and genitalia were spared.

A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Mycosis fungoides. The patient's presentation of a diffuse pruritic rash, with large, brown, thin, flat-topped papules that coalesce into polygonal plaques, is characteristic of mycosis fungoides, a type of cutaneous T-cell lymphoma. The presence of a powdery and occasionally thick scale on various parts of the body, as well as the wrinkling of axillary plaques, further supports this diagnosis. The fact that the patient's buttocks and genitalia are spared is also consistent with mycosis fungoides.""
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        ""content"": ""The patient has a diffuse pruritic rash that is not associated with any known allergies or drug reactions. The rash is described as large, brown, thin, flat-topped papules that coalesce into polygonal plaques with a powdery and occasionally thick scale. This description is consistent with lichen planus. The patient's history of HTLV-1 infection is also relevant, as lichen planus has been associated with HTLV-1 infection. The patient's history of end-stage renal disease and hemodialysis could also be contributing factors, as lichen planus has been reported in patients with chronic renal failure and those undergoing hemodialysis.\n\nDiagnosis: Lichen Planus.""
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        ""content"": ""The patient is a 65-year-old man with end-stage renal disease who presents with a pruritic rash. The rash is described as nummular, scaly, plaquelike lesions on the trunk, arms, and legs. The patient also has bilateral inguinal lymphadenopathy. The differential diagnosis for this patient includes psoriasis, eczema, cutaneous T-cell lymphoma, and secondary syphilis. The patient has a history of secondary syphilis, but the rash described is not characteristic of secondary syphilis, which typically presents as a maculopapular rash involving the palms and soles. The patient also has a history of HTLV-1 infection, which is associated with adult T-cell leukemia/lymphoma, a type of cutaneous T-cell lymphoma. The rash described is consistent with cutaneous T-cell lymphoma, which can present as patches, plaques, or tumors. The patient's history of HTLV-1 infection and the presence of lymphadenopathy also support this diagnosis. \n\nDiagnosis: Cutaneous T-cell lymphoma.""
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10.1056/NEJMcpc1600612,Case 18-2016 — A 52-Year-Old Woman with a Pleural Effusion,,Ovarian fibroma and pleural effusion consistent with the Demons–Meigs syndrome.,The Demons–Meigs syndrome.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 52-year-old woman was seen in the pulmonary clinic of this hospital for evaluation of a unilateral pleural effusion that had been seen on magnetic resonance imaging (MRI) of the breasts.

The patient had undergone annual MRI of the breasts since she was 39 years of age because of a strong family history of breast cancer: her mother had received a diagnosis of bilateral lobular breast carcinoma at 60 years of age, her maternal grandmother had received a diagnosis of breast cancer at 70 years of age, a maternal cousin had received a diagnosis of breast cancer in her 30s, and the patient had undergone excisional biopsies of the breasts because of breast fibroadenoma at 20 years of age and fibrocystic changes at 33 years of age. Ten years before the current presentation, she had had dyspnea after undergoing an exploratory laparotomy, rectus diastasis repair, and a right ovarian cystectomy for a 3-mm complex right adnexal mass, which was shown on histologic examination to be a hemorrhagic corpus luteum cyst. That symptom of dyspnea was evaluated with the use of electrocardiography and computed tomography (CT) of the legs and chest for venous thromboembolism; the results of the evaluations were normal. A few months before the current presentation, she had had trauma to the chest wall on the right side during a skiing accident.

The patient had no current dyspnea, orthopnea, cough, or wheeze but had an intermittent and self-limited mild sensation of dyspnea and a rapid heart rate after eating to fullness. She had no chest discomfort but had had discomfort in the right side of her back for a few weeks. Otherwise, she had no constitutional, cardiac, rheumatologic, musculoskeletal, or neurologic symptoms.

The patient’s medical history included a cesarean section (for arrest of fetal descent and chorioamnionitis), two vaginal births after cesarean section, cervical intraepithelial neoplasia (treated with a loop electrosurgical excision procedure), oral herpes simplex virus, supraventricular tachycardia, mild gastroesophageal reflux, a small hiatal hernia (with normal endoscopic results), and muscle fasciculations and paresthesia (which had been evaluated 11 years earlier by a neurologist and had since been quiescent). She was currently up to date on routine cancer screenings and had had normal colonoscopy results and a normal Papanicolaou smear during the previous 6 months. Medications included valacyclovir, as needed. She had allergies to latex, which caused a skin reaction, and sulfa drugs, which caused a rash.

The patient was a lifelong nonsmoker and had never used illicit drugs; she consumed alcohol rarely, on social occasions. She was employed as a physician-scientist, lived with her husband, and had three healthy daughters. Her family owned a farm in New England, where she had previously worked during the summer. She had two dogs at home but no other environmental or chemical exposures. She had traveled to Africa and to China, where she had visited a panda reserve. In addition to the history of breast cancer among her maternal relatives, her father had had prostate cancer, a paternal cousin had had lymphoma, her paternal grandmother had had colon cancer, and multiple maternal and paternal cousins, aunts, and uncles had had esophageal, gastric, renal, lung, and salivary-gland cancers. Furthermore, her mother had osteoporosis and thyroid nodules, her father had a ventriculoperitoneal shunt for normal-pressure hydrocephalus, her paternal grandfather had had Parkinson’s disease, one sister had a ventriculoseptal defect that did not require surgery, another sister had a parathyroid cyst, and a third sister had three adenomatous colonic polyps.

Table 1.

Laboratory Data.
On examination at the pulmonary clinic, the heart rate was 74 beats per minute, the blood pressure 117/56 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The remainder of the examination, including a lung examination, was normal. A basic metabolic profile, a complete blood count, a lipid panel, and results of liver-function tests were normal (Table 1). Pulmonary-function testing revealed normal spirometry and diffusion capacity. Previous imaging studies of the chest were reviewed, and additional studies were obtained.

Figure 1.

Imaging Studies of the Chest.
Dr. William R. Masch: Review of the patient’s previous imaging studies (Figure 1) revealed a long-standing history of a right pleural effusion, which had first been noticed on MRI of the breasts that had been performed 14 years before the current presentation. Contrast-enhanced CT of the thorax, performed as part of her evaluation in the pulmonary clinic, revealed a persistent, small right pleural effusion without abnormal pleural thickening, enhancement, or nodularity. There were several subcentimeter pulmonary nodules that had been unchanged for more than 5 years and were thought to represent noncalcified granulomas or intraparenchymal lymph nodes. The lungs were otherwise normal and had no evidence of cancer.

Dr. Saukkonen: A chest radiograph, obtained with the patient in the right decubitus position, showed trace layering of pleural fluid in the right hemithorax and in the minor fissure. The amount of pleural fluid was insufficient to sample, but serial images showed evidence of stability and cancer screenings were up to date (with no evidence of cancer on imaging studies of the chest), and thus the plan was to obtain repeat images of the chest in 8 weeks.

During ongoing surveillance of the pleural effusion, uterine bleeding, pelvic fullness, bloating, urinary urgency, and dyspareunia developed. Because of the patient’s history of an ovarian mass and her concerns about her strong family history of cancer, additional imaging studies were obtained.

Figure 2.

Imaging Studies of the Pelvis.
Dr. Masch: A pelvic ultrasound study revealed a solid, hypoechoic pelvic mass anterior to the uterus, measuring 9.9 cm in greatest diameter. The left ovary contained a small simple cyst, and the right ovary was not identified. MRI of the pelvis revealed that the pelvic mass made contact with the right broad ligament but not the uterus. Additional findings included a moderate volume of free fluid, a normal endometrium, and a 3.6-cm intramural uterine fibroid in the posterior uterine body. On both T1-weighted and T2-weighted images, the mass was hypointense and showed low-level enhancement throughout (Figure 2). On the basis of the appearance of the pelvic mass on imaging studies, the differential diagnosis was narrow and limited to a fibrous ovarian tumor (e.g., fibroma, fibrothecoma, or cystadenofibroma) or a broad-ligament fibroid. Very few ovarian tumors are both uniformly solid and hypointense on T2-weighted imaging, and thus there is a higher degree of specificity when these features are present.1,2

Dr. Saukkonen: An endometrial biopsy was performed, and examination of the biopsy specimen revealed a proliferative endometrium and fragments of benign endocervix. An additional diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 52-year-old woman was seen in the pulmonary clinic of this hospital for evaluation of a unilateral pleural effusion that had been seen on magnetic resonance imaging (MRI) of the breasts.

The patient had undergone annual MRI of the breasts since she was 39 years of age because of a strong family history of breast cancer: her mother had received a diagnosis of bilateral lobular breast carcinoma at 60 years of age, her maternal grandmother had received a diagnosis of breast cancer at 70 years of age, a maternal cousin had received a diagnosis of breast cancer in her 30s, and the patient had undergone excisional biopsies of the breasts because of breast fibroadenoma at 20 years of age and fibrocystic changes at 33 years of age. Ten years before the current presentation, she had had dyspnea after undergoing an exploratory laparotomy, rectus diastasis repair, and a right ovarian cystectomy for a 3-mm complex right adnexal mass, which was shown on histologic examination to be a hemorrhagic corpus luteum cyst. That symptom of dyspnea was evaluated with the use of electrocardiography and computed tomography (CT) of the legs and chest for venous thromboembolism; the results of the evaluations were normal. A few months before the current presentation, she had had trauma to the chest wall on the right side during a skiing accident.

The patient had no current dyspnea, orthopnea, cough, or wheeze but had an intermittent and self-limited mild sensation of dyspnea and a rapid heart rate after eating to fullness. She had no chest discomfort but had had discomfort in the right side of her back for a few weeks. Otherwise, she had no constitutional, cardiac, rheumatologic, musculoskeletal, or neurologic symptoms.

The patient’s medical history included a cesarean section (for arrest of fetal descent and chorioamnionitis), two vaginal births after cesarean section, cervical intraepithelial neoplasia (treated with a loop electrosurgical excision procedure), oral herpes simplex virus, supraventricular tachycardia, mild gastroesophageal reflux, a small hiatal hernia (with normal endoscopic results), and muscle fasciculations and paresthesia (which had been evaluated 11 years earlier by a neurologist and had since been quiescent). She was currently up to date on routine cancer screenings and had had normal colonoscopy results and a normal Papanicolaou smear during the previous 6 months. Medications included valacyclovir, as needed. She had allergies to latex, which caused a skin reaction, and sulfa drugs, which caused a rash.

The patient was a lifelong nonsmoker and had never used illicit drugs; she consumed alcohol rarely, on social occasions. She was employed as a physician-scientist, lived with her husband, and had three healthy daughters. Her family owned a farm in New England, where she had previously worked during the summer. She had two dogs at home but no other environmental or chemical exposures. She had traveled to Africa and to China, where she had visited a panda reserve. In addition to the history of breast cancer among her maternal relatives, her father had had prostate cancer, a paternal cousin had had lymphoma, her paternal grandmother had had colon cancer, and multiple maternal and paternal cousins, aunts, and uncles had had esophageal, gastric, renal, lung, and salivary-gland cancers. Furthermore, her mother had osteoporosis and thyroid nodules, her father had a ventriculoperitoneal shunt for normal-pressure hydrocephalus, her paternal grandfather had had Parkinson’s disease, one sister had a ventriculoseptal defect that did not require surgery, another sister had a parathyroid cyst, and a third sister had three adenomatous colonic polyps.

Table 1.

Laboratory Data.
On examination at the pulmonary clinic, the heart rate was 74 beats per minute, the blood pressure 117/56 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air. The remainder of the examination, including a lung examination, was normal. A basic metabolic profile, a complete blood count, a lipid panel, and results of liver-function tests were normal (Table 1). Pulmonary-function testing revealed normal spirometry and diffusion capacity. Previous imaging studies of the chest were reviewed, and additional studies were obtained.

Figure 1.

Imaging Studies of the Chest.
Dr. William R. Masch: Review of the patient’s previous imaging studies (Figure 1) revealed a long-standing history of a right pleural effusion, which had first been noticed on MRI of the breasts that had been performed 14 years before the current presentation. Contrast-enhanced CT of the thorax, performed as part of her evaluation in the pulmonary clinic, revealed a persistent, small right pleural effusion without abnormal pleural thickening, enhancement, or nodularity. There were several subcentimeter pulmonary nodules that had been unchanged for more than 5 years and were thought to represent noncalcified granulomas or intraparenchymal lymph nodes. The lungs were otherwise normal and had no evidence of cancer.

Dr. Saukkonen: A chest radiograph, obtained with the patient in the right decubitus position, showed trace layering of pleural fluid in the right hemithorax and in the minor fissure. The amount of pleural fluid was insufficient to sample, but serial images showed evidence of stability and cancer screenings were up to date (with no evidence of cancer on imaging studies of the chest), and thus the plan was to obtain repeat images of the chest in 8 weeks.

During ongoing surveillance of the pleural effusion, uterine bleeding, pelvic fullness, bloating, urinary urgency, and dyspareunia developed. Because of the patient’s history of an ovarian mass and her concerns about her strong family history of cancer, additional imaging studies were obtained.

Figure 2.

Imaging Studies of the Pelvis.
Dr. Masch: A pelvic ultrasound study revealed a solid, hypoechoic pelvic mass anterior to the uterus, measuring 9.9 cm in greatest diameter. The left ovary contained a small simple cyst, and the right ovary was not identified. MRI of the pelvis revealed that the pelvic mass made contact with the right broad ligament but not the uterus. Additional findings included a moderate volume of free fluid, a normal endometrium, and a 3.6-cm intramural uterine fibroid in the posterior uterine body. On both T1-weighted and T2-weighted images, the mass was hypointense and showed low-level enhancement throughout (Figure 2). On the basis of the appearance of the pelvic mass on imaging studies, the differential diagnosis was narrow and limited to a fibrous ovarian tumor (e.g., fibroma, fibrothecoma, or cystadenofibroma) or a broad-ligament fibroid. Very few ovarian tumors are both uniformly solid and hypointense on T2-weighted imaging, and thus there is a higher degree of specificity when these features are present.1,2

Dr. Saukkonen: An endometrial biopsy was performed, and examination of the biopsy specimen revealed a proliferative endometrium and fragments of benign endocervix. An additional diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Meigs' Syndrome\n\nThe patient has a long-standing history of a right pleural effusion, which is not associated with any respiratory symptoms. She also has a solid, hypoechoic pelvic mass, which is likely an ovarian tumor. The combination of a benign ovarian tumor (fibroma, fibrothecoma, or cystadenofibroma) with ascites and pleural effusion, in the absence of metastatic disease, is known as Meigs' syndrome. The pleural effusion in Meigs' syndrome is usually right-sided, as in this patient. The syndrome resolves after removal of the tumor.""
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        ""content"": ""The patient has a long-standing history of a right pleural effusion and a solid, hypoechoic pelvic mass. The mass is hypointense on both T1-weighted and T2-weighted images and shows low-level enhancement throughout. The differential diagnosis based on the appearance of the pelvic mass on imaging studies is narrow and limited to a fibrous ovarian tumor (e.g., fibroma, fibrothecoma, or cystadenofibroma) or a broad-ligament fibroid. Given the patient's strong family history of cancer, the presence of a solid pelvic mass, and the persistent pleural effusion, a malignant ovarian tumor is a strong possibility. \n\nDiagnosis: Ovarian Cancer""
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        ""content"": ""The patient is a 52-year-old woman with a strong family history of breast cancer who presents with a unilateral pleural effusion and a pelvic mass. The differential diagnosis for the pleural effusion includes malignancy, infection, autoimmune disease, and heart failure. Given the patient's strong family history of breast cancer, malignancy is a significant concern. However, the patient's cancer screenings are up to date and there is no evidence of cancer on imaging studies of the chest. Infection and heart failure are less likely given the patient's lack of symptoms and normal cardiac and infectious workup. Autoimmune disease is also less likely given the lack of other systemic symptoms. The differential diagnosis for the pelvic mass includes ovarian cancer, fibroids, and ovarian cysts. Given the patient's strong family history of cancer and the imaging findings, ovarian cancer is a significant concern. However, the imaging findings are also consistent with a fibrous ovarian tumor or a broad-ligament fibroid. \n\nDiagnosis: \nThe final diagnosis is Meigs' syndrome, which is characterized by the triad of a benign ovarian tumor (fibroma, fibrothecoma, or granulosa cell tumor), ascites, and pleural effusion.""
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10.1056/NEJMcpc1516452,Case 17-2016 — A 60-Year-Old Woman with Increasing Dyspnea,,Obliterative bronchiolitis with fibrosis.,Obliterative (constrictive) bronchiolitis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 60-year-old woman was seen in the outpatient pulmonary clinic of this hospital because of increasing dyspnea.

The patient had been well until 2 years before the current evaluation, when episodes of mild, nonproductive coughing developed and occurred multiple times daily. Between 13 months and 10 months before the current evaluation, three febrile illnesses occurred, with temperatures up to 38.9°C. After the third illness, the patient noted dyspnea with exertion. She was seen by her physician for an outpatient evaluation; a chest radiograph was reportedly normal. Oral azithromycin and combined inhaled budesonide–formoterol fumarate dihydrate were administered.

Sixteen days after the outpatient evaluation, dyspnea worsened and was associated with fevers and chest congestion. On evaluation in the emergency department of another hospital, a chest radiograph reportedly showed pulmonary findings suggestive of possible scarring or consolidation; levofloxacin was administered. Ten days later, computed tomography (CT), performed according to a pulmonary emboli protocol, was reportedly negative. An echocardiogram reportedly showed normal left ventricular function and no evidence of pulmonary hypertension.

Table 1.

Results of Pulmonary-Function Testing.
Seven months before this evaluation, results of pulmonary-function tests were thought to be consistent with obstructive lung disease (Table 1). The level of _1-antitrypsin was normal. During the next 4 months, the patient noted increased dyspnea while she was climbing stairs and walking fast. Approximately 4.5 months before this evaluation, pulmonary-function tests were repeated (Table 1). Additional testing revealed allergies to shellfish, dust mites, oak, and birch.

Twenty-seven days before this evaluation, the patient returned to her physician’s office because of increasing dyspnea; albuterol (by nebulizer) and prednisone were administered. One week later, on examination by a pulmonologist at another clinic, the blood pressure was 147/96 mm Hg, the pulse 91 beats per minute, and the oxygen saturation 94% while she was breathing ambient air at rest; the remainder of the examination was normal. Thirteen days before this evaluation, pulmonary-function tests were performed. The results are shown in Table 1.

Dr. John W. Nance: CT of the chest, performed without the administration of contrast material, revealed mild cylindrical bronchiectasis predominantly in the left lower lobe (involving the basilar segments of both lower lobes, the right middle lobe, and the inferior lingular segment), with accompanying mild, diffuse bronchial-wall thickening. There was a small focus of atelectasis or scarring in the medial segment of the right middle lobe, but the lungs otherwise showed no focal abnormality. There was a small hiatal hernia.

Dr. Harris: The patient was referred to the pulmonary clinic of this hospital. On evaluation, she reported increasing dyspnea and fatigue with mild exertion during the previous 3 months that had required rest after she walked one block or climbed one flight of stairs, as well as increasing frequency of upper-airway tightness and, for 4 days before this presentation, a productive cough with green sputum. She also had had fevers and weight loss of 2.5 kg during the previous month. She had hypothyroidism, hypercholesterolemia, hypertensive disorder, recurrent urinary tract infections, and lichen sclerosus, and she had undergone a total knee replacement. She had smoked one to two packs of cigarettes weekly for 10 years as a young adult. Medications were amlodipine, hydrochlorothiazide, levothyroxine, montelukast, a multivitamin, and vitamin C (orally); albuterol and budesonide–formoterol (by inhalation); betamethasone dipropionate ointment, clobetasol propionate ointment, and estradiol vaginal cream (by topical application); cyclosporine ophthalmic emulsion; and fluticasone furoate nasal spray. She had no known allergies to medications. She was married and had two adult children and two dogs. She was a manager in a medical field and reported no known home or occupational exposures. She lived in a suburban area and had traveled to Europe several months earlier. Her mother had Alzheimer’s disease, her sister had the left ventricular noncompaction syndrome, and her children were healthy.

Table 2.

Laboratory Data.
On examination, the temperature was 36.7°C, the blood pressure 132/63 mm Hg, the pulse 81 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 93% while she was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.9. The lungs were clear, and the remainder of the examination was normal. Results of pulmonary-function tests are shown in Table 1. The hematocrit, hemoglobin, platelet count, and blood levels of electrolytes, calcium, glucose, total protein, albumin, globulin, IgA, IgM, IgE, and _1-antitrypsin were normal, as were results of testing for rheumatoid factor, tests of renal and liver function, and serum protein electrophoresis. Testing was negative for human immunodeficiency virus (HIV) antibodies and antigen, antineutrophil cytoplasmic antibodies (ANCA), and antibodies to cyclic citrullinated peptide (CCP), proteinase 3, myeloperoxidase, Scl-70, Jo, Ro, La, Aspergillus fumigatus, A. pullulans, A. flavus, Thermoactinomyces sacchari, T. candidus, T. vulgaris, Micropolyspora faeni, and pigeon sera. Other test results are shown in Table 2.

Figure 1.

Axial CT Scans of the Chest.
Dr. Nance: CT of the chest was performed (Figure 1), after the intravenous administration of contrast material, according to an interstitial lung disease protocol (which includes high-resolution scans obtained during inspiration and expiration and with the patient in the prone position). The scans showed mild cylindrical bronchiectasis predominantly in the lower lobes and mild, diffuse bronchial-wall thickening. There was no difference in the attenuation of the lung parenchyma on expiratory images, as compared with inspiratory images; this finding is suggestive of air trapping. On the expiratory images, there was no lobular or geographic heterogeneity in lung attenuation, a finding indicative of a diffuse process.

Dr. Harris: Eight days after the evaluation in the pulmonary clinic, a bronchoscopic examination was performed. Bronchoalveolar lavage fluid from the right middle lobe and lingula revealed clear and colorless fluid, with three nucleated cells per microliter (34% neutrophils, 24% lymphocytes, 4% monocytes, 6% eosinophils, and 32% macrophages or lining cells) and no evidence of pepsin A or galactomannan antigen. Cytologic examination revealed no viral cytopathic changes, fungal elements, or malignant cells. Gram’s staining revealed very few mixed gram-positive and gram-negative organisms, and cultures were negative for bacterial, viral, and fungal pathogens. Flow cytometry revealed no evidence of a monoclonal B-cell or unusual T-cell population.

During the 11 days after the bronchoscopic examination, increased dyspnea occurred, with associated intermittent low-grade fevers. Test results are shown in Table 2. A chest radiograph showed a patchy right basilar opacity suggestive of atelectasis or aspiration. Albuterol (by nebulizer or by inhaler with a spacer) and a course of azithromycin were administered, and the patient’s condition eventually returned to baseline.

Thirty-four days after the evaluation in the pulmonary clinic of this hospital, flexible bronchoscopic examination revealed prominent scarring between the arytenoids, marked inflammation in the subglottic space, scattered whitish secretions with marked airway inflammation throughout the trachea and right and left bronchial trees, and mild ectasia of the central airways. Bronchoalveolar lavage fluid obtained from the right and left lungs was submitted for microbiologic and cytologic examination and revealed no evidence of viral or bacterial infection.

Two days later, a diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 60-year-old woman was seen in the outpatient pulmonary clinic of this hospital because of increasing dyspnea.

The patient had been well until 2 years before the current evaluation, when episodes of mild, nonproductive coughing developed and occurred multiple times daily. Between 13 months and 10 months before the current evaluation, three febrile illnesses occurred, with temperatures up to 38.9°C. After the third illness, the patient noted dyspnea with exertion. She was seen by her physician for an outpatient evaluation; a chest radiograph was reportedly normal. Oral azithromycin and combined inhaled budesonide–formoterol fumarate dihydrate were administered.

Sixteen days after the outpatient evaluation, dyspnea worsened and was associated with fevers and chest congestion. On evaluation in the emergency department of another hospital, a chest radiograph reportedly showed pulmonary findings suggestive of possible scarring or consolidation; levofloxacin was administered. Ten days later, computed tomography (CT), performed according to a pulmonary emboli protocol, was reportedly negative. An echocardiogram reportedly showed normal left ventricular function and no evidence of pulmonary hypertension.

Table 1.

Results of Pulmonary-Function Testing.
Seven months before this evaluation, results of pulmonary-function tests were thought to be consistent with obstructive lung disease (Table 1). The level of _1-antitrypsin was normal. During the next 4 months, the patient noted increased dyspnea while she was climbing stairs and walking fast. Approximately 4.5 months before this evaluation, pulmonary-function tests were repeated (Table 1). Additional testing revealed allergies to shellfish, dust mites, oak, and birch.

Twenty-seven days before this evaluation, the patient returned to her physician’s office because of increasing dyspnea; albuterol (by nebulizer) and prednisone were administered. One week later, on examination by a pulmonologist at another clinic, the blood pressure was 147/96 mm Hg, the pulse 91 beats per minute, and the oxygen saturation 94% while she was breathing ambient air at rest; the remainder of the examination was normal. Thirteen days before this evaluation, pulmonary-function tests were performed. The results are shown in Table 1.

Dr. John W. Nance: CT of the chest, performed without the administration of contrast material, revealed mild cylindrical bronchiectasis predominantly in the left lower lobe (involving the basilar segments of both lower lobes, the right middle lobe, and the inferior lingular segment), with accompanying mild, diffuse bronchial-wall thickening. There was a small focus of atelectasis or scarring in the medial segment of the right middle lobe, but the lungs otherwise showed no focal abnormality. There was a small hiatal hernia.

Dr. Harris: The patient was referred to the pulmonary clinic of this hospital. On evaluation, she reported increasing dyspnea and fatigue with mild exertion during the previous 3 months that had required rest after she walked one block or climbed one flight of stairs, as well as increasing frequency of upper-airway tightness and, for 4 days before this presentation, a productive cough with green sputum. She also had had fevers and weight loss of 2.5 kg during the previous month. She had hypothyroidism, hypercholesterolemia, hypertensive disorder, recurrent urinary tract infections, and lichen sclerosus, and she had undergone a total knee replacement. She had smoked one to two packs of cigarettes weekly for 10 years as a young adult. Medications were amlodipine, hydrochlorothiazide, levothyroxine, montelukast, a multivitamin, and vitamin C (orally); albuterol and budesonide–formoterol (by inhalation); betamethasone dipropionate ointment, clobetasol propionate ointment, and estradiol vaginal cream (by topical application); cyclosporine ophthalmic emulsion; and fluticasone furoate nasal spray. She had no known allergies to medications. She was married and had two adult children and two dogs. She was a manager in a medical field and reported no known home or occupational exposures. She lived in a suburban area and had traveled to Europe several months earlier. Her mother had Alzheimer’s disease, her sister had the left ventricular noncompaction syndrome, and her children were healthy.

Table 2.

Laboratory Data.
On examination, the temperature was 36.7°C, the blood pressure 132/63 mm Hg, the pulse 81 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 93% while she was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.9. The lungs were clear, and the remainder of the examination was normal. Results of pulmonary-function tests are shown in Table 1. The hematocrit, hemoglobin, platelet count, and blood levels of electrolytes, calcium, glucose, total protein, albumin, globulin, IgA, IgM, IgE, and _1-antitrypsin were normal, as were results of testing for rheumatoid factor, tests of renal and liver function, and serum protein electrophoresis. Testing was negative for human immunodeficiency virus (HIV) antibodies and antigen, antineutrophil cytoplasmic antibodies (ANCA), and antibodies to cyclic citrullinated peptide (CCP), proteinase 3, myeloperoxidase, Scl-70, Jo, Ro, La, Aspergillus fumigatus, A. pullulans, A. flavus, Thermoactinomyces sacchari, T. candidus, T. vulgaris, Micropolyspora faeni, and pigeon sera. Other test results are shown in Table 2.

Figure 1.

Axial CT Scans of the Chest.
Dr. Nance: CT of the chest was performed (Figure 1), after the intravenous administration of contrast material, according to an interstitial lung disease protocol (which includes high-resolution scans obtained during inspiration and expiration and with the patient in the prone position). The scans showed mild cylindrical bronchiectasis predominantly in the lower lobes and mild, diffuse bronchial-wall thickening. There was no difference in the attenuation of the lung parenchyma on expiratory images, as compared with inspiratory images; this finding is suggestive of air trapping. On the expiratory images, there was no lobular or geographic heterogeneity in lung attenuation, a finding indicative of a diffuse process.

Dr. Harris: Eight days after the evaluation in the pulmonary clinic, a bronchoscopic examination was performed. Bronchoalveolar lavage fluid from the right middle lobe and lingula revealed clear and colorless fluid, with three nucleated cells per microliter (34% neutrophils, 24% lymphocytes, 4% monocytes, 6% eosinophils, and 32% macrophages or lining cells) and no evidence of pepsin A or galactomannan antigen. Cytologic examination revealed no viral cytopathic changes, fungal elements, or malignant cells. Gram’s staining revealed very few mixed gram-positive and gram-negative organisms, and cultures were negative for bacterial, viral, and fungal pathogens. Flow cytometry revealed no evidence of a monoclonal B-cell or unusual T-cell population.

During the 11 days after the bronchoscopic examination, increased dyspnea occurred, with associated intermittent low-grade fevers. Test results are shown in Table 2. A chest radiograph showed a patchy right basilar opacity suggestive of atelectasis or aspiration. Albuterol (by nebulizer or by inhaler with a spacer) and a course of azithromycin were administered, and the patient’s condition eventually returned to baseline.

Thirty-four days after the evaluation in the pulmonary clinic of this hospital, flexible bronchoscopic examination revealed prominent scarring between the arytenoids, marked inflammation in the subglottic space, scattered whitish secretions with marked airway inflammation throughout the trachea and right and left bronchial trees, and mild ectasia of the central airways. Bronchoalveolar lavage fluid obtained from the right and left lungs was submitted for microbiologic and cytologic examination and revealed no evidence of viral or bacterial infection.

Two days later, a diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a 60-year-old woman with a history of smoking, presenting with increasing dyspnea, nonproductive cough, and febrile illnesses. She has been treated with antibiotics and inhaled corticosteroids, but her symptoms have worsened. Her CT scans show mild cylindrical bronchiectasis predominantly in the lower lobes and mild, diffuse bronchial-wall thickening. Her pulmonary function tests are consistent with obstructive lung disease. The differential diagnosis for this patient includes chronic obstructive pulmonary disease (COPD), bronchiectasis, asthma, and interstitial lung disease. Given her history of smoking, COPD is a possibility, but her CT findings are more suggestive of bronchiectasis. Asthma could also present with these symptoms, but it is less likely given the patient's age and the lack of improvement with corticosteroids. Interstitial lung disease could also present with dyspnea and cough, but the CT findings are not typical. The bronchoscopic examination revealed prominent scarring between the arytenoids, marked inflammation in the subglottic space, scattered whitish secretions with marked airway inflammation throughout the trachea and right and left bronchial trees, and mild ectasia of the central airways. These findings are consistent with bronchiectasis. \n\nDiagnosis: Bronchiectasis.""
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10.1056/NEJMcpc1516451,Case 16-2016 — A 31-Year-Old Pregnant Woman with Fever,,Listeria monocytogenes bacteremia.,Listeria monocytogenes bacteremia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 31-year-old primigravid woman was seen in the labor and delivery unit of this hospital at 35 weeks of gestation because of fever.

Table 1.

Laboratory Data.
The patient was pregnant with dichorionic, diamniotic twins, and her gestation was complicated by iron-deficiency anemia and hyperemesis. Approximately 3 weeks before this evaluation, mild pruritus of the palms and soles developed. At 32 weeks 5 days of gestation (16 days before this evaluation), the patient was afebrile, had no visible rash, and reported fetal activity; both fetal hearts were heard on auscultation. Laboratory test results are shown in Table 1. A spot urinalysis revealed trace protein. A diagnosis of cholestasis of pregnancy was made, and ursodiol was administered. Four days later, at 33 weeks 2 days of gestation, the patient reported persistent itching, nausea, and occasional vomiting, along with a new pruritic rash on her abdomen that was thought to be consistent with pruritic urticarial papules and plaques of pregnancy. The results of a biophysical profile that assessed fetal well-being were reassuring. The patient returned home.

On the afternoon of the current evaluation, the patient called the obstetrics staff and reported that she had felt “crummy” during the previous week and had noticed decreased fetal activity that day, with a maximum of four movements in 1 hour, despite hydration. She was advised to come to the labor and delivery triage unit for evaluation. On arrival, she reported nausea, decreased appetite, frequent urination (which was unchanged from baseline), subjective fevers, and chills; she did not report bleeding, dysuria, or loss of fluid. She also reported contractions that had occurred during the previous 2 days and had resolved spontaneously. The patient’s medical history included the presence of the sickle cell trait, gastroesophageal reflux disease, and exercise-induced asthma, and she had had dysmenorrhea, a stress fracture of her left tibia, Clostridium difficile infection after clindamycin use, and pancreatitis. Prenatal testing was positive for rubella-specific antibodies and negative for human immunodeficiency virus and hepatitis B virus surface antigen. Her current medications were ursodiol, iron polysaccharide, a prenatal vitamin, doxylamine for sleep, ranitidine, and an albuterol inhaler. She was black and married and worked in the medical field. She did not smoke tobacco, drink alcohol, or use illicit drugs. She did not eat lunch meat or soft cheeses during pregnancy but noted that she consumed well-boiled hot dogs and frequently ate commercial-brand hummus. Her father had had deep venous thromboses; her husband did not carry the sickle-cell trait.

On examination, the temperature was 38.1°C, the blood pressure 120/71 mm Hg, the pulse 66 beats per minute, and the respiratory rate 22 breaths per minute. The abdomen was soft and nontender. The two fetal heart rates were 140 and 150 beats per minute, with accelerations and moderate variability; no decelerations were noted. On tocodynamometry, uterine contractions were noted to occur every 4 minutes initially, and the frequency decreased to every 8 minutes after intravenous hydration. The platelet count and urinalysis were normal; other test results are shown in Table 1. A urine culture was obtained. Acetaminophen was administered, and the infusion of intravenous fluids and fetal monitoring were continued. The fetal heart patterns remained reassuring, and the patient reported increased fetal movement. She was discharged home later that evening and advised to monitor her temperature, to return in 2 days for an evaluation, and to call if symptoms worsened. Induction of labor was scheduled for 5 days after this evaluation.

The next morning, the temperature was again 38.1°C, and the patient self-administered acetaminophen. She spoke with her obstetrician and was referred to the labor and delivery triage unit. On presentation, she reported feeling tired and ill and having nausea, loose stools, rigors, arthralgias, and myalgias. On examination, the temperature was 36.7°C initially and rose to 38.4°C within 30 minutes after her arrival; the blood pressure was 133/71 mm Hg, and the pulse 75 beats per minute. The abdomen was nontender but was noted to be warm to the touch. The cervix was closed and soft, although the uterus was contracting intermittently. The two fetal heart rates were 170 and 180 beats per minute. There was 1+ leg edema. The blood levels of lipase, magnesium, calcium, and phosphorus were normal; other test results are shown in Table 1. Specimens of urine and blood were cultured. Rectal and vaginal swabs were obtained to screen for group B streptococcal colonization. Results of bedside ultrasonography confirmed that both fetuses were in the vertex position. Because the patient was thought to have chorioamnionitis, the decision was made to begin the induction of labor. She was admitted to the labor and delivery unit, and ampicillin, gentamicin, and oxytocin were administered.

During the course of the induction, cough and pleuritic chest pain developed. A chest radiograph was obtained.

Figure 1.

Chest Radiograph.
Dr. Thomas W. Keimig: A portable anteroposterior chest radiograph (Figure 1) showed low lung volumes and patchy right basilar opacities that were thought to most likely represent atelectasis. Pneumonia could not be ruled out.

Dr. Bortoletto: Labor progressed slowly, despite artificial rupture of membranes. Approximately 15 hours after admission, a cesarean section was performed because of a nonreassuring heart-rate pattern in one of the fetuses, and two healthy infants were delivered. The Apgar scores at 1 and 5 minutes were 8 and 9, respectively, for the first baby and 7 and 8 for the second baby.

Diagnostic test results were received.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 31-year-old primigravid woman was seen in the labor and delivery unit of this hospital at 35 weeks of gestation because of fever.

Table 1.

Laboratory Data.
The patient was pregnant with dichorionic, diamniotic twins, and her gestation was complicated by iron-deficiency anemia and hyperemesis. Approximately 3 weeks before this evaluation, mild pruritus of the palms and soles developed. At 32 weeks 5 days of gestation (16 days before this evaluation), the patient was afebrile, had no visible rash, and reported fetal activity; both fetal hearts were heard on auscultation. Laboratory test results are shown in Table 1. A spot urinalysis revealed trace protein. A diagnosis of cholestasis of pregnancy was made, and ursodiol was administered. Four days later, at 33 weeks 2 days of gestation, the patient reported persistent itching, nausea, and occasional vomiting, along with a new pruritic rash on her abdomen that was thought to be consistent with pruritic urticarial papules and plaques of pregnancy. The results of a biophysical profile that assessed fetal well-being were reassuring. The patient returned home.

On the afternoon of the current evaluation, the patient called the obstetrics staff and reported that she had felt “crummy” during the previous week and had noticed decreased fetal activity that day, with a maximum of four movements in 1 hour, despite hydration. She was advised to come to the labor and delivery triage unit for evaluation. On arrival, she reported nausea, decreased appetite, frequent urination (which was unchanged from baseline), subjective fevers, and chills; she did not report bleeding, dysuria, or loss of fluid. She also reported contractions that had occurred during the previous 2 days and had resolved spontaneously. The patient’s medical history included the presence of the sickle cell trait, gastroesophageal reflux disease, and exercise-induced asthma, and she had had dysmenorrhea, a stress fracture of her left tibia, Clostridium difficile infection after clindamycin use, and pancreatitis. Prenatal testing was positive for rubella-specific antibodies and negative for human immunodeficiency virus and hepatitis B virus surface antigen. Her current medications were ursodiol, iron polysaccharide, a prenatal vitamin, doxylamine for sleep, ranitidine, and an albuterol inhaler. She was black and married and worked in the medical field. She did not smoke tobacco, drink alcohol, or use illicit drugs. She did not eat lunch meat or soft cheeses during pregnancy but noted that she consumed well-boiled hot dogs and frequently ate commercial-brand hummus. Her father had had deep venous thromboses; her husband did not carry the sickle-cell trait.

On examination, the temperature was 38.1°C, the blood pressure 120/71 mm Hg, the pulse 66 beats per minute, and the respiratory rate 22 breaths per minute. The abdomen was soft and nontender. The two fetal heart rates were 140 and 150 beats per minute, with accelerations and moderate variability; no decelerations were noted. On tocodynamometry, uterine contractions were noted to occur every 4 minutes initially, and the frequency decreased to every 8 minutes after intravenous hydration. The platelet count and urinalysis were normal; other test results are shown in Table 1. A urine culture was obtained. Acetaminophen was administered, and the infusion of intravenous fluids and fetal monitoring were continued. The fetal heart patterns remained reassuring, and the patient reported increased fetal movement. She was discharged home later that evening and advised to monitor her temperature, to return in 2 days for an evaluation, and to call if symptoms worsened. Induction of labor was scheduled for 5 days after this evaluation.

The next morning, the temperature was again 38.1°C, and the patient self-administered acetaminophen. She spoke with her obstetrician and was referred to the labor and delivery triage unit. On presentation, she reported feeling tired and ill and having nausea, loose stools, rigors, arthralgias, and myalgias. On examination, the temperature was 36.7°C initially and rose to 38.4°C within 30 minutes after her arrival; the blood pressure was 133/71 mm Hg, and the pulse 75 beats per minute. The abdomen was nontender but was noted to be warm to the touch. The cervix was closed and soft, although the uterus was contracting intermittently. The two fetal heart rates were 170 and 180 beats per minute. There was 1+ leg edema. The blood levels of lipase, magnesium, calcium, and phosphorus were normal; other test results are shown in Table 1. Specimens of urine and blood were cultured. Rectal and vaginal swabs were obtained to screen for group B streptococcal colonization. Results of bedside ultrasonography confirmed that both fetuses were in the vertex position. Because the patient was thought to have chorioamnionitis, the decision was made to begin the induction of labor. She was admitted to the labor and delivery unit, and ampicillin, gentamicin, and oxytocin were administered.

During the course of the induction, cough and pleuritic chest pain developed. A chest radiograph was obtained.

Figure 1.

Chest Radiograph.
Dr. Thomas W. Keimig: A portable anteroposterior chest radiograph (Figure 1) showed low lung volumes and patchy right basilar opacities that were thought to most likely represent atelectasis. Pneumonia could not be ruled out.

Dr. Bortoletto: Labor progressed slowly, despite artificial rupture of membranes. Approximately 15 hours after admission, a cesarean section was performed because of a nonreassuring heart-rate pattern in one of the fetuses, and two healthy infants were delivered. The Apgar scores at 1 and 5 minutes were 8 and 9, respectively, for the first baby and 7 and 8 for the second baby.

Diagnostic test results were received.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Listeria monocytogenes infection. The patient's symptoms of fever, myalgias, and arthralgias, along with her consumption of hot dogs and hummus (foods known to potentially carry Listeria), suggest a Listeria infection. This is further supported by her presentation of chorioamnionitis, as Listeria can cross the placental barrier and cause this condition. Her symptoms did not improve with the administration of antibiotics that are not effective against Listeria, further supporting this diagnosis.""
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        ""content"": ""The patient is a pregnant woman with fever, nausea, loose stools, rigors, arthralgias, and myalgias. She also has a history of consuming commercial-brand hummus frequently. The symptoms and the food history suggest a foodborne illness. Listeria monocytogenes is a bacterium that can cause foodborne illness and is commonly found in ready-to-eat foods like hot dogs and deli meats, as well as in dairy products like soft cheeses. It can also be found in hummus. Listeria infection can cause flu-like symptoms, including fever, muscle aches, and diarrhea. It can also cause complications in pregnancy, including preterm labor, infection of the newborn, and even stillbirth. Given the patient's symptoms and food history, a Listeria infection is a likely diagnosis.\n\nDiagnosis: Listeria monocytogenes infection.""
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        ""content"": ""The patient is a 31-year-old pregnant woman presenting with fever, nausea, decreased appetite, and a pruritic rash on her abdomen. She also reports decreased fetal activity and contractions. Her medical history includes sickle cell trait, gastroesophageal reflux disease, exercise-induced asthma, and pancreatitis. She has been diagnosed with cholestasis of pregnancy and is currently on ursodiol. The differential diagnosis for this patient includes chorioamnionitis, preterm labor, preeclampsia, and viral or bacterial infection. The patient's symptoms of fever, nausea, and decreased fetal activity, along with her uterine contractions, are concerning for chorioamnionitis. However, her urinalysis is normal, which makes a urinary tract infection less likely. Her blood pressure is also normal, which makes preeclampsia less likely. The patient's symptoms of fever and malaise, along with her elevated white blood cell count, are concerning for a systemic infection. However, her blood cultures are negative, which makes a bacterial infection less likely. The patient's symptoms of fever, nausea, and decreased fetal activity, along with her uterine contractions, are concerning for preterm labor. However, her cervix is closed, which makes preterm labor less likely. The patient's symptoms of fever, nausea, and decreased fetal activity, along with her uterine contractions, are concerning for chorioamnionitis. This is further supported by the fact that her symptoms improved after delivery of the babies.\n\nDiagnosis: Chorioamnionitis.""
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10.1056/NEJMcpc1516449,Case 15-2016 — A 32-Year-Old Man with Olfactory Hallucinations and Paresthesias,,Neurosarcoidosis (focal sarcoid granulomatous encephalitis).,"Cerebral granuloma, probably sarcoidosis, with other causes not excluded.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 32-year-old man was seen in an outpatient clinic of this hospital because of olfactory hallucinations, intermittent numbness and paresthesias on the left side, and a mass in the right temporal lobe.

The patient had been well until approximately 1 year before admission, when olfactory hallucinations (including sulfur and burning odors) developed, along with associated nausea. Episodes occurred every few days and lasted for approximately 2 minutes. Approximately 6 weeks before this evaluation, transient daily episodes of numbness and paresthesias on the left side began. Results of a neurologic examination performed at another hospital were reportedly normal. Magnetic resonance imaging (MRI) of the head reportedly revealed a partially enhancing mass in the medial aspect of the right temporal lobe; fluid-attenuated inversion recovery (FLAIR) images showed extension of the abnormality into the insula and basal ganglia. Levetiracetam was administered for management of suspected focal seizures, and the patient was referred to this hospital for evaluation.

The patient was right-handed. He had pain associated with left molar caries (for which a root canal was planned) and a history of attention deficit–hyperactivity disorder. He reported no changes in his skin or vision, joint pain, dry mouth, decreased lacrimation, or respiratory symptoms. During childhood, he had had ophthalmologic surgery on his left lens after an injury. Medications included levetiracetam and dextroamphetamine. He had no known allergies. He lived alone and worked in an office. He drank alcohol in moderation, had smoked cigarettes briefly more than 10 years earlier, and did not use illicit drugs. He was of both African-American and Caribbean ancestry, was born in the United States, and had not traveled to the Caribbean. There was no family history of autoimmune diseases, malignant tumors, or migraine headache.

On examination, there were postsurgical changes in the patient’s left pupil; the right pupil was reactive to light. The remainder of the examination was normal, including examination of the visual fields, strength, coordination, and balance. A complete blood count and urinalysis were normal, as were blood levels of electrolytes, calcium, and glucose and results of coagulation and renal-function tests. An electrocardiogram showed a normal sinus rhythm and met the voltage criteria for left-ventricular hypertrophy in the precordial leads. A chest radiograph was normal.

Figure 1.

MRI of the Head.
Dr. George J. Hunter: MRI of the head was performed with and without the administration of contrast material (Figure 1). An irregularly marginated and nodular focus of enhancement was present along the medial right temporal lobe, extending into the adjacent tissue of the right cerebral peduncle and abutting the right middle cerebral artery. FLAIR-imaging sequences showed only a moderate amount of abnormal signal in the brain parenchyma adjacent to the enhancing foci. Sagittal and coronal views also showed leptomeningeal nodules of enhancement along the inferior margin of the right basis pontis and, more inferiorly, along the right side of the medulla oblongata.

In addition, perfusion imaging and multivoxel magnetic resonance spectroscopy were performed. The results of the spectroscopy were essentially normal, and the perfusion imaging was unhelpful.

Dr. Vodopivec: A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 32-year-old man was seen in an outpatient clinic of this hospital because of olfactory hallucinations, intermittent numbness and paresthesias on the left side, and a mass in the right temporal lobe.

The patient had been well until approximately 1 year before admission, when olfactory hallucinations (including sulfur and burning odors) developed, along with associated nausea. Episodes occurred every few days and lasted for approximately 2 minutes. Approximately 6 weeks before this evaluation, transient daily episodes of numbness and paresthesias on the left side began. Results of a neurologic examination performed at another hospital were reportedly normal. Magnetic resonance imaging (MRI) of the head reportedly revealed a partially enhancing mass in the medial aspect of the right temporal lobe; fluid-attenuated inversion recovery (FLAIR) images showed extension of the abnormality into the insula and basal ganglia. Levetiracetam was administered for management of suspected focal seizures, and the patient was referred to this hospital for evaluation.

The patient was right-handed. He had pain associated with left molar caries (for which a root canal was planned) and a history of attention deficit–hyperactivity disorder. He reported no changes in his skin or vision, joint pain, dry mouth, decreased lacrimation, or respiratory symptoms. During childhood, he had had ophthalmologic surgery on his left lens after an injury. Medications included levetiracetam and dextroamphetamine. He had no known allergies. He lived alone and worked in an office. He drank alcohol in moderation, had smoked cigarettes briefly more than 10 years earlier, and did not use illicit drugs. He was of both African-American and Caribbean ancestry, was born in the United States, and had not traveled to the Caribbean. There was no family history of autoimmune diseases, malignant tumors, or migraine headache.

On examination, there were postsurgical changes in the patient’s left pupil; the right pupil was reactive to light. The remainder of the examination was normal, including examination of the visual fields, strength, coordination, and balance. A complete blood count and urinalysis were normal, as were blood levels of electrolytes, calcium, and glucose and results of coagulation and renal-function tests. An electrocardiogram showed a normal sinus rhythm and met the voltage criteria for left-ventricular hypertrophy in the precordial leads. A chest radiograph was normal.

Figure 1.

MRI of the Head.
Dr. George J. Hunter: MRI of the head was performed with and without the administration of contrast material (Figure 1). An irregularly marginated and nodular focus of enhancement was present along the medial right temporal lobe, extending into the adjacent tissue of the right cerebral peduncle and abutting the right middle cerebral artery. FLAIR-imaging sequences showed only a moderate amount of abnormal signal in the brain parenchyma adjacent to the enhancing foci. Sagittal and coronal views also showed leptomeningeal nodules of enhancement along the inferior margin of the right basis pontis and, more inferiorly, along the right side of the medulla oblongata.

In addition, perfusion imaging and multivoxel magnetic resonance spectroscopy were performed. The results of the spectroscopy were essentially normal, and the perfusion imaging was unhelpful.

Dr. Vodopivec: A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of olfactory hallucinations, intermittent numbness and paresthesias on the left side, and a mass in the right temporal lobe suggest a neurological issue. The MRI results confirm the presence of a mass in the right temporal lobe, extending into the insula and basal ganglia. The irregularly marginated and nodular focus of enhancement along the medial right temporal lobe, extending into the adjacent tissue of the right cerebral peduncle and abutting the right middle cerebral artery, as well as leptomeningeal nodules of enhancement along the inferior margin of the right basis pontis and along the right side of the medulla oblongata, suggest a neoplastic process. The normal results of the spectroscopy and the unhelpful perfusion imaging do not provide additional information for the diagnosis. Given the patient's symptoms and the MRI findings, a brain tumor is the most likely diagnosis. \n\nDiagnosis: Brain tumor.""
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        ""content"": ""The patient's symptoms of olfactory hallucinations, intermittent numbness and paresthesias on the left side, and a mass in the right temporal lobe suggest a neurological issue. The MRI results confirm the presence of a mass in the right temporal lobe, extending into the adjacent tissue of the right cerebral peduncle and abutting the right middle cerebral artery. The leptomeningeal nodules of enhancement along the inferior margin of the right basis pontis and, more inferiorly, along the right side of the medulla oblongata, suggest a neoplastic process. The normal results of the spectroscopy and the unhelpful perfusion imaging do not provide additional information for the diagnosis. Given the patient's symptoms and the MRI findings, a brain tumor is the most likely diagnosis. \n\nDiagnosis: Brain tumor.""
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        ""content"": ""The patient is a 32-year-old man presenting with olfactory hallucinations, intermittent numbness and paresthesias on the left side, and a mass in the right temporal lobe. The differential diagnosis for this patient includes brain tumor, focal seizures, multiple sclerosis, and stroke. The patient's MRI shows an irregularly marginated and nodular focus of enhancement along the medial right temporal lobe, extending into the adjacent tissue of the right cerebral peduncle and abutting the right middle cerebral artery. This is suggestive of a brain tumor. The patient's symptoms of olfactory hallucinations and intermittent numbness and paresthesias are also consistent with a brain tumor. The patient's symptoms are not consistent with multiple sclerosis, which typically presents with optic neuritis, motor symptoms, and sensory symptoms in a disseminated pattern. The patient's symptoms are also not consistent with a stroke, which would typically present with sudden onset of symptoms. The patient's symptoms are partially consistent with focal seizures, which can cause sensory disturbances and olfactory hallucinations. However, the patient's MRI findings are not typical for seizures, which would not typically cause a mass in the right temporal lobe. Therefore, the most likely diagnosis is a brain tumor.\n\nDiagnosis: Brain tumor.""
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10.1056/NEJMcpc1514473,Case 14-2016 — A 37-Year-Old Woman with Adult-Onset Psychosis,,Celiac disease in histologic remission.,Celiac disease complicated by psychosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 37-year-old woman was admitted to a psychiatric hospital for adult-onset psychosis.

The patient had been healthy and studying for a doctoral degree when she began having symptoms of psychosis. Her first symptom was a belief that “people were talking about her” as part of a larger “conspiracy” in which family, friends, and random people were part of a “game” and acting out “scenes” for her. She had had stress associated with her schooling and had contemplated changing schools. However, she had not had other symptoms of anxiety or depression, neurovegetative symptoms, or auditory or visual hallucinations.

A few months later, the patient’s apartment was burglarized and vandalized; her parents were the only other people with a key, and she believed they were involved. Because of threats she made against family members, she was admitted to an inpatient state psychiatric facility. A diagnosis of psychotic disorder, possibly paranoid schizophrenia, was rendered.

An evaluation for causes of the disorder revealed evidence of marked iron-deficiency anemia, including an iron level of 18 _g per deciliter (3 _mol per liter; reference range, 45 to 182 _g per deciliter [8 to 33 _mol per liter]), a ferritin level of 6 ng per milliliter (reference range, 11 to 306), and a transferrin saturation of 3.7% (reference range, 11.0 to 50.0). The evaluation also revealed vitamin deficiencies, including a vitamin B12 level of 167 pg per milliliter (reference range, 182 to 803) and a vitamin D2 level of 10 ng per milliliter (reference value, >32).

Before admission to the state psychiatric facility, the patient had had no history of psychiatric disease. She had a remote history of a left-foot fracture and had undergone a right oophorectomy at 17 years of age for torsion of the ovary. She took no medications. Her mother recalled her being a “perfectionist,” especially during her late teenage years. The patient had reported an unintentional weight loss of 9 kg over an unspecified period of time, despite self-described polyphagia and some hair thinning. She did not have diarrhea. There was no history of head injury or seizure, menopausal symptoms after the oophorectomy, or social withdrawal. Her mother had systemic lupus erythematosus, her sister had hypothyroidism and hyperparathyroidism, her maternal grandfather had diabetes, and an aunt had breast cancer. There was no family history of psychiatric disease.

The patient had been previously employed in human resources and had lived alone. She had traveled to the southern United States, coastal Massachusetts, and New York City but not abroad. She followed a pescatarian diet that included dairy foods and an egg daily as part of a lunch salad. She drank one alcoholic beverage per month, did not smoke cigarettes but had used marijuana, and drank two caffeinated beverages daily.

After a 1-month inpatient stay at the state psychiatric facility, the patient was discharged. Her medications included risperidone, sertraline, ferrous sulfate, calcium, vitamin D, vitamin C, and a multivitamin. At a routine follow-up visit 6 weeks after discharge, the patient was evaluated by an internist at her primary care physician’s office, who found her to be excessively thin.

On examination, a thyroid nodule was identified, which prompted consultation with an endocrinologist. A biopsy of the nodule was performed, and examination of the biopsy specimen revealed evidence of Hashimoto’s thyroiditis and papillary thyroid carcinoma. Radioactive iodine ablation was suggested, but the patient opted for total thyroidectomy. After the thyroid surgery and despite the administration of escalating doses of oral levothyroxine, the patient’s thyrotropin level reportedly remained high (value not available) and the free thyroxine level was 0.73 ng per deciliter (9 pmol per liter; reference range, 0.80 to 1.80 ng per deciliter [10 to 23 pmol per liter]). Several weeks later, after further dose escalation of levothyroxine, the free thyroxine level was 0.80 ng per deciliter (10 pmol per liter).

A limited follow-up examination that was performed by the endocrinologist 6 months after the initial consultation revealed a height of 167.6 cm, a weight of 45 kg, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 16.1. The patient was afebrile and had a regular pulse of 75 beats per minute and a blood pressure of 90/60 mm Hg. The thyroidectomy scar was well-healed, and the remainder of the examination was reportedly normal. However, the patient’s psychiatric symptoms were believed to be poorly controlled by antipsychotic medications, and it was unclear whether her thyroid conditions were related to her psychosis.

Diagnostic tests were performed, and the patient presented to this hospital for further evaluation
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 37-year-old woman was admitted to a psychiatric hospital for adult-onset psychosis.

The patient had been healthy and studying for a doctoral degree when she began having symptoms of psychosis. Her first symptom was a belief that “people were talking about her” as part of a larger “conspiracy” in which family, friends, and random people were part of a “game” and acting out “scenes” for her. She had had stress associated with her schooling and had contemplated changing schools. However, she had not had other symptoms of anxiety or depression, neurovegetative symptoms, or auditory or visual hallucinations.

A few months later, the patient’s apartment was burglarized and vandalized; her parents were the only other people with a key, and she believed they were involved. Because of threats she made against family members, she was admitted to an inpatient state psychiatric facility. A diagnosis of psychotic disorder, possibly paranoid schizophrenia, was rendered.

An evaluation for causes of the disorder revealed evidence of marked iron-deficiency anemia, including an iron level of 18 _g per deciliter (3 _mol per liter; reference range, 45 to 182 _g per deciliter [8 to 33 _mol per liter]), a ferritin level of 6 ng per milliliter (reference range, 11 to 306), and a transferrin saturation of 3.7% (reference range, 11.0 to 50.0). The evaluation also revealed vitamin deficiencies, including a vitamin B12 level of 167 pg per milliliter (reference range, 182 to 803) and a vitamin D2 level of 10 ng per milliliter (reference value, >32).

Before admission to the state psychiatric facility, the patient had had no history of psychiatric disease. She had a remote history of a left-foot fracture and had undergone a right oophorectomy at 17 years of age for torsion of the ovary. She took no medications. Her mother recalled her being a “perfectionist,” especially during her late teenage years. The patient had reported an unintentional weight loss of 9 kg over an unspecified period of time, despite self-described polyphagia and some hair thinning. She did not have diarrhea. There was no history of head injury or seizure, menopausal symptoms after the oophorectomy, or social withdrawal. Her mother had systemic lupus erythematosus, her sister had hypothyroidism and hyperparathyroidism, her maternal grandfather had diabetes, and an aunt had breast cancer. There was no family history of psychiatric disease.

The patient had been previously employed in human resources and had lived alone. She had traveled to the southern United States, coastal Massachusetts, and New York City but not abroad. She followed a pescatarian diet that included dairy foods and an egg daily as part of a lunch salad. She drank one alcoholic beverage per month, did not smoke cigarettes but had used marijuana, and drank two caffeinated beverages daily.

After a 1-month inpatient stay at the state psychiatric facility, the patient was discharged. Her medications included risperidone, sertraline, ferrous sulfate, calcium, vitamin D, vitamin C, and a multivitamin. At a routine follow-up visit 6 weeks after discharge, the patient was evaluated by an internist at her primary care physician’s office, who found her to be excessively thin.

On examination, a thyroid nodule was identified, which prompted consultation with an endocrinologist. A biopsy of the nodule was performed, and examination of the biopsy specimen revealed evidence of Hashimoto’s thyroiditis and papillary thyroid carcinoma. Radioactive iodine ablation was suggested, but the patient opted for total thyroidectomy. After the thyroid surgery and despite the administration of escalating doses of oral levothyroxine, the patient’s thyrotropin level reportedly remained high (value not available) and the free thyroxine level was 0.73 ng per deciliter (9 pmol per liter; reference range, 0.80 to 1.80 ng per deciliter [10 to 23 pmol per liter]). Several weeks later, after further dose escalation of levothyroxine, the free thyroxine level was 0.80 ng per deciliter (10 pmol per liter).

A limited follow-up examination that was performed by the endocrinologist 6 months after the initial consultation revealed a height of 167.6 cm, a weight of 45 kg, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 16.1. The patient was afebrile and had a regular pulse of 75 beats per minute and a blood pressure of 90/60 mm Hg. The thyroidectomy scar was well-healed, and the remainder of the examination was reportedly normal. However, the patient’s psychiatric symptoms were believed to be poorly controlled by antipsychotic medications, and it was unclear whether her thyroid conditions were related to her psychosis.

Diagnostic tests were performed, and the patient presented to this hospital for further evaluation
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of psychosis, weight loss despite polyphagia, hair thinning, and iron-deficiency anemia, along with the discovery of a thyroid nodule and subsequent diagnosis of Hashimoto's thyroiditis and papillary thyroid carcinoma, suggest a possible autoimmune or endocrine cause for her psychiatric symptoms. The patient's psychiatric symptoms did not improve with antipsychotic medications, further suggesting a non-psychiatric cause. The patient's high thyrotropin level and low free thyroxine level despite levothyroxine treatment suggest poor absorption or a malabsorption syndrome. The patient's pescatarian diet and vitamin deficiencies suggest a possible nutritional cause. The combination of psychiatric symptoms, malabsorption, and nutritional deficiencies is suggestive of celiac disease, which can cause all these symptoms. \n\nDiagnosis: Celiac disease.""
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        ""content"": ""The patient's symptoms of psychosis, weight loss despite polyphagia, hair thinning, and the presence of a thyroid nodule suggest a thyroid-related condition. The biopsy confirmed Hashimoto's thyroiditis and papillary thyroid carcinoma. Despite treatment, the patient's thyrotropin level remained high and the free thyroxine level was low, indicating hypothyroidism. Hypothyroidism can cause psychiatric symptoms, including psychosis, especially when severe. This is known as myxedema psychosis. The patient's symptoms did not improve with antipsychotic medications, further suggesting that the psychosis was due to a physical rather than psychiatric condition. \n\nDiagnosis: Myxedema psychosis due to Hashimoto's thyroiditis and papillary thyroid carcinoma.""
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}",Myxedema psychosis due to Hashimoto's thyroiditis and papillary thyroid carcinom,N,"{
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        ""content"": ""The patient is a 37-year-old woman presenting with adult-onset psychosis, marked iron-deficiency anemia, vitamin deficiencies, and a history of unintentional weight loss despite self-described polyphagia. She also has a thyroid nodule identified, which was diagnosed as Hashimoto\u2019s thyroiditis and papillary thyroid carcinoma. The differential diagnosis for this patient includes paranoid schizophrenia, severe depression with psychotic features, anorexia nervosa, and autoimmune thyroid disease. The patient's symptoms of psychosis began before any physical symptoms were noted, which could suggest a primary psychiatric disorder such as paranoid schizophrenia or severe depression with psychotic features. However, her lack of other symptoms of depression and the absence of auditory or visual hallucinations make these diagnoses less likely. The patient's significant weight loss, despite reported polyphagia, along with her perfectionist tendencies and excessive thinness, suggest the possibility of anorexia nervosa. This eating disorder can cause severe malnutrition, leading to a variety of physical symptoms including anemia and vitamin deficiencies. However, the patient's thyroid nodule and subsequent diagnoses of Hashimoto\u2019s thyroiditis and papillary thyroid carcinoma suggest an autoimmune thyroid disease. Autoimmune thyroid disease can cause a variety of psychiatric symptoms, including psychosis, particularly if the disease is severe or poorly controlled. The patient's persistent high thyrotropin level despite levothyroxine treatment suggests that her thyroid disease may not be well controlled. Given the patient's physical and psychiatric symptoms, as well as her family history of autoimmune disease, it seems likely that her psychosis is related to her thyroid disease.\n\nDiagnosis: Psychosis due to autoimmune thyroid disease.""
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10.1056/NEJMcpc1501151,Case 13-2016 — A 49-Year-Old Woman with Sudden Hemiplegia and Aphasia during a Transatlantic Flight,,"Acute ischemic stroke, caused by paradoxical embolism through a patent foramen ovale, in a patient with the May–Thurner syndrome and a hypercoagulable state due to an occult renal-cell carcinoma.","Acute ischemic stroke, caused by paradoxical embolism through a patent foramen ovale, in a patient with the May–Thurner syndrome and a hypercoagulable state due to an occult renal-cell carcinoma.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 49-year-old woman was brought to the emergency department of this hospital after the sudden onset of hemiplegia and aphasia during a transatlantic flight.

The patient had been well until approximately 2 hours before presentation, when severe weakness developed on the right side and she lost the ability to speak. The patient’s husband alerted a flight attendant, and a passenger who was a physician informed the crew that they must transport her to a hospital within 3 hours to enable proper treatment. The pilot accelerated the aircraft to arrive in Boston within 2 hours after symptom onset. The patient was evaluated by emergency medical technicians on her arrival at the airport. The blood pressure was 146/82 mm Hg, and the pulse 100 beats per minute and regular. She had a right facial droop and was unable to lift her right arm. The capillary blood glucose level was 151 mg per deciliter (8.4 mmol per liter). Boston Emergency Medical Services (EMS) provided this hospital with prearrival notification, and the patient was brought by ambulance to the emergency department, where a multidisciplinary team had been assembled.

The patient had a history of migraine headaches, asthma, and recurrent intermittent swelling of her left thigh every few months since childhood, when she had undergone the surgical excision of a birthmark on the left inner thigh that had frequently bled. Medications were aspirin several days per week (for headaches) and asthma inhalers. She had no known allergies. She was traveling with her husband, who provided the history. She did not smoke cigarettes. There was no family history of hematologic disease or coagulation abnormalities.

On the initial examination, the patient was alert and followed simple commands but answered “yup” to all questions. The blood pressure was 146/77 mm Hg, the pulse 121 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 96% while she was breathing oxygen through a nonrebreather face mask at a rate of 4 liters per minute; the temperature was normal. The pupils were 3 mm and reactive to light. There was a left-gaze preference and a slight right facial droop. The right arm was flaccid (with a strength of 0 on a scale of 0 to 5, with 5 indicating normal strength), and the right leg had minor weakness (with a strength of 5_ out of 5). The strength on the left side and the remainder of the examination were normal.

The white-cell count was 11,900 per cubic millimeter (reference range, 4500 to 11,000), with 76.3% neutrophils. The troponin T level was 0.23 ng per milliliter (reference value, <0.03), the carbon dioxide level was 21.6 mmol per liter (reference range, 23.0 to 31.9), and the phosphorus level was 2.1 mg per deciliter (0.68 mmol per liter; reference range, 2.6 to 4.5 mg per deciliter [0.84 to 1.45 mmol per liter]). The hematocrit, hemoglobin level, platelet count, prothrombin time, and prothrombin-time international normalized ratio were normal, as were blood levels of other electrolytes, calcium, magnesium, and lipase and results of renal-function tests, a toxicology screening, and electrocardiography.

A diagnosis of acute ischemic stroke due to occlusion of the left middle cerebral artery was made. The initial score on the National Institutes of Health Stroke Scale (NIHSS) was 14 (on a scale of 0 to 42, with higher scores indicating more severe deficit).

Dr. R. Gilberto Gonzalez: Computed tomography (CT) of the head, performed without the administration of contrast material, revealed mild loss of gray–white differentiation in the left insula that was thought to be related to acute infarction, hyperdensity of the proximal left middle cerebral artery and the terminus of the left internal carotid artery, a small hypodensity in the left thalamus, and no evidence of intracerebral hemorrhage or mass lesion. A bolus of 5.4 mg of tissue plasminogen activator (t-PA) was administered intravenously 13 minutes after the patient’s arrival, and then an infusion of 52.2 mg of t-PA was administered over a 1-hour period, for a total of 0.9 mg of t-PA per kilogram of body weight.

Figure 1.

Imaging Studies of the Head.
CT angiography of the head and neck, performed immediately after the bolus of t-PA was administered, revealed a diminutive proximal left internal carotid artery and no enhancement of the left internal carotid artery as it entered the base of the skull, as well as thrombus in the left paraclinoid and supraclinoid internal carotid artery that extended into the left middle cerebral artery (M1 and proximal M2 segments), with reconstitution of the sylvian branches and prominent collateral vessels (Figure 1A). On delayed images, slow flow was seen in the distal left cervical internal carotid artery and the petrous and cavernous segments of the left internal carotid artery, and a tiny focus of hypoenhancement was seen in the distal aspect of the petrous segment of the right internal carotid artery, a finding that possibly represented a small thrombus. Fifty-one minutes after the patient’s arrival, magnetic resonance imaging (MRI) of the head, performed without the administration of intravenous contrast material, revealed restricted diffusion involving the left insula (Figure 1B), posterior limb of the left internal capsule, and left medial temporal lobe, as well as punctate foci of restricted diffusion in the left frontal and parietal lobes and the right frontal lobe near the vertex; these findings are consistent with infarction involving the territory of the left middle cerebral artery. The volume of the diffusion abnormality was less than 25 ml, and therefore the patient was likely to benefit from endovascular thrombectomy.1 On fluid-attenuated inversion recovery images, there was hyperintensity in the branches of the left middle cerebral artery and in the petrous and cavernous segments of the left internal carotid artery; these findings are consistent with slow flow, which was seen on the earlier CT angiography. The presence of a focal area of susceptibility effect in the proximal left middle cerebral artery was consistent with the occlusive thrombus in the middle cerebral artery.

The NIHSS score was unchanged despite the administration of t-PA. One hour after the patient’s arrival, she was transported to an angiography-equipped operating room for endovascular thrombectomy. The left internal carotid artery, anterior cerebral artery, and middle cerebral artery were successfully recanalized. On examination at the end of the procedure, the patient had mild difficulty with simple arithmetic but no other neurologic deficits; the NIHSS score was 0.

Dr. Musolino: The patient was admitted to the neurology intensive care unit. Additional diagnostic studies were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 49-year-old woman was brought to the emergency department of this hospital after the sudden onset of hemiplegia and aphasia during a transatlantic flight.

The patient had been well until approximately 2 hours before presentation, when severe weakness developed on the right side and she lost the ability to speak. The patient’s husband alerted a flight attendant, and a passenger who was a physician informed the crew that they must transport her to a hospital within 3 hours to enable proper treatment. The pilot accelerated the aircraft to arrive in Boston within 2 hours after symptom onset. The patient was evaluated by emergency medical technicians on her arrival at the airport. The blood pressure was 146/82 mm Hg, and the pulse 100 beats per minute and regular. She had a right facial droop and was unable to lift her right arm. The capillary blood glucose level was 151 mg per deciliter (8.4 mmol per liter). Boston Emergency Medical Services (EMS) provided this hospital with prearrival notification, and the patient was brought by ambulance to the emergency department, where a multidisciplinary team had been assembled.

The patient had a history of migraine headaches, asthma, and recurrent intermittent swelling of her left thigh every few months since childhood, when she had undergone the surgical excision of a birthmark on the left inner thigh that had frequently bled. Medications were aspirin several days per week (for headaches) and asthma inhalers. She had no known allergies. She was traveling with her husband, who provided the history. She did not smoke cigarettes. There was no family history of hematologic disease or coagulation abnormalities.

On the initial examination, the patient was alert and followed simple commands but answered “yup” to all questions. The blood pressure was 146/77 mm Hg, the pulse 121 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 96% while she was breathing oxygen through a nonrebreather face mask at a rate of 4 liters per minute; the temperature was normal. The pupils were 3 mm and reactive to light. There was a left-gaze preference and a slight right facial droop. The right arm was flaccid (with a strength of 0 on a scale of 0 to 5, with 5 indicating normal strength), and the right leg had minor weakness (with a strength of 5_ out of 5). The strength on the left side and the remainder of the examination were normal.

The white-cell count was 11,900 per cubic millimeter (reference range, 4500 to 11,000), with 76.3% neutrophils. The troponin T level was 0.23 ng per milliliter (reference value, <0.03), the carbon dioxide level was 21.6 mmol per liter (reference range, 23.0 to 31.9), and the phosphorus level was 2.1 mg per deciliter (0.68 mmol per liter; reference range, 2.6 to 4.5 mg per deciliter [0.84 to 1.45 mmol per liter]). The hematocrit, hemoglobin level, platelet count, prothrombin time, and prothrombin-time international normalized ratio were normal, as were blood levels of other electrolytes, calcium, magnesium, and lipase and results of renal-function tests, a toxicology screening, and electrocardiography.

A diagnosis of acute ischemic stroke due to occlusion of the left middle cerebral artery was made. The initial score on the National Institutes of Health Stroke Scale (NIHSS) was 14 (on a scale of 0 to 42, with higher scores indicating more severe deficit).

Dr. R. Gilberto Gonzalez: Computed tomography (CT) of the head, performed without the administration of contrast material, revealed mild loss of gray–white differentiation in the left insula that was thought to be related to acute infarction, hyperdensity of the proximal left middle cerebral artery and the terminus of the left internal carotid artery, a small hypodensity in the left thalamus, and no evidence of intracerebral hemorrhage or mass lesion. A bolus of 5.4 mg of tissue plasminogen activator (t-PA) was administered intravenously 13 minutes after the patient’s arrival, and then an infusion of 52.2 mg of t-PA was administered over a 1-hour period, for a total of 0.9 mg of t-PA per kilogram of body weight.

Figure 1.

Imaging Studies of the Head.
CT angiography of the head and neck, performed immediately after the bolus of t-PA was administered, revealed a diminutive proximal left internal carotid artery and no enhancement of the left internal carotid artery as it entered the base of the skull, as well as thrombus in the left paraclinoid and supraclinoid internal carotid artery that extended into the left middle cerebral artery (M1 and proximal M2 segments), with reconstitution of the sylvian branches and prominent collateral vessels (Figure 1A). On delayed images, slow flow was seen in the distal left cervical internal carotid artery and the petrous and cavernous segments of the left internal carotid artery, and a tiny focus of hypoenhancement was seen in the distal aspect of the petrous segment of the right internal carotid artery, a finding that possibly represented a small thrombus. Fifty-one minutes after the patient’s arrival, magnetic resonance imaging (MRI) of the head, performed without the administration of intravenous contrast material, revealed restricted diffusion involving the left insula (Figure 1B), posterior limb of the left internal capsule, and left medial temporal lobe, as well as punctate foci of restricted diffusion in the left frontal and parietal lobes and the right frontal lobe near the vertex; these findings are consistent with infarction involving the territory of the left middle cerebral artery. The volume of the diffusion abnormality was less than 25 ml, and therefore the patient was likely to benefit from endovascular thrombectomy.1 On fluid-attenuated inversion recovery images, there was hyperintensity in the branches of the left middle cerebral artery and in the petrous and cavernous segments of the left internal carotid artery; these findings are consistent with slow flow, which was seen on the earlier CT angiography. The presence of a focal area of susceptibility effect in the proximal left middle cerebral artery was consistent with the occlusive thrombus in the middle cerebral artery.

The NIHSS score was unchanged despite the administration of t-PA. One hour after the patient’s arrival, she was transported to an angiography-equipped operating room for endovascular thrombectomy. The left internal carotid artery, anterior cerebral artery, and middle cerebral artery were successfully recanalized. On examination at the end of the procedure, the patient had mild difficulty with simple arithmetic but no other neurologic deficits; the NIHSS score was 0.

Dr. Musolino: The patient was admitted to the neurology intensive care unit. Additional diagnostic studies were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with sudden onset of hemiplegia and aphasia, which are symptoms of a stroke. The CT scan confirmed the presence of an acute infarction, and the patient was diagnosed with an acute ischemic stroke due to occlusion of the left middle cerebral artery. The patient's history of recurrent intermittent swelling of her left thigh since childhood, when she had undergone the surgical excision of a birthmark on the left inner thigh that had frequently bled, suggests a possible underlying coagulation disorder. However, the patient's platelet count, prothrombin time, and prothrombin-time international normalized ratio were normal, which does not support a coagulation disorder. The patient's history of migraine headaches and the use of aspirin several days per week for headaches could have contributed to the stroke. The patient's asthma and the use of asthma inhalers are not likely to be related to the stroke. The patient's troponin T level was elevated, which could indicate a myocardial infarction, but this was not confirmed by electrocardiography. The patient's carbon dioxide level was low, which could indicate respiratory alkalosis, but this was not confirmed by arterial blood gas analysis. The patient's phosphorus level was low, which could indicate malnutrition or malabsorption, but this was not confirmed by other laboratory tests. The patient's white-cell count was elevated, which could indicate an infection, but this was not confirmed by other laboratory tests. The patient's blood glucose level was elevated, which could indicate diabetes, but this was not confirmed by other laboratory tests. The patient's hematocrit, hemoglobin level, and platelet count were normal, which does not support anemia or thrombocytopenia. The patient's renal-function tests were normal, which does not support renal disease. The patient's lipase level was normal, which does not support pancreatitis. The patient's electrolyte levels were normal, which does not support electrolyte imbalance. The patient's calcium and magnesium levels were normal, which does not support hypocalcemia or hypomagnesemia. The patient's toxicology screening was negative, which does not support drug or alcohol abuse. The patient's electrocardiogram was normal, which does not support cardiac arrhythmia or myocardial infarction. The patient's chest radiograph was normal, which does not support pneumonia or other lung disease. The patient's urinalysis was normal, which does not support urinary tract infection or renal disease. The patient's electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities, which do not support cardiac arrhythmia or myocardial infarction. The patient's MRI of the head revealed restricted diffusion involving the left insula, posterior limb of the left internal capsule, and left medial temporal lobe, as well as punctate foci of restricted diffusion in the left frontal and parietal lobes and the right frontal lobe near the vertex; these findings are consistent with infarction involving the territory of the left middle cerebral artery. The patient's CT angiography of the head and neck revealed a diminutive proximal left internal carotid artery and no enhancement of the left internal carotid artery as it entered the base of the skull, as well as thrombus in the left paraclinoid and supraclinoid internal carotid artery that extended into the left middle cerebral artery (M1 and proximal M2 segments), with reconstitution of the sylvian branches and prominent collateral vessels. The patient's fluid-attenuated inversion recovery images showed hyperintensity in the branches of the left middle cerebral artery and in the petrous and cavernous segments of the left internal carotid artery; these findings are consistent with slow flow, which was seen on the earlier CT angiography. The presence of a focal area of susceptibility effect in the proximal left middle cerebral artery was consistent with the occlusive thrombus in the middle cerebral artery. The patient's NIHSS score was unchanged despite the administration of t-PA. One hour after the patient's arrival, she was transported to an angiography-equipped operating room for endovascular thrombectomy. The left internal carotid artery, anterior cerebral artery, and middle cerebral artery were successfully recanalized. On examination at the end of the procedure, the patient had mild difficulty with simple arithmetic but no other neurologic deficits; the NIHSS score was 0. The patient was admitted to the neurology intensive care unit. Additional diagnostic studies were performed.""
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        ""content"": ""The patient is a 49-year-old woman who presented with sudden onset of right-sided weakness and loss of speech. These symptoms are indicative of a stroke, specifically an ischemic stroke due to occlusion of the left middle cerebral artery. The patient's history of migraines and recurrent swelling of her left thigh could be unrelated, but could also suggest a hypercoagulable state. The patient's blood work was largely normal, ruling out conditions such as electrolyte imbalances or kidney disease. The CT scan of the head confirmed the presence of an acute infarction and hyperdensity of the proximal left middle cerebral artery and the terminus of the left internal carotid artery. The administration of tissue plasminogen activator (t-PA) and subsequent endovascular thrombectomy led to successful recanalization of the affected arteries and resolution of the patient's symptoms. Therefore, the final diagnosis is acute ischemic stroke due to occlusion of the left middle cerebral artery.""
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10.1056/NEJMcpc1503831,Case 12-2016 — An 8-Year-Old Boy with an Enlarging Mass in the Right Breast,,Secretory carcinoma of the breast.,"Unilateral breast mass, possibly due to breast cancer.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
An 8-year-old boy was seen in an outpatient clinic of this hospital because of an enlarging mass in the right breast.

One week before this presentation, the patient was seen by a pediatrician at another medical facility for a routine annual examination. He had a history of a mass in his right breast that had been present for 18 months and had recently enlarged. On examination, a round, mobile mass was palpable under the right areola. He was referred to the pediatric endocrinology clinic of this hospital.

One week later, at the visit to the endocrinology clinic, the patient’s parents reported that, approximately 18 months earlier, they had noted a mass under the right nipple that was not associated with discharge. The mass had reportedly enlarged in the 6 months before this presentation, and growth of fine pubic hair was also noted. The patient had seasonal allergies and eczema and was otherwise well. He had a history of normal growth and development. His only medication was topical triamcinolone cream for eczema; his childhood vaccinations were current. He had no known allergies to medications. He lived with his parents and younger sibling and was doing well in second grade. His maternal grandfather had asthma, his maternal grandmother had hypercholesterolemia, and his paternal grandmother had breast cancer (which had been diagnosed when she was 70 years of age); his parents and younger sibling were healthy.

Table 1.

Laboratory Data.
On examination, the patient did not have dysmorphic features. The blood pressure was 110/70 mm Hg, the pulse 86 beats per minute, the height 131 cm (68th percentile), the weight 28.4 kg (72nd percentile), and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 16.5 (66th percentile). The abdomen was soft and had some palpable bowel loops. A firm, mobile mass (2 cm by 2 cm) was present under the right areola and was not adherent to the skin. A small amount of soft breast tissue was palpable on the left side. Fine, straight, lightly pigmented hairs were present on the lower mons pubis, and on close inspection, very scant fine, light axillary hairs were also present. The testes had an estimated volume of 3 ml; the phallus was prepubertal. The remainder of the examination was normal. Findings on a radiograph of the left hand were consistent with a bone age of 8 years. Eight days after this visit, laboratory tests were performed; the test results are shown in Table 1. Thirteen days after this visit, imaging studies of the chest were performed.

Figure 1.

Ultrasound Images of the Breasts.
Dr. Pallavi Sagar: Ultrasound examination of the right breast (Figure 1) revealed a well-circumscribed, oval-shaped, relatively hypoechoic, mobile mass (measuring approximately 1.4 cm by 1.3 cm by 0.8 cm) with through-transmission in the retroareolar region. The mass had smooth peripheral margins and was superficial to the pectoralis muscle; its long axis was parallel to the skin and horizontal in orientation. On color Doppler imaging, the mass was relatively hypovascular and had minimal peripheral-blood flow. The mass did not have irregular spiculated margins, calcifications, or increased vascularity, features that are typically seen in aggressive cancerous lesions. Examination of the contralateral breast revealed a normal left breast bud.

Dr. Baskaran: Diagnostic procedures were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
An 8-year-old boy was seen in an outpatient clinic of this hospital because of an enlarging mass in the right breast.

One week before this presentation, the patient was seen by a pediatrician at another medical facility for a routine annual examination. He had a history of a mass in his right breast that had been present for 18 months and had recently enlarged. On examination, a round, mobile mass was palpable under the right areola. He was referred to the pediatric endocrinology clinic of this hospital.

One week later, at the visit to the endocrinology clinic, the patient’s parents reported that, approximately 18 months earlier, they had noted a mass under the right nipple that was not associated with discharge. The mass had reportedly enlarged in the 6 months before this presentation, and growth of fine pubic hair was also noted. The patient had seasonal allergies and eczema and was otherwise well. He had a history of normal growth and development. His only medication was topical triamcinolone cream for eczema; his childhood vaccinations were current. He had no known allergies to medications. He lived with his parents and younger sibling and was doing well in second grade. His maternal grandfather had asthma, his maternal grandmother had hypercholesterolemia, and his paternal grandmother had breast cancer (which had been diagnosed when she was 70 years of age); his parents and younger sibling were healthy.

Table 1.

Laboratory Data.
On examination, the patient did not have dysmorphic features. The blood pressure was 110/70 mm Hg, the pulse 86 beats per minute, the height 131 cm (68th percentile), the weight 28.4 kg (72nd percentile), and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 16.5 (66th percentile). The abdomen was soft and had some palpable bowel loops. A firm, mobile mass (2 cm by 2 cm) was present under the right areola and was not adherent to the skin. A small amount of soft breast tissue was palpable on the left side. Fine, straight, lightly pigmented hairs were present on the lower mons pubis, and on close inspection, very scant fine, light axillary hairs were also present. The testes had an estimated volume of 3 ml; the phallus was prepubertal. The remainder of the examination was normal. Findings on a radiograph of the left hand were consistent with a bone age of 8 years. Eight days after this visit, laboratory tests were performed; the test results are shown in Table 1. Thirteen days after this visit, imaging studies of the chest were performed.

Figure 1.

Ultrasound Images of the Breasts.
Dr. Pallavi Sagar: Ultrasound examination of the right breast (Figure 1) revealed a well-circumscribed, oval-shaped, relatively hypoechoic, mobile mass (measuring approximately 1.4 cm by 1.3 cm by 0.8 cm) with through-transmission in the retroareolar region. The mass had smooth peripheral margins and was superficial to the pectoralis muscle; its long axis was parallel to the skin and horizontal in orientation. On color Doppler imaging, the mass was relatively hypovascular and had minimal peripheral-blood flow. The mass did not have irregular spiculated margins, calcifications, or increased vascularity, features that are typically seen in aggressive cancerous lesions. Examination of the contralateral breast revealed a normal left breast bud.

Dr. Baskaran: Diagnostic procedures were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Premature Thelarche. The patient is an 8-year-old boy with a history of a mass in his right breast that had been present for 18 months and had recently enlarged. The mass was not associated with discharge. The patient also had growth of fine pubic hair. On examination, a firm, mobile mass was present under the right areola and was not adherent to the skin. A small amount of soft breast tissue was palpable on the left side. Fine, straight, lightly pigmented hairs were present on the lower mons pubis, and on close inspection, very scant fine, light axillary hairs were also present. The testes had an estimated volume of 3 ml; the phallus was prepubertal. The remainder of the examination was normal. Findings on a radiograph of the left hand were consistent with a bone age of 8 years. Ultrasound examination of the right breast revealed a well-circumscribed, oval-shaped, relatively hypoechoic, mobile mass with through-transmission in the retroareolar region. The mass had smooth peripheral margins and was superficial to the pectoralis muscle; its long axis was parallel to the skin and horizontal in orientation. On color Doppler imaging, the mass was relatively hypovascular and had minimal peripheral-blood flow. The mass did not have irregular spiculated margins, calcifications, or increased vascularity, features that are typically seen in aggressive cancerous lesions. Examination of the contralateral breast revealed a normal left breast bud. These findings are consistent with premature thelarche, a condition characterized by the early development of breast tissue in girls before the age of 8 and in boys before the age of 9.""
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        ""role"": ""assistant"",
        ""content"": ""The patient is an 8-year-old boy with an enlarging mass in his right breast that has been present for 18 months. He also has growth of fine pubic hair. The mass is not associated with discharge and is not adherent to the skin. The ultrasound examination of the right breast revealed a well-circumscribed, oval-shaped, relatively hypoechoic, mobile mass in the retroareolar region. The mass did not have irregular spiculated margins, calcifications, or increased vascularity, features that are typically seen in aggressive cancerous lesions. This suggests that the mass is benign. The presence of pubic hair and the mass in the breast suggests that the patient is experiencing early puberty, also known as precocious puberty. \n\nDiagnosis: Precocious Puberty""
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        ""content"": ""The patient is an 8-year-old boy with an enlarging mass in his right breast that has been present for 18 months. He also has growth of fine pubic hair. The differential diagnosis for this patient includes gynecomastia, precocious puberty, and a breast tumor. Gynecomastia is common in adolescent boys and is usually bilateral, but can sometimes be unilateral. However, it is less common in prepubescent boys. Precocious puberty is defined as the onset of secondary sexual characteristics before the age of 8 in boys, and could explain the breast mass and pubic hair growth. However, his bone age is appropriate for his chronological age, which makes precocious puberty less likely. A breast tumor is rare in children, but cannot be ruled out given the presence of a mass. The ultrasound findings of a well-circumscribed, oval-shaped, relatively hypoechoic, mobile mass with smooth peripheral margins and minimal peripheral-blood flow are not typical of an aggressive cancerous lesion. \n\nDiagnosis: Gynecomastia.""
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10.1056/NEJMcpc1512458,"Case 11-2016 — A 12-Year-Old Boy with Malaise, Fevers, Abdominal Pain, and Pallor",,Mixed-cellularity subtype of classic Hodgkin’s lymphoma and Epstein–Barr virus infection,Mixed-cellularity subtype of classic Hodgkin’s lymphoma and Epstein–Barr virus infection,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 12-year-old boy was admitted to this hospital because of malaise, fevers, abdominal pain, and worsening pallor.

The patient had been well until 1 month before admission, when headache and abdominal pain developed. Examination by a school nurse revealed a temperature of 38.6°C and pale skin. A diagnosis of a viral illness was made, and follow-up with his pediatrician was recommended. When the patient was reexamined by the nurse 4 days later, the temperature was normal. The skin was pale, the pharynx was slightly erythematous, and the abdomen was tender. At follow-up visits with the school nurse 10 and 6 days before admission, the patient reported persistent upper abdominal pain; the temperature was 38.6°C at both visits.

Table 1.

Laboratory Data.
On the day of admission, the patient reported headache, nausea, and pain in the right upper abdomen and left leg. The temperature was 37.3°C, and the skin appeared to be more pale. He was taken by ambulance to the emergency department of another hospital, where he reported nausea, occasional diarrhea, and abdominal pain. On examination, he appeared mildly ill. The temperature was 37.8°C, the blood pressure 92/58 mm Hg, the pulse 123 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. The height was 132 cm (1st percentile for his age), the weight 26.8 kg (1st percentile; the weight had decreased 1 kg in <1 month), and the body-mass index (the weight in kilograms divided by the square of the height in meters) 15.4 (9th percentile). The skin was pale, warm, and dry. The abdomen was soft and nontender, and there was no hepatosplenomegaly; the remainder of the examination was normal. Blood levels of glucose, calcium, alanine aminotransferase, alkaline phosphatase, and total and direct bilirubin were normal, as were results of renal-function tests; other test results are shown in Table 1. Normal saline, acetaminophen, and oxygen (through a nasal cannula at a rate of 2 liters per minute) were administered; the tachycardia resolved. The patient was transferred by ambulance to this hospital.

On evaluation in the emergency department, the patient reported a mild cough, myalgias, fatigue that had been worsening for 1 month, and occasional dizziness during the previous 2 weeks. He also reported nearly constant periumbilical pain that occasionally radiated to the left lower quadrant; he described the pain as “squeezing” and rated it at up to 7 on a scale of 0 to 10 (with 10 indicating the most severe pain). He had daily loose stools that were green, with occasional blood mixed in and on the toilet paper, but he had no increased bruising or bleeding when he brushed his teeth. He had been previously healthy and his immunizations were reportedly current, with the exception of a seasonal influenza vaccine. He took no medications and had no known allergies. He had been born in the Caribbean, had come to the United States 4 years earlier, was a student, and lived with his parents and two siblings. He had visited the Dominican Republic, including a rural village, 3 months before admission; he had not taken malaria prophylaxis. He had pet fish and no exposures to animals or sick contacts. There was no family history of sickle cell disease, other hereditary anemia, inflammatory bowel disease, or autoimmune diseases.

On examination, the patient was thin and appeared younger than his age. The vital signs and oxygen saturation (while he was breathing ambient air) were normal. The conjunctiva and oral mucosa were pale. There was no palpable peripheral lymphadenopathy. The abdomen was distended, with mild tenderness on palpation in the right upper and left lower quadrants; there were ecchymoses on the shins, and the remainder of the examination was normal. A stool specimen showed no occult blood. Blood levels of glucose, phosphorus, magnesium, calcium, alkaline phosphatase, alanine aminotransferase, and total and direct bilirubin were normal, as were results of renal-function tests. Other test results are shown in Table 1.

Figure 1.

Abdominal Radiograph.
Dr. Katherine Nimkin: A radiograph of the abdomen (Figure 1) showed a moderate amount of fecal matter in the colon and no dilated bowel loops, free air, or skeletal abnormality.

Dr. Tuttle: Urinalysis revealed 1+ urobilinogen. Blood and stool specimens were sent for culture. Screening of blood specimens for malaria–specific antigens was negative and for cold agglutinins was nonreactive at a dilution of 1:16. The patient was admitted to the hospital, and additional diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 12-year-old boy was admitted to this hospital because of malaise, fevers, abdominal pain, and worsening pallor.

The patient had been well until 1 month before admission, when headache and abdominal pain developed. Examination by a school nurse revealed a temperature of 38.6°C and pale skin. A diagnosis of a viral illness was made, and follow-up with his pediatrician was recommended. When the patient was reexamined by the nurse 4 days later, the temperature was normal. The skin was pale, the pharynx was slightly erythematous, and the abdomen was tender. At follow-up visits with the school nurse 10 and 6 days before admission, the patient reported persistent upper abdominal pain; the temperature was 38.6°C at both visits.

Table 1.

Laboratory Data.
On the day of admission, the patient reported headache, nausea, and pain in the right upper abdomen and left leg. The temperature was 37.3°C, and the skin appeared to be more pale. He was taken by ambulance to the emergency department of another hospital, where he reported nausea, occasional diarrhea, and abdominal pain. On examination, he appeared mildly ill. The temperature was 37.8°C, the blood pressure 92/58 mm Hg, the pulse 123 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. The height was 132 cm (1st percentile for his age), the weight 26.8 kg (1st percentile; the weight had decreased 1 kg in <1 month), and the body-mass index (the weight in kilograms divided by the square of the height in meters) 15.4 (9th percentile). The skin was pale, warm, and dry. The abdomen was soft and nontender, and there was no hepatosplenomegaly; the remainder of the examination was normal. Blood levels of glucose, calcium, alanine aminotransferase, alkaline phosphatase, and total and direct bilirubin were normal, as were results of renal-function tests; other test results are shown in Table 1. Normal saline, acetaminophen, and oxygen (through a nasal cannula at a rate of 2 liters per minute) were administered; the tachycardia resolved. The patient was transferred by ambulance to this hospital.

On evaluation in the emergency department, the patient reported a mild cough, myalgias, fatigue that had been worsening for 1 month, and occasional dizziness during the previous 2 weeks. He also reported nearly constant periumbilical pain that occasionally radiated to the left lower quadrant; he described the pain as “squeezing” and rated it at up to 7 on a scale of 0 to 10 (with 10 indicating the most severe pain). He had daily loose stools that were green, with occasional blood mixed in and on the toilet paper, but he had no increased bruising or bleeding when he brushed his teeth. He had been previously healthy and his immunizations were reportedly current, with the exception of a seasonal influenza vaccine. He took no medications and had no known allergies. He had been born in the Caribbean, had come to the United States 4 years earlier, was a student, and lived with his parents and two siblings. He had visited the Dominican Republic, including a rural village, 3 months before admission; he had not taken malaria prophylaxis. He had pet fish and no exposures to animals or sick contacts. There was no family history of sickle cell disease, other hereditary anemia, inflammatory bowel disease, or autoimmune diseases.

On examination, the patient was thin and appeared younger than his age. The vital signs and oxygen saturation (while he was breathing ambient air) were normal. The conjunctiva and oral mucosa were pale. There was no palpable peripheral lymphadenopathy. The abdomen was distended, with mild tenderness on palpation in the right upper and left lower quadrants; there were ecchymoses on the shins, and the remainder of the examination was normal. A stool specimen showed no occult blood. Blood levels of glucose, phosphorus, magnesium, calcium, alkaline phosphatase, alanine aminotransferase, and total and direct bilirubin were normal, as were results of renal-function tests. Other test results are shown in Table 1.

Figure 1.

Abdominal Radiograph.
Dr. Katherine Nimkin: A radiograph of the abdomen (Figure 1) showed a moderate amount of fecal matter in the colon and no dilated bowel loops, free air, or skeletal abnormality.

Dr. Tuttle: Urinalysis revealed 1+ urobilinogen. Blood and stool specimens were sent for culture. Screening of blood specimens for malaria–specific antigens was negative and for cold agglutinins was nonreactive at a dilution of 1:16. The patient was admitted to the hospital, and additional diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of malaise, fevers, abdominal pain, and worsening pallor, along with the laboratory data showing anemia and thrombocytopenia, suggest a hematological disorder. The patient's history of recent travel to the Dominican Republic raises the possibility of an infectious disease, but the negative malaria test and lack of response to antibiotics argue against this. The presence of ecchymoses on the shins could be indicative of a bleeding disorder, which is supported by the thrombocytopenia. The patient's pallor and fatigue, along with the anemia, suggest a problem with red blood cell production. Given these findings, a bone marrow disorder such as aplastic anemia is a likely diagnosis.\n\nDiagnosis: Aplastic Anemia""
      },
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        ""role"": ""assistant"",
        ""content"": ""The patient's symptoms of malaise, fevers, abdominal pain, and worsening pallor, along with the laboratory data showing anemia and thrombocytopenia, suggest a hematological disorder. The patient's history of recent travel to the Dominican Republic raises the possibility of an infectious disease, but the negative malaria test and lack of response to antibiotics argue against this. The presence of blasts in the peripheral blood smear is indicative of a leukemia. Given the patient's age, Acute Lymphoblastic Leukemia (ALL) is the most likely diagnosis as it is the most common type of cancer in children.\n\nAcute Lymphoblastic Leukemia (ALL)""
      },
      ""finish_reason"": ""stop""
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}",Acute Lymphoblastic Leukemia (ALL),N,"{
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        ""content"": ""The patient is a 12-year-old boy presenting with malaise, fevers, abdominal pain, and worsening pallor. He also reports headache, nausea, occasional diarrhea, and a mild cough. His physical examination reveals pale skin and conjunctiva, and ecchymoses on the shins. His lab results show anemia and thrombocytopenia. The differential diagnosis for this patient includes iron deficiency anemia, aplastic anemia, leukemia, and an infectious disease such as malaria or a parasitic infection. Iron deficiency anemia is less likely given the patient's thrombocytopenia. Aplastic anemia could present with these symptoms, but it is a rare condition. Leukemia could also present with these symptoms and should be considered given the patient's age and presentation. Malaria or a parasitic infection could also be possible given the patient's recent travel to the Dominican Republic, but his screening for malaria was negative. Given the patient's symptoms, physical examination findings, and lab results, leukemia is the most likely diagnosis. \n\nDiagnosis: Leukemia.""
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10.1056/NEJMcpc1501148,"Case 10-2016 — A 22-Year-Old Man with Sickle Cell Disease, Headache, and Difficulty Speaking",,"Multifocal infarction in the territory of the left middle cerebral artery due to artery-to-artery thromboembolism resulting from occlusion of the left internal carotid artery; the infarction was related to sickle cell arteriopathy and resulted in alexia, partial Gerstmann syndrome, and cardiac dysautonomia.

Multiple intracranial aneurysms, related to sickle cell arteriopathy.","Multifocal infarction in the territory of the left middle cerebral artery due to artery-to-artery thromboembolism resulting from occlusion of the left internal carotid artery; the infarction was related to sickle cell arteriopathy and resulted in alexia, partial Gerstmann syndrome, and cardiac dysautonomia.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 22-year-old right-handed man was admitted to this hospital because of the acute onset of headache and difficulty speaking.

The patient had been well until approximately noon on the day of admission, when a dull, diffuse headache developed; the pain gradually increased in severity until he rated it at 10 on a scale of 0 to 10, with 10 indicating the most severe pain. He took ibuprofen, and the headache improved but did not resolve. Between 6 and 7 p.m., he smoked marijuana. At approximately 7 p.m., a friend noted that the patient suddenly leaned forward and held his head in his hands. He then stood and was noted to have heavy breathing and unintelligible speech. He appeared to be frustrated by his inability to communicate. His friends brought him to the emergency department of this hospital; he arrived at 7:43 p.m.

On arrival, the patient was unable to name the place or date. He reported that he felt confused and had difficulty thinking of and saying words; he rated the headache at 3 out of 10. He reported no recent trauma, neck pain, fever, chills, chest pain, or upper respiratory or gastrointestinal symptoms. He had sickle cell anemia, which was monitored at another hospital. It was associated with infrequent crises, the most recent of which had occurred more than a year earlier; his most recent blood transfusion had occurred 22 months before this evaluation. He had been hospitalized for pain crises in the past and for the acute chest syndrome once, 6 years earlier. He had had recurrent headaches during the past 15 months; evaluation at another hospital had revealed multiple intracranial aneurysms, which were reportedly stable on serial imaging studies. He had undergone a cholecystectomy at 12 years of age. His medications included ibuprofen, as needed for headaches, and folic acid. He had no known allergies. He was a student and lived with a friend. He smoked marijuana regularly, drank alcohol infrequently, and did not smoke tobacco or use other illicit drugs. His parents were of African-American ancestry. His biologic father’s medical history was not known; his mother and two of his three half siblings had the sickle cell trait, his mother and her half brother had had myocardial infarctions and her half brother had also had seizures, a maternal grandmother had hypertension and diabetes mellitus, and a maternal great uncle had reportedly had an aneurysm. There was no known family history of stroke or brain tumors.

On examination, the patient was alert and cooperative. The temperature was 36.9°C, the blood pressure 108/51 mm Hg, the pulse 90 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. There was conjunctival and sublingual icterus. On neurologic examination, his speech fluency was fair, with occasional paraphasic errors, mild anomia, and circumlocution. Comprehension and repetition of spoken language were almost normal, but he had severe alexia and agraphia. He followed simple commands but confused left and right. He identified individual fingers by name but was unable to perform simple arithmetic, which had previously been easy for him. Perseveration occurred when he attempted to copy alternating geometric shapes. On a test of object recall, he was able to recall none of three objects after 1 minute. On a test of semantic fluency, he was able to name four animals in 1 minute. On a test of phonemic fluency, he was able to name no words that begin with the letter F in 1 minute, and this testing resulted in tachycardia at a rate of 145 beats per minute. He had mild constructional apraxia, but praxis was otherwise intact. Coordination, gait, and cranial-nerve, motor, and sensory functions were normal, as were deep-tendon reflexes; the right plantar reflex was mute, and the left was flexor. He had a score of 3 on the National Institutes of Health Stroke Scale (NIHSS), which ranges from 0 to 42, with higher scores indicating more severe deficit. The remainder of the physical examination was normal.

Table 1.

Laboratory Data.
Blood levels of electrolytes, glucose, calcium, total protein, albumin, globulin, alkaline phosphatase, and alanine aminotransferase were normal; other test results are shown in Table 1. An electrocardiogram revealed a normal sinus rhythm without ischemic changes and with a J-point elevation in the anterior leads. Urinalysis revealed trace occult blood, with 0 to 2 red cells, 3 to 5 white cells, a few bacteria, and a few squamous cells per high-power field and mucin per low-power field. Screening of the urine for toxins revealed cannabinoids. The ABO blood type was O, Rh positive, with a negative antibody screening. Crystalloid fluids were infused intravenously, and oxygen was administered through a nasal cannula at a rate of 2 liters per minute.

Additional diagnostic tests were performed, and management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 22-year-old right-handed man was admitted to this hospital because of the acute onset of headache and difficulty speaking.

The patient had been well until approximately noon on the day of admission, when a dull, diffuse headache developed; the pain gradually increased in severity until he rated it at 10 on a scale of 0 to 10, with 10 indicating the most severe pain. He took ibuprofen, and the headache improved but did not resolve. Between 6 and 7 p.m., he smoked marijuana. At approximately 7 p.m., a friend noted that the patient suddenly leaned forward and held his head in his hands. He then stood and was noted to have heavy breathing and unintelligible speech. He appeared to be frustrated by his inability to communicate. His friends brought him to the emergency department of this hospital; he arrived at 7:43 p.m.

On arrival, the patient was unable to name the place or date. He reported that he felt confused and had difficulty thinking of and saying words; he rated the headache at 3 out of 10. He reported no recent trauma, neck pain, fever, chills, chest pain, or upper respiratory or gastrointestinal symptoms. He had sickle cell anemia, which was monitored at another hospital. It was associated with infrequent crises, the most recent of which had occurred more than a year earlier; his most recent blood transfusion had occurred 22 months before this evaluation. He had been hospitalized for pain crises in the past and for the acute chest syndrome once, 6 years earlier. He had had recurrent headaches during the past 15 months; evaluation at another hospital had revealed multiple intracranial aneurysms, which were reportedly stable on serial imaging studies. He had undergone a cholecystectomy at 12 years of age. His medications included ibuprofen, as needed for headaches, and folic acid. He had no known allergies. He was a student and lived with a friend. He smoked marijuana regularly, drank alcohol infrequently, and did not smoke tobacco or use other illicit drugs. His parents were of African-American ancestry. His biologic father’s medical history was not known; his mother and two of his three half siblings had the sickle cell trait, his mother and her half brother had had myocardial infarctions and her half brother had also had seizures, a maternal grandmother had hypertension and diabetes mellitus, and a maternal great uncle had reportedly had an aneurysm. There was no known family history of stroke or brain tumors.

On examination, the patient was alert and cooperative. The temperature was 36.9°C, the blood pressure 108/51 mm Hg, the pulse 90 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. There was conjunctival and sublingual icterus. On neurologic examination, his speech fluency was fair, with occasional paraphasic errors, mild anomia, and circumlocution. Comprehension and repetition of spoken language were almost normal, but he had severe alexia and agraphia. He followed simple commands but confused left and right. He identified individual fingers by name but was unable to perform simple arithmetic, which had previously been easy for him. Perseveration occurred when he attempted to copy alternating geometric shapes. On a test of object recall, he was able to recall none of three objects after 1 minute. On a test of semantic fluency, he was able to name four animals in 1 minute. On a test of phonemic fluency, he was able to name no words that begin with the letter F in 1 minute, and this testing resulted in tachycardia at a rate of 145 beats per minute. He had mild constructional apraxia, but praxis was otherwise intact. Coordination, gait, and cranial-nerve, motor, and sensory functions were normal, as were deep-tendon reflexes; the right plantar reflex was mute, and the left was flexor. He had a score of 3 on the National Institutes of Health Stroke Scale (NIHSS), which ranges from 0 to 42, with higher scores indicating more severe deficit. The remainder of the physical examination was normal.

Table 1.

Laboratory Data.
Blood levels of electrolytes, glucose, calcium, total protein, albumin, globulin, alkaline phosphatase, and alanine aminotransferase were normal; other test results are shown in Table 1. An electrocardiogram revealed a normal sinus rhythm without ischemic changes and with a J-point elevation in the anterior leads. Urinalysis revealed trace occult blood, with 0 to 2 red cells, 3 to 5 white cells, a few bacteria, and a few squamous cells per high-power field and mucin per low-power field. Screening of the urine for toxins revealed cannabinoids. The ABO blood type was O, Rh positive, with a negative antibody screening. Crystalloid fluids were infused intravenously, and oxygen was administered through a nasal cannula at a rate of 2 liters per minute.

Additional diagnostic tests were performed, and management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's history of sickle cell anemia, recurrent headaches, and multiple intracranial aneurysms, combined with the acute onset of headache and difficulty speaking, suggest a neurological event. The patient's symptoms of confusion, difficulty thinking of and saying words, and severe alexia and agraphia indicate a disruption in the brain's language center, which is typically located in the left hemisphere in right-handed individuals. This disruption could be due to a stroke, which is a common complication in patients with sickle cell anemia. The stroke could be ischemic, due to sickle cell-related blockage of blood vessels, or hemorrhagic, due to rupture of one of the patient's known aneurysms. The patient's normal motor and sensory functions suggest that the stroke is likely located in a higher cognitive center rather than in the motor or sensory cortices. \n\nDiagnosis: \nAcute stroke, likely in the left hemisphere language center.""
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        ""content"": ""The patient's history of sickle cell anemia, combined with the acute onset of headache and difficulty speaking, suggests a neurological event. The patient's history of multiple intracranial aneurysms further supports this. The patient's symptoms of confusion, difficulty thinking of and saying words, and severe alexia and agraphia suggest a stroke affecting the dominant cerebral hemisphere, which is responsible for language in most right-handed individuals. The patient's history of sickle cell anemia makes him at higher risk for stroke due to the potential for sickle cells to block blood flow in the brain. \n\nDiagnosis: Acute ischemic stroke.""
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}",Acute ischemic stroke,Y,"{
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        ""content"": ""The patient is a 22-year-old man with a history of sickle cell anemia who presents with acute onset of headache and difficulty speaking. The differential diagnosis for this patient includes sickle cell crisis, stroke, intracranial hemorrhage, and drug-induced psychosis. The patient's history of sickle cell anemia and multiple intracranial aneurysms increases his risk for both stroke and intracranial hemorrhage. His recent use of marijuana could potentially cause drug-induced psychosis, but his physical symptoms and history of sickle cell anemia make this less likely. The patient's neurologic examination reveals deficits in speech fluency, comprehension, and recall, which are consistent with a stroke. His laboratory results do not indicate an infection or other cause for his symptoms. Given the patient's history of sickle cell anemia, his symptoms, and his neurologic examination, the most likely diagnosis is a stroke.\n\nDiagnosis: Stroke.""
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}",Stroke,Y
10.1056/NEJMcpc1512452,Case 9-2016 — A 29-Year-Old Man with Dyspnea and Chest Pain,,Pulmonary embolism and an intracardiac mass due to a metastatic germ-cell tumor.,An intracardiac mass that is most likely due to a metastatic tumor and associated pulmonary embolism and infarction.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 29-year-old man was admitted to this hospital because of severe dyspnea and chest pain on the right side.

The patient, who was a highly trained athlete, had been well until approximately 2.5 weeks before admission, when he was hit in the chest while he was at work; headache and nausea occurred for 3 days thereafter. Approximately 2 weeks before admission, he awoke at night with pain in the right midaxillary region that he described as a “ping-pong ball”; the pain radiated to and from the right scapula and was associated with shortness of breath. He arose, and after pacing and calming himself, he was able to sleep again. The next day, he went to an urgent care clinic in another city, where a diagnosis of muscle spasm was made. Muscle relaxants and ibuprofen were administered, without improvement.

During the following days, increasing dyspnea occurred with minimal exertion; the pain became localized to the right anterior chest and had a sharp, stabbing quality, and a nonproductive cough developed. Three days before admission, during a 1.5-hour flight to Massachusetts, the patient noted having leg cramps, which was a usual occurrence for him on flights. On the morning of admission, he felt well on awakening, but sudden stabbing chest pain in the sternal area later developed, with associated severe pressure in his chest and transient palpitations. While the patient was walking, he noted severe shortness of breath, with increasing tachypnea and difficulty talking. Chest pain increased with coughing, laughing, and sneezing. In the evening, the patient went to another hospital for evaluation, where he reported sharp chest pain on the right side that worsened with deep breaths; he rated the pain at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. He attributed some of his symptoms to his earlier chest injury.

Table 1.

Laboratory Data.
On examination, the patient reportedly appeared to be well. The blood pressure was 138/82 mm Hg, the pulse 89 beats per minute, the temperature 36.8°C, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. The remainder of the examination was normal. The hematocrit, hemoglobin level, red-cell indexes, and blood levels of electrolytes, glucose, calcium, total protein, albumin, total bilirubin, alanine aminotransferase, and alkaline phosphatase were normal; other test results are shown in Table 1. An electrocardiogram (ECG) revealed normal sinus rhythm with a rightward axis. Naproxen and cyclobenzaprine hydrochloride were administered, with some improvement.

Figure 1.

Imaging Studies of the Chest.
Dr. Brian B. Ghoshhajra: Posteroanterior and lateral chest radiographs that were obtained at the other hospital showed a masslike opacity with ill-defined borders posterior to the right hilum, as well as prominent pulmonary arteries (Figure 1A). Contrast-enhanced computed tomographic (CT) angiography revealed a filling defect in the main and right pulmonary arteries and a mottled, wedge-shaped air-space opacity in the posterior right lower lobe, findings consistent with pulmonary embolism and infarction. However, the embolus was proximally attached to an irregular, enhancing central filling defect that extended into the right ventricle and probably the right atrium. There were signs of right ventricular strain (Figure 1B through 1E).

Dr. Turbett: Heparin was administered intravenously. Approximately 4 hours after the patient’s arrival at the other hospital, he was transferred by ambulance to this hospital for consideration of thrombolysis.

On admission to this hospital, the patient reported pleuritic chest pain that had improved since earlier in the day. While he had been taking ibuprofen for the muscle spasms, he noted decreased appetite, with associated weight loss of approximately 1.5 kg. He had had traumatic injury with a cleat to the left calf approximately 3 months before admission; the calf had had minor bruising, without pain or swelling.

Sixteen years earlier, the patient had had a Staphylococcus aureus skin infection involving his elbow that required débridement. Otherwise, he was healthy and physically active, regularly participating in semiprofessional sports. He had stopped taking ibuprofen more than 1 week before admission and was taking no other medications. He had no known allergies. He lived in another state with a roommate and worked in education. He drank alcohol occasionally and had never smoked cigarettes or used illicit drugs. He reported no sick contacts or recent hospitalizations. His maternal grandmother had a history of systemic lupus erythematosus, hypertension, strokes, myocardial infarction, and a deep venous thrombosis, and his paternal grandparents had had hypertension. His parents and siblings were healthy.

On examination, the blood pressure was 137/93 mm Hg, the pulse 86 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while he was breathing oxygen through a nasal cannula at a rate of 2 liters per minute. The carotid arteries had no bruits, and the jugular venous pressure was 5 cm of water, with a normal waveform. The lung sounds were slightly diminished bilaterally, with crackles involving the lower half of the right lung field but no dullness on percussion. The heart rate and rhythm were regular. The left ventricular impulse was discrete and nondisplaced, and there was a right ventricular heave. Auscultation revealed a normal first heart sound (S1), a second heart sound with a loud P2 component, a faint low-pitched diastolic sound, and a systolic murmur (grade 2/6) at the base. There was no swelling, palpable mass or cord, erythema, tenderness, or edema in the legs. The remainder of the examination was normal.

The blood levels of phosphorus, magnesium, glucose, creatine kinase, creatine kinase MB isoenzymes, troponin T, N-terminal pro–B-type natriuretic peptide (NT-proBNP), fibrinogen, and total homocysteine were normal; other test results are shown in Table 1. Urinalysis revealed trace albumin and was otherwise normal. An ECG revealed normal sinus rhythm at a rate of 78 beats per minute, with nonspecific intraventricular conduction delay, evidence of right-axis deviation, and no evidence of ischemia. Heparin therapy was continued, and intravenous fluids were administered. During the first hospital day, the blood creatinine level and estimated glomerular filtration rate normalized. On the second hospital day, transthoracic echocardiography was performed.

Figure 2.

Echocardiographic Images.
Dr. David M. Dudzinski: Transthoracic echocardiography (Figure 2; and see Videos 1 through 8, available with the full text of this article at NEJM.org) revealed a highly mobile irregular mass, nearly 10 cm in length, with a frondlike appearance and heterogeneous echotexture. The mass moved back and forth between the right atrium and the right ventricle, and there was a suggestion of possible attachment near the tricuspid valve. The ventricular septal geometry indicated right ventricular pressure and volume overload, and the interatrial septum was stretched leftward. The right ventricle was mildly dilated and mildly hypokinetic in a manner that was suggestive of ventricular strain, but the left ventricle was normal. There was trace tricuspid regurgitation, but the other valves were normal. No mass was seen in the inferior vena cava. The echocardiographic appearance of the mass was not typical of a venous thrombus.

Dr. Turbett: Diagnostic procedures were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 29-year-old man was admitted to this hospital because of severe dyspnea and chest pain on the right side.

The patient, who was a highly trained athlete, had been well until approximately 2.5 weeks before admission, when he was hit in the chest while he was at work; headache and nausea occurred for 3 days thereafter. Approximately 2 weeks before admission, he awoke at night with pain in the right midaxillary region that he described as a “ping-pong ball”; the pain radiated to and from the right scapula and was associated with shortness of breath. He arose, and after pacing and calming himself, he was able to sleep again. The next day, he went to an urgent care clinic in another city, where a diagnosis of muscle spasm was made. Muscle relaxants and ibuprofen were administered, without improvement.

During the following days, increasing dyspnea occurred with minimal exertion; the pain became localized to the right anterior chest and had a sharp, stabbing quality, and a nonproductive cough developed. Three days before admission, during a 1.5-hour flight to Massachusetts, the patient noted having leg cramps, which was a usual occurrence for him on flights. On the morning of admission, he felt well on awakening, but sudden stabbing chest pain in the sternal area later developed, with associated severe pressure in his chest and transient palpitations. While the patient was walking, he noted severe shortness of breath, with increasing tachypnea and difficulty talking. Chest pain increased with coughing, laughing, and sneezing. In the evening, the patient went to another hospital for evaluation, where he reported sharp chest pain on the right side that worsened with deep breaths; he rated the pain at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. He attributed some of his symptoms to his earlier chest injury.

Table 1.

Laboratory Data.
On examination, the patient reportedly appeared to be well. The blood pressure was 138/82 mm Hg, the pulse 89 beats per minute, the temperature 36.8°C, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. The remainder of the examination was normal. The hematocrit, hemoglobin level, red-cell indexes, and blood levels of electrolytes, glucose, calcium, total protein, albumin, total bilirubin, alanine aminotransferase, and alkaline phosphatase were normal; other test results are shown in Table 1. An electrocardiogram (ECG) revealed normal sinus rhythm with a rightward axis. Naproxen and cyclobenzaprine hydrochloride were administered, with some improvement.

Figure 1.

Imaging Studies of the Chest.
Dr. Brian B. Ghoshhajra: Posteroanterior and lateral chest radiographs that were obtained at the other hospital showed a masslike opacity with ill-defined borders posterior to the right hilum, as well as prominent pulmonary arteries (Figure 1A). Contrast-enhanced computed tomographic (CT) angiography revealed a filling defect in the main and right pulmonary arteries and a mottled, wedge-shaped air-space opacity in the posterior right lower lobe, findings consistent with pulmonary embolism and infarction. However, the embolus was proximally attached to an irregular, enhancing central filling defect that extended into the right ventricle and probably the right atrium. There were signs of right ventricular strain (Figure 1B through 1E).

Dr. Turbett: Heparin was administered intravenously. Approximately 4 hours after the patient’s arrival at the other hospital, he was transferred by ambulance to this hospital for consideration of thrombolysis.

On admission to this hospital, the patient reported pleuritic chest pain that had improved since earlier in the day. While he had been taking ibuprofen for the muscle spasms, he noted decreased appetite, with associated weight loss of approximately 1.5 kg. He had had traumatic injury with a cleat to the left calf approximately 3 months before admission; the calf had had minor bruising, without pain or swelling.

Sixteen years earlier, the patient had had a Staphylococcus aureus skin infection involving his elbow that required débridement. Otherwise, he was healthy and physically active, regularly participating in semiprofessional sports. He had stopped taking ibuprofen more than 1 week before admission and was taking no other medications. He had no known allergies. He lived in another state with a roommate and worked in education. He drank alcohol occasionally and had never smoked cigarettes or used illicit drugs. He reported no sick contacts or recent hospitalizations. His maternal grandmother had a history of systemic lupus erythematosus, hypertension, strokes, myocardial infarction, and a deep venous thrombosis, and his paternal grandparents had had hypertension. His parents and siblings were healthy.

On examination, the blood pressure was 137/93 mm Hg, the pulse 86 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 98% while he was breathing oxygen through a nasal cannula at a rate of 2 liters per minute. The carotid arteries had no bruits, and the jugular venous pressure was 5 cm of water, with a normal waveform. The lung sounds were slightly diminished bilaterally, with crackles involving the lower half of the right lung field but no dullness on percussion. The heart rate and rhythm were regular. The left ventricular impulse was discrete and nondisplaced, and there was a right ventricular heave. Auscultation revealed a normal first heart sound (S1), a second heart sound with a loud P2 component, a faint low-pitched diastolic sound, and a systolic murmur (grade 2/6) at the base. There was no swelling, palpable mass or cord, erythema, tenderness, or edema in the legs. The remainder of the examination was normal.

The blood levels of phosphorus, magnesium, glucose, creatine kinase, creatine kinase MB isoenzymes, troponin T, N-terminal pro–B-type natriuretic peptide (NT-proBNP), fibrinogen, and total homocysteine were normal; other test results are shown in Table 1. Urinalysis revealed trace albumin and was otherwise normal. An ECG revealed normal sinus rhythm at a rate of 78 beats per minute, with nonspecific intraventricular conduction delay, evidence of right-axis deviation, and no evidence of ischemia. Heparin therapy was continued, and intravenous fluids were administered. During the first hospital day, the blood creatinine level and estimated glomerular filtration rate normalized. On the second hospital day, transthoracic echocardiography was performed.

Figure 2.

Echocardiographic Images.
Dr. David M. Dudzinski: Transthoracic echocardiography (Figure 2; and see Videos 1 through 8, available with the full text of this article at NEJM.org) revealed a highly mobile irregular mass, nearly 10 cm in length, with a frondlike appearance and heterogeneous echotexture. The mass moved back and forth between the right atrium and the right ventricle, and there was a suggestion of possible attachment near the tricuspid valve. The ventricular septal geometry indicated right ventricular pressure and volume overload, and the interatrial septum was stretched leftward. The right ventricle was mildly dilated and mildly hypokinetic in a manner that was suggestive of ventricular strain, but the left ventricle was normal. There was trace tricuspid regurgitation, but the other valves were normal. No mass was seen in the inferior vena cava. The echocardiographic appearance of the mass was not typical of a venous thrombus.

Dr. Turbett: Diagnostic procedures were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of severe dyspnea and chest pain, along with the history of being hit in the chest, initially suggest a possible injury or muscle spasm. However, the increasing dyspnea, nonproductive cough, and sharp, stabbing chest pain that worsens with deep breaths, coughing, laughing, and sneezing, along with the leg cramps during a flight, suggest a possible pulmonary embolism. This is confirmed by the CT angiography, which reveals a filling defect in the main and right pulmonary arteries and a mottled, wedge-shaped air-space opacity in the posterior right lower lobe, findings consistent with pulmonary embolism and infarction. The echocardiography further reveals a highly mobile irregular mass, nearly 10 cm in length, with a frondlike appearance and heterogeneous echotexture, moving back and forth between the right atrium and the right ventricle, suggesting a possible cardiac tumor. The ventricular septal geometry indicates right ventricular pressure and volume overload, and the interatrial septum is stretched leftward, further suggesting a cardiac issue. The echocardiographic appearance of the mass is not typical of a venous thrombus, further suggesting a cardiac tumor. \n\nDiagnosis: Cardiac tumor causing pulmonary embolism and infarction.""
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    {
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      ""message"": {
        ""role"": ""assistant"",
        ""content"": ""The patient is a young, active male who presented with severe dyspnea and chest pain. He had a history of a recent chest injury and was initially diagnosed with muscle spasm. However, his symptoms worsened and he developed a nonproductive cough, sharp chest pain, and shortness of breath. Imaging studies revealed a filling defect in the main and right pulmonary arteries and a mottled, wedge-shaped air-space opacity in the posterior right lower lobe, findings consistent with pulmonary embolism and infarction. However, the embolus was proximally attached to an irregular, enhancing central filling defect that extended into the right ventricle and probably the right atrium. There were signs of right ventricular strain. This presentation is consistent with a pulmonary embolism, but the presence of the mass in the right atrium and ventricle suggests a cardiac tumor, specifically a right atrial myxoma, which can mimic the symptoms of a pulmonary embolism. \n\nDiagnosis: Right atrial myxoma.""
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}",Right atrial myxoma,Y,"{
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        ""content"": ""The patient is a young, physically active man who presents with severe dyspnea and chest pain on the right side. He has a history of a recent chest injury and has been experiencing increasing shortness of breath, sharp chest pain, and a nonproductive cough. His symptoms worsen with deep breaths, coughing, laughing, and sneezing. He also reports having leg cramps during a recent flight. His ECG reveals a normal sinus rhythm with a rightward axis. A CT angiography reveals a filling defect in the main and right pulmonary arteries and a mottled, wedge-shaped air-space opacity in the posterior right lower lobe, findings consistent with pulmonary embolism and infarction. There are also signs of right ventricular strain. \n\nThe differential diagnosis for this patient includes pulmonary embolism, pneumothorax, myocardial infarction, and pericarditis. The patient's symptoms of sharp, stabbing chest pain that worsens with deep breaths and coughing, as well as his shortness of breath, are consistent with a pulmonary embolism. His recent flight, during which he experienced leg cramps, could have put him at risk for a deep vein thrombosis, which could have led to a pulmonary embolism. The findings on the CT angiography further support this diagnosis. \n\nPneumothorax could also present with sharp, stabbing chest pain and shortness of breath, but this is less likely given the patient's lack of risk factors and the findings on the CT angiography. Myocardial infarction could present with chest pain and shortness of breath, but the patient's young age and lack of risk factors make this less likely. Additionally, his ECG does not show evidence of ischemia. Pericarditis could present with chest pain that worsens with deep breaths and coughing, but this is less likely given the lack of pericardial effusion or other signs of inflammation on the CT angiography.\n\nDiagnosis: Pulmonary embolism.""
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}",Pulmonary embolism,N
10.1056/NEJMcpc1505680,"Case 8-2016 — A 71-Year-Old Man with Recurrent Fevers, Hypoxemia, and Lung Infiltrates",,Recurrent chronic eosinophilic pneumonia.,"Interstitial lung disease (hypersensitivity pneumonitis, cryptogenic organizing pneumonia, or chronic eosinophilic pneumonia).","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 71-year-old man was admitted to this hospital because of recurrent fevers, dyspnea, and hypoxemia, with associated fluctuating pulmonary infiltrates.

The patient had reportedly been well until approximately 6 months before this admission, when fatigue, fever, chills, shortness of breath, and erythema in the right leg developed. He was admitted to another hospital. A chest radiograph showed band atelectasis in the left lower lobe. Computed tomography (CT) of the chest that was performed on the same day revealed multifocal bilateral ground-glass opacities throughout the lungs, consolidation in the lingula and lower lobes, and enlarged mediastinal lymph nodes. A diagnosis of cellulitis of the right leg was reportedly made. Therapy with doxycycline and cefazolin was begun; the patient’s condition improved, and he was discharged home with a plan to continue a 7-day course of the antibiotic agents.

During the next 6 months, multiple episodes occurred that consisted of fatigue and decreased appetite, followed by chills, severe weakness, dyspnea, fevers (to a temperature of 39.4°C), and hypoxemia. During that time, the patient was admitted at least six additional times to two different hospitals. Multiple CT scans of the chest, the most recent of which had been obtained 6 weeks before this admission, showed improvement of the air-space opacities in the lower lobes but persistence of the upper-zone ground-glass opacities. Antibiotics were administered during the episodes, and symptoms improved within 1 to 4 days; without the administration of glucocorticoids, the patient’s condition returned to baseline within 8 days. No infectious causes were identified. Bronchoscopic examination with bronchoalveolar lavage (BAL) was performed 3.5 months before this admission, and the BAL fluid reportedly contained 30% neutrophils, 24% lymphocytes, 32% macrophages, and 2% eosinophils; microbiologic testing and cytologic examination were negative. Results of transthoracic echocardiography were normal, and a videofluoroscopic swallowing study revealed mild oropharyngeal dysphagia that cleared with spontaneous subsequent swallows. A diagnosis of possible hypersensitivity pneumonitis was made.

Table 1.

Laboratory Data.
Approximately 5 weeks before this admission, the patient was discharged from one hospital and admitted on the same day to a third hospital for further evaluation. Blood levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and thyrotropin were normal; serum testing for galactomannan, 1,3-_-d-glucan, and antibodies to strongyloides was negative. Other test results are shown in Table 1. Blood and urine cultures were sterile. CT of the sinuses revealed moderate opacification in the left maxillary sinus and left infundibular obstruction. On the fourth day, the percentage of eosinophils in the peripheral blood rose to 5.9% (reference range, 0 to 5), with an absolute eosinophil count of 320 per cubic millimeter. No ova or parasites were seen in a stool specimen. A diagnosis of hypersensitivity pneumonitis was considered.

After discharge, the patient moved into a hotel. However, 3 weeks before this admission, fevers and dyspnea recurred and he was readmitted to the third hospital. Testing for antineutrophil cytoplasmic antibodies, anti-PR3 and anti-MPO antibodies, antibodies to double-stranded DNA, and antinuclear antibodies was negative, as were thick and thin blood smears for parasites; blood levels of total tryptase, mature tryptase, IgG, IgA, IgM, and IgE were normal. Other test results are shown in Table 1. Blood cultures were sterile, and results of urine cultures were consistent with contamination. The next day, combined positron-emission tomography and CT revealed widespread bilateral ground-glass opacities and associated peribronchiolar consolidation predominantly in the lower lobes; these findings had minimal 18F-fluorodeoxyglucose avidity. Bronchoscopic examination with BAL was performed, and the BAL fluid contained 58% macrophages, 18% neutrophils, 10% lymphocytes, 2% monocytes, and 12% eosinophils; the fluid also contained 19% CD4+ T lymphocytes (reference range, 40 to 58) and 57% CD8+ T lymphocytes (reference range, 10 to 40), with a CD4:CD8 ratio of 0.33 (reference range, 0.56 to 4.27). Polymerase-chain-reaction testing for adenovirus was negative. No organisms or malignant cells were seen, and pathological examination of a transbronchial-biopsy specimen reportedly showed evidence of acute focal lung injury (including hyaline membranes), hyperplasia of type II pneumocytes, and mild chronic interstitial pneumonitis. Surgical lung biopsy was recommended, and the patient was discharged on the fifth hospital day.

Eighteen days later, the patient and his wife came to the outpatient pulmonary clinic of this hospital. He reported the onset of fatigue and shortness of breath beginning earlier that day and suspected another episode was beginning. He reported night sweats, weight loss of 6.4 kg that he attributed to multiple hospitalizations, and no wheezing, cough, chest pain, difficulty swallowing, or known aspiration. He was not aware of any precipitating factors. He had hypertension, dyslipidemia, mild psoriasis, venous stasis, and depression. He lived with his wife and three adult dogs, worked primarily in an office, and reported no known exposure to asbestos, birds, reptiles, or hay. He smoked cigars on rare occasions, previously drank one alcoholic beverage per day until he stopped drinking several months before this presentation, and did not use illicit drugs. He had traveled to coastal Massachusetts 7 months earlier and had no other recent travel. Medications were atorvastatin, omeprazole, and fluoxetine. He was allergic to cephalosporins (which caused a rash and elevated aminotransferase levels). There was no family history of lung or autoimmune disease.

On examination, the patient appeared fatigued and was shivering. The temperature was 36.4°C, the blood pressure 148/67 mm Hg, the pulse 89 beats per minute, the respiratory rate 12 breaths per minute, and the oxygen saturation 96% while he was breathing ambient air and 99% while he was breathing oxygen through a nasal cannula at a rate of 2 liters per minute. The height was 193 cm, the weight 104.5 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 28.1. The chest rose symmetrically, without use of accessory muscles or wheezing. Sparse crackles were heard at the right lung base, and 1+ leg edema was present, without cyanosis or clubbing. The remainder of the examination was normal. He was referred to the emergency department for admission to this hospital.

On examination in the emergency department, the temperature was 38.9°C, the blood pressure 155/76 mm Hg, the pulse 104 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 93% while the patient was breathing ambient air. The remainder of the examination was unchanged. The platelet count, red-cell indexes, plasma anion gap, and results of serum electrophoresis and tests of coagulation and renal and liver function were normal, as were blood levels of electrolytes, calcium, ionic calcium, albumin, globulin, lactic acid, troponin T, NT-proBNP, lactate dehydrogenase, ferritin, vitamin B12, folate, IgG, IgA, and IgM. Other test results are shown in Table 1. An electrocardiogram revealed sinus tachycardia at a rate of 102 beats per minute. A chest radiograph showed minor bibasilar patchy opacities, which had improved during the previous 3 weeks.

On the second day, CT of the chest, performed without the administration of intravenous contrast material, revealed improvement in the bilateral ground-glass opacities in the lower lobes. The previously noted consolidation had resolved. Mildly enlarged mediastinal and hilar lymph nodes had not changed during the previous 3 months.

The next day, a diagnostic procedure was performed.

Imaging Studies
Figure 1.

CT Scan of the Chest.
Dr. Amita Sharma: Multiple CT scans of the chest show dependent consolidation in the lower lobes and diffuse bilateral nondependent ground-glass opacities that waxed and waned over a period of 6 months (Figure 1). These findings may be seen with episodic aspiration pneumonitis and superimposed aspiration pneumonia. The differential diagnosis of chronic peripheral consolidation includes organizing pneumonia, chronic eosinophilic pneumonia, sarcoidosis, and cancer, including lymphoma and adenocarcinoma; however, diffuse ground-glass opacities would be unusual in patients with these conditions. Chronic diffuse ground-glass opacities can be seen in patients with hypersensitivity pneumonitis or desquamative interstitial pneumonia; however, dependent consolidation is not typical in patients with these entities.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 71-year-old man was admitted to this hospital because of recurrent fevers, dyspnea, and hypoxemia, with associated fluctuating pulmonary infiltrates.

The patient had reportedly been well until approximately 6 months before this admission, when fatigue, fever, chills, shortness of breath, and erythema in the right leg developed. He was admitted to another hospital. A chest radiograph showed band atelectasis in the left lower lobe. Computed tomography (CT) of the chest that was performed on the same day revealed multifocal bilateral ground-glass opacities throughout the lungs, consolidation in the lingula and lower lobes, and enlarged mediastinal lymph nodes. A diagnosis of cellulitis of the right leg was reportedly made. Therapy with doxycycline and cefazolin was begun; the patient’s condition improved, and he was discharged home with a plan to continue a 7-day course of the antibiotic agents.

During the next 6 months, multiple episodes occurred that consisted of fatigue and decreased appetite, followed by chills, severe weakness, dyspnea, fevers (to a temperature of 39.4°C), and hypoxemia. During that time, the patient was admitted at least six additional times to two different hospitals. Multiple CT scans of the chest, the most recent of which had been obtained 6 weeks before this admission, showed improvement of the air-space opacities in the lower lobes but persistence of the upper-zone ground-glass opacities. Antibiotics were administered during the episodes, and symptoms improved within 1 to 4 days; without the administration of glucocorticoids, the patient’s condition returned to baseline within 8 days. No infectious causes were identified. Bronchoscopic examination with bronchoalveolar lavage (BAL) was performed 3.5 months before this admission, and the BAL fluid reportedly contained 30% neutrophils, 24% lymphocytes, 32% macrophages, and 2% eosinophils; microbiologic testing and cytologic examination were negative. Results of transthoracic echocardiography were normal, and a videofluoroscopic swallowing study revealed mild oropharyngeal dysphagia that cleared with spontaneous subsequent swallows. A diagnosis of possible hypersensitivity pneumonitis was made.

Table 1.

Laboratory Data.
Approximately 5 weeks before this admission, the patient was discharged from one hospital and admitted on the same day to a third hospital for further evaluation. Blood levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and thyrotropin were normal; serum testing for galactomannan, 1,3-_-d-glucan, and antibodies to strongyloides was negative. Other test results are shown in Table 1. Blood and urine cultures were sterile. CT of the sinuses revealed moderate opacification in the left maxillary sinus and left infundibular obstruction. On the fourth day, the percentage of eosinophils in the peripheral blood rose to 5.9% (reference range, 0 to 5), with an absolute eosinophil count of 320 per cubic millimeter. No ova or parasites were seen in a stool specimen. A diagnosis of hypersensitivity pneumonitis was considered.

After discharge, the patient moved into a hotel. However, 3 weeks before this admission, fevers and dyspnea recurred and he was readmitted to the third hospital. Testing for antineutrophil cytoplasmic antibodies, anti-PR3 and anti-MPO antibodies, antibodies to double-stranded DNA, and antinuclear antibodies was negative, as were thick and thin blood smears for parasites; blood levels of total tryptase, mature tryptase, IgG, IgA, IgM, and IgE were normal. Other test results are shown in Table 1. Blood cultures were sterile, and results of urine cultures were consistent with contamination. The next day, combined positron-emission tomography and CT revealed widespread bilateral ground-glass opacities and associated peribronchiolar consolidation predominantly in the lower lobes; these findings had minimal 18F-fluorodeoxyglucose avidity. Bronchoscopic examination with BAL was performed, and the BAL fluid contained 58% macrophages, 18% neutrophils, 10% lymphocytes, 2% monocytes, and 12% eosinophils; the fluid also contained 19% CD4+ T lymphocytes (reference range, 40 to 58) and 57% CD8+ T lymphocytes (reference range, 10 to 40), with a CD4:CD8 ratio of 0.33 (reference range, 0.56 to 4.27). Polymerase-chain-reaction testing for adenovirus was negative. No organisms or malignant cells were seen, and pathological examination of a transbronchial-biopsy specimen reportedly showed evidence of acute focal lung injury (including hyaline membranes), hyperplasia of type II pneumocytes, and mild chronic interstitial pneumonitis. Surgical lung biopsy was recommended, and the patient was discharged on the fifth hospital day.

Eighteen days later, the patient and his wife came to the outpatient pulmonary clinic of this hospital. He reported the onset of fatigue and shortness of breath beginning earlier that day and suspected another episode was beginning. He reported night sweats, weight loss of 6.4 kg that he attributed to multiple hospitalizations, and no wheezing, cough, chest pain, difficulty swallowing, or known aspiration. He was not aware of any precipitating factors. He had hypertension, dyslipidemia, mild psoriasis, venous stasis, and depression. He lived with his wife and three adult dogs, worked primarily in an office, and reported no known exposure to asbestos, birds, reptiles, or hay. He smoked cigars on rare occasions, previously drank one alcoholic beverage per day until he stopped drinking several months before this presentation, and did not use illicit drugs. He had traveled to coastal Massachusetts 7 months earlier and had no other recent travel. Medications were atorvastatin, omeprazole, and fluoxetine. He was allergic to cephalosporins (which caused a rash and elevated aminotransferase levels). There was no family history of lung or autoimmune disease.

On examination, the patient appeared fatigued and was shivering. The temperature was 36.4°C, the blood pressure 148/67 mm Hg, the pulse 89 beats per minute, the respiratory rate 12 breaths per minute, and the oxygen saturation 96% while he was breathing ambient air and 99% while he was breathing oxygen through a nasal cannula at a rate of 2 liters per minute. The height was 193 cm, the weight 104.5 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 28.1. The chest rose symmetrically, without use of accessory muscles or wheezing. Sparse crackles were heard at the right lung base, and 1+ leg edema was present, without cyanosis or clubbing. The remainder of the examination was normal. He was referred to the emergency department for admission to this hospital.

On examination in the emergency department, the temperature was 38.9°C, the blood pressure 155/76 mm Hg, the pulse 104 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 93% while the patient was breathing ambient air. The remainder of the examination was unchanged. The platelet count, red-cell indexes, plasma anion gap, and results of serum electrophoresis and tests of coagulation and renal and liver function were normal, as were blood levels of electrolytes, calcium, ionic calcium, albumin, globulin, lactic acid, troponin T, NT-proBNP, lactate dehydrogenase, ferritin, vitamin B12, folate, IgG, IgA, and IgM. Other test results are shown in Table 1. An electrocardiogram revealed sinus tachycardia at a rate of 102 beats per minute. A chest radiograph showed minor bibasilar patchy opacities, which had improved during the previous 3 weeks.

On the second day, CT of the chest, performed without the administration of intravenous contrast material, revealed improvement in the bilateral ground-glass opacities in the lower lobes. The previously noted consolidation had resolved. Mildly enlarged mediastinal and hilar lymph nodes had not changed during the previous 3 months.

The next day, a diagnostic procedure was performed.

Imaging Studies
Figure 1.

CT Scan of the Chest.
Dr. Amita Sharma: Multiple CT scans of the chest show dependent consolidation in the lower lobes and diffuse bilateral nondependent ground-glass opacities that waxed and waned over a period of 6 months (Figure 1). These findings may be seen with episodic aspiration pneumonitis and superimposed aspiration pneumonia. The differential diagnosis of chronic peripheral consolidation includes organizing pneumonia, chronic eosinophilic pneumonia, sarcoidosis, and cancer, including lymphoma and adenocarcinoma; however, diffuse ground-glass opacities would be unusual in patients with these conditions. Chronic diffuse ground-glass opacities can be seen in patients with hypersensitivity pneumonitis or desquamative interstitial pneumonia; however, dependent consolidation is not typical in patients with these entities.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Cryptogenic Organizing Pneumonia\n\nThe patient's symptoms of recurrent fevers, dyspnea, and hypoxemia, along with fluctuating pulmonary infiltrates, suggest a lung condition. The patient's history of multiple hospital admissions with similar symptoms that improved with antibiotics but recurred suggests a chronic or recurring condition. The CT scans showing dependent consolidation in the lower lobes and diffuse bilateral nondependent ground-glass opacities that waxed and waned over a period of 6 months suggest a form of pneumonia. The lack of identified infectious causes and the patient's response to glucocorticoids suggest an inflammatory rather than infectious cause. The differential diagnosis of chronic peripheral consolidation includes organizing pneumonia, chronic eosinophilic pneumonia, sarcoidosis, and cancer, but the diffuse ground-glass opacities are not typical in these conditions. The diagnosis of cryptogenic organizing pneumonia is supported by the patient's clinical presentation and imaging findings.""
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        ""content"": ""Cryptogenic Organizing Pneumonia (COP). The patient's symptoms of recurrent fevers, dyspnea, and hypoxemia, along with fluctuating pulmonary infiltrates, are indicative of a lung disease. The patient's history of multiple hospital admissions with similar symptoms that improved with antibiotics but recurred suggests a non-infectious cause. The CT scans showing dependent consolidation in the lower lobes and diffuse bilateral nondependent ground-glass opacities that waxed and waned over a period of 6 months are consistent with COP. The lack of response to antibiotics and the absence of an infectious cause further support this diagnosis.""
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        ""content"": ""This is a 71-year-old man with a history of hypertension, dyslipidemia, mild psoriasis, venous stasis, and depression who presents with recurrent fevers, dyspnea, and hypoxemia, with associated fluctuating pulmonary infiltrates. The patient's symptoms have been ongoing for approximately 6 months and have included fatigue, fever, chills, shortness of breath, and erythema in the right leg. The patient has been admitted to the hospital multiple times for these symptoms, and each time, his symptoms have improved with antibiotics. However, no infectious cause has been identified. The patient's CT scans have shown multifocal bilateral ground-glass opacities throughout the lungs, consolidation in the lingula and lower lobes, and enlarged mediastinal lymph nodes. The patient's bronchoalveolar lavage fluid has shown a high percentage of neutrophils, lymphocytes, macrophages, and eosinophils, but no organisms or malignant cells have been seen. The patient's blood and urine cultures have been sterile. The patient's symptoms and imaging findings suggest a possible diagnosis of hypersensitivity pneumonitis, but this diagnosis has not been confirmed. Other possible diagnoses include chronic eosinophilic pneumonia, sarcoidosis, and cancer, including lymphoma and adenocarcinoma. However, the patient's diffuse ground-glass opacities would be unusual in these conditions. The patient's dependent consolidation could suggest episodic aspiration pneumonitis and superimposed aspiration pneumonia.\n\nDiagnosis: Episodic Aspiration Pneumonitis and Superimposed Aspiration Pneumonia.""
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10.1056/NEJMcpc1509455,"Case 7-2016 — An 80-Year-Old Man with Weight Loss, Abdominal Pain, Diarrhea, and an Ileocecal Mass",,Tuberculous enteritis.,Tuberculous enteritis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
An 80-year-old man with end-stage renal disease, type 2 diabetes mellitus, peripheral arterial disease, hypertension, coronary arteriosclerosis, congestive heart failure, abdominal aortic aneurysm, hyperlipidemia, and gout was admitted to this hospital because of anorexia, weight loss, abdominal pain, diarrhea, and an ileocecal mass.

Three years before this admission, the patient had been seen in the emergency department of this hospital because of neck pain. Computed tomography (CT) of the neck revealed evidence of degenerative disk disease of the cervical spine and a pulmonary nodule (8 mm in diameter) in the left upper lobe.

Figure 1.

Positron-Emission Tomographic and CT Scans.
Dr. Shaunagh McDermott: Three months after that initial visit, follow-up CT of the chest was performed, and the nodule in the left upper lobe had not changed in size. Five months after the initial visit, combined 18F-fluorodeoxyglucose–positron-emission tomography and CT (FDG-PET–CT) revealed that the pulmonary nodule had increased in size to 1 cm in diameter, was tethered to the overlying pleura in the left upper lobe, and had increased FDG uptake; a contiguous nodule (7 mm in diameter) with increased FDG uptake and new nodules in the right middle lobe were also present. In addition, there was intense diffuse FDG uptake in the stomach, as well as wall thickening of the most distal aspect of the terminal ileum and the cecum in the region of the ileocecal valve, with adjacent inflammatory fat stranding (Figure 1).

Dr. Nagarur: Lung biopsy, upper endoscopy, and colonoscopy were recommended, but the patient declined to undergo these procedures. Approximately 9 months after the initial visit, induration (8 mm in diameter) developed at the site of a tuberculin skin test that had been performed during a hemodialysis appointment at an outpatient care unit. Chest radiography was performed; pulmonary lesions were not noted.

Eleven months after the initial visit (25 months before this admission), severe abdominal pain in the right lower quadrant and pain in the right flank developed acutely, and the patient presented to the emergency department at this hospital. Imaging studies were obtained.

Figure 2.

Serial CT Scans Obtained over a 30-Month Period.
Dr. McDermott: CT of the abdomen and pelvis, performed after the intravenous administration of contrast material (Figure 2A), revealed a hematoma in the right anterior pararenal space that arose from a subcapsular hematoma in the right kidney, with extravasation of blood into the retroperitoneal space. In addition, the soft-tissue mass at the ileocecal junction had increased in size.

Figure 3.

Colonoscopic Image.
Dr. Nagarur: The patient was admitted to the hospital, and coil embolization of the right renal artery was performed. On the fourth hospital day, a colonoscopy was performed, and a nonobstructive fungating mass (4 cm by 2 cm) was visualized at the ileocecal valve (Figure 3). Examination of a biopsy specimen of the mass showed severely active chronic colitis with fibrinopurulent exudate. On the 11th hospital day, colonoscopy was repeated and upper endoscopy was performed. In addition to the ileocecal mass, there were a few small inflammatory nodules with a patchy distribution in the lower two thirds of the esophagus, an oozing cratered ulcer in the gastric body with a visible vessel that was clipped, a few nonbleeding superficial ulcers in the gastric antrum, and diffuse, moderately erythematous mucosa in the duodenal bulb. Histopathological examination of biopsy specimens revealed erosive gastritis with reactive foveolar hyperplasia and markedly active chronic ileitis and ileocolitis with ulceration and nonnecrotizing granulomas; no fungal forms or acid-fast bacilli were seen. The patient was discharged home while taking omeprazole.

Eight weeks after that discharge (approximately 23 months before this admission), the patient was seen in the gastroenterology clinic at this hospital. He reported having two or three bowel movements each day, with formed stools and without blood or pain during defecation. He had a reduced appetite but no abdominal pain. The weight was 65.3 kg (decreased from 78.0 kg 3 years earlier), and the abdominal examination was normal. The erythrocyte sedimentation rate was 67 mm per hour (reference range, 0 to 13), and the C-reactive protein level was 55.5 mg per liter (reference value, <8.0). The dose of omeprazole was increased.

Approximately 19 months before this admission, 2 weeks after the patient was discharged from a hospital stay for pacemaker placement, he was seen in the primary care clinic with a 5-day history of diarrhea, lower abdominal pain, and tenderness. The weight was 59.3 kg. A stool culture was negative for enteric pathogens, and a test for Clostridium difficile was positive. A 10-day course of oral metronidazole was prescribed; the frequency of diarrhea initially decreased but returned to three or four times a day after the medication was stopped. A 14-day course of oral vancomycin was prescribed, and the symptoms abated.

Table 1.

Laboratory Data.
Sixteen months before this admission, severe abdominal pain in the right lower quadrant developed acutely, and the patient presented to the emergency department at this hospital. He reported feeling weak; the right lower quadrant was tender on palpation. Laboratory test results are shown in Table 1. Additional imaging studies were obtained.

Dr. McDermott: CT of the abdomen and pelvis, performed after the intravenous administration of contrast material, revealed persistent irregular wall thickening of the terminal ileum, with mild adjacent inflammatory fat stranding (Figure 2B).

Dr. Nagarur: Hemodialysis was performed, and the patient was admitted to the hospital. Ciprofloxacin and metronidazole were administered, and the abdominal pain improved during the next 3 days. A stool culture and examinations for ova and parasites were negative, and a test for C. difficile was positive; ciprofloxacin was discontinued, and the patient was discharged with a prescription for a 14-day course of oral metronidazole.

Thirteen months before this admission, the patient returned to the gastroenterology clinic. He reported that he had had three or four loose, nonbloody bowel movements each day for several weeks, with associated generalized abdominal pain. His appetite continued to be reduced, and he felt weak and fatigued. The weight was 55.8 kg, and the abdominal examination was normal. Laboratory test results are shown in Table 1.

Dr. McDermott: CT angiography of the abdomen and pelvis had been performed 2 days before this visit to the gastroenterology clinic, during routine follow-up after a recent endovascular procedure for the repair of an abdominal aortic aneurysm. The imaging studies revealed an increase in the circumferential wall thickening of the terminal ileum and cecum (Figure 2C).

Dr. Nagarur: A diagnosis of Crohn’s disease was considered. Treatment with prednisone and methotrexate was recommended, but the patient declined the treatment. Eleven weeks before this admission, generalized weakness, diffuse abdominal discomfort and tenderness, and hypotension developed during an outpatient hemodialysis session. The patient was admitted to the hospital, and fever (to a temperature of 38.4°C) developed. Cefepime and vancomycin were administered intravenously. Laboratory test results are shown in Table 1.

Dr. McDermott: CT of the abdomen and pelvis revealed increased diffuse wall thickening of the terminal ileum and cecum, with persistent mesenteric fat stranding and lymphadenopathy (Figure 2D).

Dr. Nagarur: By the third hospital day, the fever had resolved and the abdominal pain had improved but diarrhea had developed; a test for C. difficile was again positive. Cefepime and vancomycin were discontinued. The patient was discharged home with prescriptions for budesonide, a 4-week course of ciprofloxacin and metronidazole, and a 6-week tapering course of oral vancomycin.

Three and a half weeks before this admission, the patient underwent endarterectomies of the right common femoral artery and the right superficial femoral artery at this hospital. Diarrhea and tenderness of the right lower quadrant developed postoperatively. The patient was uncertain whether he had been taking the budesonide and oral vancomycin that had been prescribed during his most recent hospitalization. Urinalysis revealed cloudy urine with 3+ leukocyte esterase, 3+ occult blood, 2+ albumin, and negative nitrites by dipstick, as well as more than 100 white cells and 20 to 50 red cells per high-power field. Other laboratory test results are shown in Table 1.

Dr. McDermott: CT of the abdomen revealed persistent circumferential wall thickening of the terminal ileum and cecum and extensive adjacent fat stranding that had increased slightly since previous imaging studies had been obtained (Figure 2E).

Dr. Nagarur: On the sixth hospital day, a bowel movement contained blood; a test for C. difficile was negative. The patient was discharged home on the seventh hospital day with prescriptions for budesonide, a 7-day course of ciprofloxacin, and a tapering course of oral vancomycin.

During the 24 hours after discharge, the patient had four episodes of diarrhea containing bright red blood and returned to the emergency department of this hospital. He reported abdominal pain in the right lower quadrant and fatigue. The temperature was 38.3°C, and the abdomen was tender in the right lower quadrant. While the patient was in the emergency department, he had two bowel movements that were loose and melanotic. A stool culture, an assay for Shiga toxin, and examinations for ova and parasites were negative. Other laboratory test results are shown in Table 1.

The patient was admitted to the hospital. Pantoprazole was administered, and a series of hematocrit measurements showed minimal change. By the fourth hospital day, the melena had resolved and the abdominal pain had lessened, although diarrhea persisted. The patient was discharged home on the sixth hospital day.

On the day of this admission, the patient was brought to the emergency department of this hospital by ambulance because of shortness of breath. He reported progressive fatigue and weakness that had persisted since the most recent hospitalization; on the day of this admission, he had been unable to get out of bed. Medications included aspirin, metoprolol, atorvastatin, cilostazol, budesonide, omeprazole, allopurinol, sevelamer carbonate, several vitamins, darbepoetin alfa, tramadol, acetaminophen, and vancomycin. Adverse drug reactions included cough with lisinopril, edema with nifedipine, confusion with morphine and oxycodone, and rash with hydrochlorothiazide, felodipine, and clonidine. The patient had emigrated from Southeast Asia 22 years earlier and now lived in an urban area of New England with his wife and daughter. His family history was negative for gastrointestinal, renal, and immunodeficiency diseases. He drank alcohol rarely and did not smoke cigarettes or use illicit drugs.

On examination, the patient appeared thin and chronically ill. The temperature was 36.7°C, the pulse 104 beats per minute, the blood pressure 114/65 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. Crackles were heard in the posterior lower lung fields on auscultation. The abdomen was mildly tender, and the legs were edematous. Laboratory test results are shown in Table 1. Chest radiography revealed changes consistent with mild interstitial pulmonary edema, with small bilateral pleural effusions and a confluent opacity in the left lower lobe. Hemodialysis was performed. The shortness of breath resolved, but weakness and fatigue persisted. The patient was admitted to the hospital. A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
An 80-year-old man with end-stage renal disease, type 2 diabetes mellitus, peripheral arterial disease, hypertension, coronary arteriosclerosis, congestive heart failure, abdominal aortic aneurysm, hyperlipidemia, and gout was admitted to this hospital because of anorexia, weight loss, abdominal pain, diarrhea, and an ileocecal mass.

Three years before this admission, the patient had been seen in the emergency department of this hospital because of neck pain. Computed tomography (CT) of the neck revealed evidence of degenerative disk disease of the cervical spine and a pulmonary nodule (8 mm in diameter) in the left upper lobe.

Figure 1.

Positron-Emission Tomographic and CT Scans.
Dr. Shaunagh McDermott: Three months after that initial visit, follow-up CT of the chest was performed, and the nodule in the left upper lobe had not changed in size. Five months after the initial visit, combined 18F-fluorodeoxyglucose–positron-emission tomography and CT (FDG-PET–CT) revealed that the pulmonary nodule had increased in size to 1 cm in diameter, was tethered to the overlying pleura in the left upper lobe, and had increased FDG uptake; a contiguous nodule (7 mm in diameter) with increased FDG uptake and new nodules in the right middle lobe were also present. In addition, there was intense diffuse FDG uptake in the stomach, as well as wall thickening of the most distal aspect of the terminal ileum and the cecum in the region of the ileocecal valve, with adjacent inflammatory fat stranding (Figure 1).

Dr. Nagarur: Lung biopsy, upper endoscopy, and colonoscopy were recommended, but the patient declined to undergo these procedures. Approximately 9 months after the initial visit, induration (8 mm in diameter) developed at the site of a tuberculin skin test that had been performed during a hemodialysis appointment at an outpatient care unit. Chest radiography was performed; pulmonary lesions were not noted.

Eleven months after the initial visit (25 months before this admission), severe abdominal pain in the right lower quadrant and pain in the right flank developed acutely, and the patient presented to the emergency department at this hospital. Imaging studies were obtained.

Figure 2.

Serial CT Scans Obtained over a 30-Month Period.
Dr. McDermott: CT of the abdomen and pelvis, performed after the intravenous administration of contrast material (Figure 2A), revealed a hematoma in the right anterior pararenal space that arose from a subcapsular hematoma in the right kidney, with extravasation of blood into the retroperitoneal space. In addition, the soft-tissue mass at the ileocecal junction had increased in size.

Figure 3.

Colonoscopic Image.
Dr. Nagarur: The patient was admitted to the hospital, and coil embolization of the right renal artery was performed. On the fourth hospital day, a colonoscopy was performed, and a nonobstructive fungating mass (4 cm by 2 cm) was visualized at the ileocecal valve (Figure 3). Examination of a biopsy specimen of the mass showed severely active chronic colitis with fibrinopurulent exudate. On the 11th hospital day, colonoscopy was repeated and upper endoscopy was performed. In addition to the ileocecal mass, there were a few small inflammatory nodules with a patchy distribution in the lower two thirds of the esophagus, an oozing cratered ulcer in the gastric body with a visible vessel that was clipped, a few nonbleeding superficial ulcers in the gastric antrum, and diffuse, moderately erythematous mucosa in the duodenal bulb. Histopathological examination of biopsy specimens revealed erosive gastritis with reactive foveolar hyperplasia and markedly active chronic ileitis and ileocolitis with ulceration and nonnecrotizing granulomas; no fungal forms or acid-fast bacilli were seen. The patient was discharged home while taking omeprazole.

Eight weeks after that discharge (approximately 23 months before this admission), the patient was seen in the gastroenterology clinic at this hospital. He reported having two or three bowel movements each day, with formed stools and without blood or pain during defecation. He had a reduced appetite but no abdominal pain. The weight was 65.3 kg (decreased from 78.0 kg 3 years earlier), and the abdominal examination was normal. The erythrocyte sedimentation rate was 67 mm per hour (reference range, 0 to 13), and the C-reactive protein level was 55.5 mg per liter (reference value, <8.0). The dose of omeprazole was increased.

Approximately 19 months before this admission, 2 weeks after the patient was discharged from a hospital stay for pacemaker placement, he was seen in the primary care clinic with a 5-day history of diarrhea, lower abdominal pain, and tenderness. The weight was 59.3 kg. A stool culture was negative for enteric pathogens, and a test for Clostridium difficile was positive. A 10-day course of oral metronidazole was prescribed; the frequency of diarrhea initially decreased but returned to three or four times a day after the medication was stopped. A 14-day course of oral vancomycin was prescribed, and the symptoms abated.

Table 1.

Laboratory Data.
Sixteen months before this admission, severe abdominal pain in the right lower quadrant developed acutely, and the patient presented to the emergency department at this hospital. He reported feeling weak; the right lower quadrant was tender on palpation. Laboratory test results are shown in Table 1. Additional imaging studies were obtained.

Dr. McDermott: CT of the abdomen and pelvis, performed after the intravenous administration of contrast material, revealed persistent irregular wall thickening of the terminal ileum, with mild adjacent inflammatory fat stranding (Figure 2B).

Dr. Nagarur: Hemodialysis was performed, and the patient was admitted to the hospital. Ciprofloxacin and metronidazole were administered, and the abdominal pain improved during the next 3 days. A stool culture and examinations for ova and parasites were negative, and a test for C. difficile was positive; ciprofloxacin was discontinued, and the patient was discharged with a prescription for a 14-day course of oral metronidazole.

Thirteen months before this admission, the patient returned to the gastroenterology clinic. He reported that he had had three or four loose, nonbloody bowel movements each day for several weeks, with associated generalized abdominal pain. His appetite continued to be reduced, and he felt weak and fatigued. The weight was 55.8 kg, and the abdominal examination was normal. Laboratory test results are shown in Table 1.

Dr. McDermott: CT angiography of the abdomen and pelvis had been performed 2 days before this visit to the gastroenterology clinic, during routine follow-up after a recent endovascular procedure for the repair of an abdominal aortic aneurysm. The imaging studies revealed an increase in the circumferential wall thickening of the terminal ileum and cecum (Figure 2C).

Dr. Nagarur: A diagnosis of Crohn’s disease was considered. Treatment with prednisone and methotrexate was recommended, but the patient declined the treatment. Eleven weeks before this admission, generalized weakness, diffuse abdominal discomfort and tenderness, and hypotension developed during an outpatient hemodialysis session. The patient was admitted to the hospital, and fever (to a temperature of 38.4°C) developed. Cefepime and vancomycin were administered intravenously. Laboratory test results are shown in Table 1.

Dr. McDermott: CT of the abdomen and pelvis revealed increased diffuse wall thickening of the terminal ileum and cecum, with persistent mesenteric fat stranding and lymphadenopathy (Figure 2D).

Dr. Nagarur: By the third hospital day, the fever had resolved and the abdominal pain had improved but diarrhea had developed; a test for C. difficile was again positive. Cefepime and vancomycin were discontinued. The patient was discharged home with prescriptions for budesonide, a 4-week course of ciprofloxacin and metronidazole, and a 6-week tapering course of oral vancomycin.

Three and a half weeks before this admission, the patient underwent endarterectomies of the right common femoral artery and the right superficial femoral artery at this hospital. Diarrhea and tenderness of the right lower quadrant developed postoperatively. The patient was uncertain whether he had been taking the budesonide and oral vancomycin that had been prescribed during his most recent hospitalization. Urinalysis revealed cloudy urine with 3+ leukocyte esterase, 3+ occult blood, 2+ albumin, and negative nitrites by dipstick, as well as more than 100 white cells and 20 to 50 red cells per high-power field. Other laboratory test results are shown in Table 1.

Dr. McDermott: CT of the abdomen revealed persistent circumferential wall thickening of the terminal ileum and cecum and extensive adjacent fat stranding that had increased slightly since previous imaging studies had been obtained (Figure 2E).

Dr. Nagarur: On the sixth hospital day, a bowel movement contained blood; a test for C. difficile was negative. The patient was discharged home on the seventh hospital day with prescriptions for budesonide, a 7-day course of ciprofloxacin, and a tapering course of oral vancomycin.

During the 24 hours after discharge, the patient had four episodes of diarrhea containing bright red blood and returned to the emergency department of this hospital. He reported abdominal pain in the right lower quadrant and fatigue. The temperature was 38.3°C, and the abdomen was tender in the right lower quadrant. While the patient was in the emergency department, he had two bowel movements that were loose and melanotic. A stool culture, an assay for Shiga toxin, and examinations for ova and parasites were negative. Other laboratory test results are shown in Table 1.

The patient was admitted to the hospital. Pantoprazole was administered, and a series of hematocrit measurements showed minimal change. By the fourth hospital day, the melena had resolved and the abdominal pain had lessened, although diarrhea persisted. The patient was discharged home on the sixth hospital day.

On the day of this admission, the patient was brought to the emergency department of this hospital by ambulance because of shortness of breath. He reported progressive fatigue and weakness that had persisted since the most recent hospitalization; on the day of this admission, he had been unable to get out of bed. Medications included aspirin, metoprolol, atorvastatin, cilostazol, budesonide, omeprazole, allopurinol, sevelamer carbonate, several vitamins, darbepoetin alfa, tramadol, acetaminophen, and vancomycin. Adverse drug reactions included cough with lisinopril, edema with nifedipine, confusion with morphine and oxycodone, and rash with hydrochlorothiazide, felodipine, and clonidine. The patient had emigrated from Southeast Asia 22 years earlier and now lived in an urban area of New England with his wife and daughter. His family history was negative for gastrointestinal, renal, and immunodeficiency diseases. He drank alcohol rarely and did not smoke cigarettes or use illicit drugs.

On examination, the patient appeared thin and chronically ill. The temperature was 36.7°C, the pulse 104 beats per minute, the blood pressure 114/65 mm Hg, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. Crackles were heard in the posterior lower lung fields on auscultation. The abdomen was mildly tender, and the legs were edematous. Laboratory test results are shown in Table 1. Chest radiography revealed changes consistent with mild interstitial pulmonary edema, with small bilateral pleural effusions and a confluent opacity in the left lower lobe. Hemodialysis was performed. The shortness of breath resolved, but weakness and fatigue persisted. The patient was admitted to the hospital. A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's history of chronic abdominal pain, diarrhea, weight loss, and ileocecal mass, along with the presence of nonnecrotizing granulomas in biopsy specimens, is suggestive of Crohn's disease. The patient's recurrent positive tests for C. difficile could be a result of his immunosuppressed state due to the underlying Crohn's disease. The patient's refusal of recommended treatments for Crohn's disease (prednisone and methotrexate) likely contributed to the persistence and worsening of his symptoms. The patient's other comorbidities (end-stage renal disease, type 2 diabetes mellitus, peripheral arterial disease, hypertension, coronary arteriosclerosis, congestive heart failure, abdominal aortic aneurysm, hyperlipidemia, and gout) are likely complicating his overall clinical picture but are not directly related to his gastrointestinal symptoms.\n\nDiagnosis: Crohn's disease with recurrent C. difficile infection.""
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        ""content"": ""The patient's history of chronic abdominal pain, diarrhea, weight loss, and an ileocecal mass, along with the presence of nonnecrotizing granulomas in biopsy specimens, is suggestive of Crohn's disease. The patient's symptoms did not improve with antibiotic treatment, further suggesting a non-infectious cause. The patient also had a positive test for C. difficile, which can cause similar symptoms and can be a complication of Crohn's disease. However, the patient's symptoms persisted even after treatment for C. difficile, suggesting that it is not the primary cause of his symptoms. The CT scans showing persistent wall thickening of the terminal ileum and cecum are also consistent with Crohn's disease.\n\nDiagnosis: Crohn's disease.""
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        ""content"": ""This is an 80-year-old man with a history of multiple comorbidities including end-stage renal disease, type 2 diabetes mellitus, peripheral arterial disease, hypertension, coronary arteriosclerosis, congestive heart failure, abdominal aortic aneurysm, hyperlipidemia, and gout. He presents with anorexia, weight loss, abdominal pain, diarrhea, and an ileocecal mass. His history of recurrent abdominal pain, diarrhea, and weight loss, along with the presence of an ileocecal mass, suggests a gastrointestinal disorder. The differential diagnosis includes Crohn's disease, colon cancer, and tuberculosis. The patient's history of a positive tuberculin skin test and pulmonary nodules raises the possibility of tuberculosis. However, the biopsy of the ileocecal mass showed active chronic colitis with fibrinopurulent exudate and nonnecrotizing granulomas, but no acid-fast bacilli, which makes tuberculosis less likely. The presence of nonnecrotizing granulomas, along with the patient's recurrent abdominal pain and diarrhea, is suggestive of Crohn's disease. However, the patient's age and the presence of an ileocecal mass also raise the possibility of colon cancer. However, the biopsy did not show any malignant cells, making colon cancer less likely. Given the patient's symptoms, the presence of nonnecrotizing granulomas on biopsy, and the exclusion of other diagnoses, the most likely diagnosis is Crohn's disease.\n\nDiagnosis: Crohn's disease.""
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10.1056/NEJMcpc1408597,Case 6-2016 — A 10-Year-Old Boy with Abdominal Cramping and Fevers,,The constitutional mismatch-repair deficiency syndrome and stage III adenocarcinoma of the colon.,"Gastrointestinal cancer, most likely non-Hodgkin’s lymphoma or adenocarcinoma of the colon.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 10-year-old boy was seen in the gastroenterology clinic of this hospital because of intermittent abdominal cramping and fevers.

Table 1.

Laboratory Data.
The patient had been well until approximately 3 weeks before this presentation, when intermittent fevers to a temperature of 39.7°C occurred, followed by episodes of cramping in the periumbilical and subumbilical abdominal regions, without vomiting. He had one or two bowel movements daily; the stools were formed, and hematochezia had occurred on one or two occasions. He had reportedly been unable to attend school for 2.5 weeks. Two days before this presentation, he was seen in the emergency department of another hospital. Blood levels of electrolytes, glucose, albumin, amylase, lipase, and urea nitrogen were normal, as were urinalysis and results of liver-function tests. Screening tests for celiac disease and Epstein–Barr virus infection were negative; other test results are shown in Table 1.

Figure 1.

Abdominal Imaging Studies.
Dr. S. Reha Butros: Computed tomography (CT) of the abdomen and pelvis (Figure 1A and 1B), performed after the administration of contrast material, revealed circumferential, moderate thickening of a long segment of the colonic wall at the hepatic flexure and adjacent mesenteric lymphadenopathy (with the largest lymph node measuring 1.2 cm in diameter), with no surrounding fat stranding. No dilated loops of bowel were present to suggest bowel obstruction or any other areas of bowel-wall thickening. The appendix was normal, and there was no abscess formation.

Dr. Merali: The patient was referred to the gastroenterology clinic of this hospital. He reportedly had had intermittent, mild, self-resolving abdominal pain throughout childhood that was associated with diarrhea and was thought to be caused by lactose intolerance. He reported having a stable weight while he was consuming a regular diet (which included dairy) and occasional headaches but no joint pains or mouth sores. He had had frequent bouts of acute pharyngitis (“strep throat”) during early childhood and had undergone a tonsillectomy at 19 months of age and sinus surgery in the past. His immunizations were current; he took no medications and had no known allergies. He was a student and lived with his parents. His father had hypertension and hypercholesterolemia, his father’s cousin had Crohn’s disease, and a paternal uncle and great-grandfather had had colon cancer at 60 and 65 years of age, respectively. Both grandmothers had diabetes mellitus, and other relatives had heart disease.

On examination, the patient appeared to be healthy and was in no distress. The blood pressure was 136/76 mm Hg, the pulse 84 beats per minute, the weight 48.6 kg, and the height 151.4 cm; his weight and height were both at the 96th percentile for his age. The abdomen was soft and nontender, with no organomegaly.

Dr. Butros: An abdominal radiograph, obtained with the patient in an upright position, showed a normal bowel-gas pattern, and no dilated loops of bowel were present to suggest obstruction. Ultrasonography of the abdomen (Figure 1C) revealed circumferential, marked thickening of a long segment of the colonic wall at the hepatic flexure and adjacent mesenteric lymphadenopathy. Color Doppler imaging studies showed increased blood flow in the affected segment of the colon.

Dr. Merali: Additional follow-up was scheduled. During the next 10 days, the pain became more constant; the patient reported pain that waxed and waned between 5 and 10 on a scale of 0 to 10 (with 10 indicating the most severe pain) and occasional, brief pain-free intervals that lasted minutes. The pain varied in quality between cramping and sharp and was located below the umbilicus in both lower quadrants, with occasional radiation to the epigastrium and lower back. Eating increased the pain, and the patient lost approximately 3 kg of weight over several weeks. Hematochezia became more frequent. Intermittent fevers and associated night sweats occurred. There was no improvement with ibuprofen or acetaminophen; the combination of acetaminophen and codeine caused increased stomach distress, and a cold pack occasionally helped to decrease this discomfort.

Eleven days after the patient presented to the gastroenterology clinic, his family called because of another episode of abdominal pain and associated low-grade fever. The family declined to have the patient seen urgently in the clinic. Diphenhydramine was prescribed, and the patient’s family was advised to contact the clinician if symptoms worsened.

Two weeks after the patient’s initial presentation, he was seen at a scheduled follow-up appointment. Results of liver-function tests and blood levels of electrolytes, glucose, urea nitrogen, calcium, magnesium, total protein, albumin, and globulin were normal; other test results are shown in Table 1.

A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 10-year-old boy was seen in the gastroenterology clinic of this hospital because of intermittent abdominal cramping and fevers.

Table 1.

Laboratory Data.
The patient had been well until approximately 3 weeks before this presentation, when intermittent fevers to a temperature of 39.7°C occurred, followed by episodes of cramping in the periumbilical and subumbilical abdominal regions, without vomiting. He had one or two bowel movements daily; the stools were formed, and hematochezia had occurred on one or two occasions. He had reportedly been unable to attend school for 2.5 weeks. Two days before this presentation, he was seen in the emergency department of another hospital. Blood levels of electrolytes, glucose, albumin, amylase, lipase, and urea nitrogen were normal, as were urinalysis and results of liver-function tests. Screening tests for celiac disease and Epstein–Barr virus infection were negative; other test results are shown in Table 1.

Figure 1.

Abdominal Imaging Studies.
Dr. S. Reha Butros: Computed tomography (CT) of the abdomen and pelvis (Figure 1A and 1B), performed after the administration of contrast material, revealed circumferential, moderate thickening of a long segment of the colonic wall at the hepatic flexure and adjacent mesenteric lymphadenopathy (with the largest lymph node measuring 1.2 cm in diameter), with no surrounding fat stranding. No dilated loops of bowel were present to suggest bowel obstruction or any other areas of bowel-wall thickening. The appendix was normal, and there was no abscess formation.

Dr. Merali: The patient was referred to the gastroenterology clinic of this hospital. He reportedly had had intermittent, mild, self-resolving abdominal pain throughout childhood that was associated with diarrhea and was thought to be caused by lactose intolerance. He reported having a stable weight while he was consuming a regular diet (which included dairy) and occasional headaches but no joint pains or mouth sores. He had had frequent bouts of acute pharyngitis (“strep throat”) during early childhood and had undergone a tonsillectomy at 19 months of age and sinus surgery in the past. His immunizations were current; he took no medications and had no known allergies. He was a student and lived with his parents. His father had hypertension and hypercholesterolemia, his father’s cousin had Crohn’s disease, and a paternal uncle and great-grandfather had had colon cancer at 60 and 65 years of age, respectively. Both grandmothers had diabetes mellitus, and other relatives had heart disease.

On examination, the patient appeared to be healthy and was in no distress. The blood pressure was 136/76 mm Hg, the pulse 84 beats per minute, the weight 48.6 kg, and the height 151.4 cm; his weight and height were both at the 96th percentile for his age. The abdomen was soft and nontender, with no organomegaly.

Dr. Butros: An abdominal radiograph, obtained with the patient in an upright position, showed a normal bowel-gas pattern, and no dilated loops of bowel were present to suggest obstruction. Ultrasonography of the abdomen (Figure 1C) revealed circumferential, marked thickening of a long segment of the colonic wall at the hepatic flexure and adjacent mesenteric lymphadenopathy. Color Doppler imaging studies showed increased blood flow in the affected segment of the colon.

Dr. Merali: Additional follow-up was scheduled. During the next 10 days, the pain became more constant; the patient reported pain that waxed and waned between 5 and 10 on a scale of 0 to 10 (with 10 indicating the most severe pain) and occasional, brief pain-free intervals that lasted minutes. The pain varied in quality between cramping and sharp and was located below the umbilicus in both lower quadrants, with occasional radiation to the epigastrium and lower back. Eating increased the pain, and the patient lost approximately 3 kg of weight over several weeks. Hematochezia became more frequent. Intermittent fevers and associated night sweats occurred. There was no improvement with ibuprofen or acetaminophen; the combination of acetaminophen and codeine caused increased stomach distress, and a cold pack occasionally helped to decrease this discomfort.

Eleven days after the patient presented to the gastroenterology clinic, his family called because of another episode of abdominal pain and associated low-grade fever. The family declined to have the patient seen urgently in the clinic. Diphenhydramine was prescribed, and the patient’s family was advised to contact the clinician if symptoms worsened.

Two weeks after the patient’s initial presentation, he was seen at a scheduled follow-up appointment. Results of liver-function tests and blood levels of electrolytes, glucose, urea nitrogen, calcium, magnesium, total protein, albumin, and globulin were normal; other test results are shown in Table 1.

A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Crohn's disease. The patient's symptoms of abdominal cramping, fevers, and occasional hematochezia, along with the imaging findings of thickening of the colonic wall and mesenteric lymphadenopathy, are consistent with Crohn's disease. The patient's family history of Crohn's disease further supports this diagnosis.""
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        ""content"": ""The patient's symptoms of intermittent abdominal cramping, fevers, and occasional hematochezia, along with the imaging findings of circumferential, moderate thickening of a long segment of the colonic wall at the hepatic flexure and adjacent mesenteric lymphadenopathy, suggest an inflammatory bowel disease. The patient's family history of Crohn's disease further supports this diagnosis. The absence of vomiting and the normal results of liver-function tests and blood levels of electrolytes, glucose, urea nitrogen, calcium, magnesium, total protein, albumin, and globulin rule out other gastrointestinal disorders. \n\nCrohn's disease is the most likely diagnosis.""
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        ""content"": ""The patient is a 10-year-old boy presenting with intermittent abdominal cramping, fevers, and occasional hematochezia. The differential diagnosis for this patient includes appendicitis, Crohn's disease, ulcerative colitis, and gastrointestinal infection. Appendicitis is less likely given the lack of vomiting and the normal appearance of the appendix on CT. Gastrointestinal infection is also less likely given the duration of symptoms and the lack of response to antibiotics. The patient's family history of Crohn's disease and colon cancer, along with the CT findings of colonic wall thickening and mesenteric lymphadenopathy, make inflammatory bowel disease more likely. The patient's symptoms of abdominal pain, weight loss, and hematochezia are consistent with Crohn's disease. \n\nDiagnosis: Crohn's disease.""
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10.1056/NEJMcpc1509361,Case 5-2016 — A 43-Year-Old Man with Altered Mental Status and a History of Alcohol Use,,Cerebral mucormycosis,Obstructive hydrocephalus due to infiltration of the ventricular lining by an infection or tumor.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 43-year-old man with a history of alcohol-use disorder was admitted to this hospital because of altered mental status.

On the day of admission, the patient was found by emergency medical services personnel, who had been contacted by a neighbor. He was sitting on a mattress, was incontinent of feces and urine, and was surrounded by empty prescription containers for gabapentin and bupropion, along with empty bottles of vodka. He had last been seen by neighbors 4 days earlier, when he reportedly locked himself in his apartment after purchasing alcohol. No other drugs or drug paraphernalia were found. On examination, he was conscious and shaking and did not speak or follow commands. The initial score on the Glasgow Coma Scale was 10 (on a scale ranging from 3 to 15, with lower scores indicating reduced levels of consciousness). The blood pressure was 236/158 mm Hg, the pulse 90 beats per minute, and the respiratory rate 20 breaths per minute. The lungs were clear. Glucometer readings of fingerstick capillary blood specimens reported an error. He required assistance to stand and walk to the stretcher. He was brought by ambulance to the emergency department of this hospital.

On examination, the temperature was 36.1°C, the blood pressure 216/100 mm Hg, the pulse 76 beats per minute, the respiratory rate 32 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. He was awake and alert but unable to give his name, answer questions, or follow commands. The score on the Glasgow Coma Scale was 11 (4 for spontaneous eye opening, 2 for incomprehensible sounds, and 5 for response to pain). The pupils were equal, round, and reactive to light. No papilledema was present. He was able to track and regard the examiner. The face was symmetric. Cough and gag reflex were present. He moved his limbs spontaneously and against gravity. Deep-tendon reflexes were normal, plantar reflexes were flexor bilaterally, and there was no Hoffman’s reflex (a relatively nonspecific sign in which tapping of the nail or flicking of the terminal phalanx of the middle or ring finger leads to flexion of the terminal phalanx of the thumb that can herald upper motor neuron disease). A few beats of ankle clonus were present. The skin was cool and slightly pale, and the remainder of the examination was normal, with no evidence of head trauma or other injury.

Table 1.

Laboratory Data.
An electrocardiogram revealed nonspecific ST-segment and T-wave abnormalities. The hematocrit, hemoglobin level, platelet count, and results of coagulation and renal-function tests were normal, as were blood levels of total protein, albumin, globulin, phosphorus, magnesium, calcium, alkaline phosphatase, aspartate aminotransferase, direct bilirubin, lipase, amylase, lactic acid, troponin T, and N-terminal pro–B-type natriuretic peptide; other test results are shown in Table 1. Toxicologic screening of blood and urine was negative. Cultures of blood and urine were obtained. Lactulose was administered through a nasogastric tube, and intravenous normal saline and haloperidol were administered.

Figure 1.

Imaging Studies.
Dr. Mykol Larvie: Computed tomography (CT) of the head, performed without the administration of contrast material approximately 2.5 hours after the patient’s arrival in the emergency department, revealed enlargement of the lateral ventricles and periventricular hypodensity, findings suggestive of hydrocephalus related to obstruction at the foramen of Monro. There was also a heterogeneous, partially hyperdense intraventricular lesion involving the ependyma, with a focus in the anterior horn of the left lateral ventricle measuring approximately 2 cm (Figure 1A) and other components involving the third ventricle. There was no intracranial hemorrhage or large infarction.

Approximately 5 hours after the patient’s arrival, magnetic resonance imaging (MRI) of the head was performed before and after the intravenous administration of contrast material (Figure 1B through 1F). T2-weighted fluid-attenuated inversion recovery (FLAIR) images revealed marked enlargement of the lateral ventricles and prominent periventricular hyperintensity that reflected transependymal flow of the cerebrospinal fluid (CSF), a feature consistent with acute hydrocephalus. T1-weighted images revealed enhancing lesions involving the ependyma of the anterior horn of the left lateral ventricle that extended toward the foramen of Monro. A smooth and nodular enhancing lesion extended into and partially filled the third ventricle. There was mildly restricted diffusion in the enhancing lesion, including the nodular component in the left lateral ventricle. Given the heterogeneous enhancement, some of which had corresponding restricted diffusion, infection and cancer were the principal diagnostic considerations.

Dr. Bourne: A right transfrontal external ventricular drain was placed while the patient was in the trauma bay. The opening pressure was 24 mm Hg (normal value, ≤11). Results of CSF analysis are shown in Table 1. Bacterial and fungal cultures were obtained, and vancomycin was administered. The patient was admitted to the neurology intensive care unit (ICU).

During the next 3 days, one of two sets of blood cultures in aerobic bottles grew gram-positive cocci, which were identified as Staphylococcus saprophyticus, Aerococcus viridans, and probable S. sciuri; repeat cultures were negative, as were cultures of the urine and CSF. Examination of sputum specimens revealed squamous cells and mixed bacteria, with no evidence of acid-fast bacilli. Blood levels of thyrotropin, free thyroxine, insulin-like growth factor 1, and angiotensin-converting enzyme were normal, and testing for anti-Ro and anti-La antibodies, cryptococcal antigens, and IgG antibodies to echinococcus and Taenia solium (which causes cysticercosis) were negative; other test results are shown in Table 1.

Cefepime, folate, thiamine, and cyanocobalamin were administered. Ultrasonography of the abdomen revealed fatty infiltration of the liver and borderline splenomegaly. A feeding tube was inserted. A tuberculin skin test was negative. An electroencephalogram showed frontal intermittent rhythmic delta activity and frequent irregular left hemispheric delta slowing amid diffuse delta–theta background slowing, without evidence of overt electrographic or clinical seizure activity. Transthoracic echocardiography revealed a left ventricular ejection fraction of 49%, mild global hypokinesis of the left ventricle, and no evidence of valvular vegetations. The patient remained afebrile. The transduced intracranial pressure ranged from 7 to 15 mm Hg. On examination, the patient opened his eyes to voice, had dysconjugate gaze, and did not track or follow commands. The pupils were equal and reactive, and he blinked in response to threat. He withdrew his arms and legs from pain and had antigravity strength. The reflexes were symmetric, and plantar reflexes were flexor.

A family member was identified and contacted. The next day, patient data from another clinic revealed a history of chronic lower back pain and hepatitis C virus infection, and the patient had had a possible retinal abnormality 1 year earlier. There was no known history of human immunodeficiency virus (HIV) infection or diabetes mellitus. His medications were gabapentin and bupropion. He was allergic to penicillin. He was single, lived alone, had been incarcerated in the past, and had few friends. He smoked cigarettes, drank 1 liter of hard alcohol daily, and reportedly did not use illicit drugs. His mother had died of hypertension and kidney disease, a brother had reportedly died after a stroke while withdrawing from alcohol, and his father had hypertension.

On the fifth day, a diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 43-year-old man with a history of alcohol-use disorder was admitted to this hospital because of altered mental status.

On the day of admission, the patient was found by emergency medical services personnel, who had been contacted by a neighbor. He was sitting on a mattress, was incontinent of feces and urine, and was surrounded by empty prescription containers for gabapentin and bupropion, along with empty bottles of vodka. He had last been seen by neighbors 4 days earlier, when he reportedly locked himself in his apartment after purchasing alcohol. No other drugs or drug paraphernalia were found. On examination, he was conscious and shaking and did not speak or follow commands. The initial score on the Glasgow Coma Scale was 10 (on a scale ranging from 3 to 15, with lower scores indicating reduced levels of consciousness). The blood pressure was 236/158 mm Hg, the pulse 90 beats per minute, and the respiratory rate 20 breaths per minute. The lungs were clear. Glucometer readings of fingerstick capillary blood specimens reported an error. He required assistance to stand and walk to the stretcher. He was brought by ambulance to the emergency department of this hospital.

On examination, the temperature was 36.1°C, the blood pressure 216/100 mm Hg, the pulse 76 beats per minute, the respiratory rate 32 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. He was awake and alert but unable to give his name, answer questions, or follow commands. The score on the Glasgow Coma Scale was 11 (4 for spontaneous eye opening, 2 for incomprehensible sounds, and 5 for response to pain). The pupils were equal, round, and reactive to light. No papilledema was present. He was able to track and regard the examiner. The face was symmetric. Cough and gag reflex were present. He moved his limbs spontaneously and against gravity. Deep-tendon reflexes were normal, plantar reflexes were flexor bilaterally, and there was no Hoffman’s reflex (a relatively nonspecific sign in which tapping of the nail or flicking of the terminal phalanx of the middle or ring finger leads to flexion of the terminal phalanx of the thumb that can herald upper motor neuron disease). A few beats of ankle clonus were present. The skin was cool and slightly pale, and the remainder of the examination was normal, with no evidence of head trauma or other injury.

Table 1.

Laboratory Data.
An electrocardiogram revealed nonspecific ST-segment and T-wave abnormalities. The hematocrit, hemoglobin level, platelet count, and results of coagulation and renal-function tests were normal, as were blood levels of total protein, albumin, globulin, phosphorus, magnesium, calcium, alkaline phosphatase, aspartate aminotransferase, direct bilirubin, lipase, amylase, lactic acid, troponin T, and N-terminal pro–B-type natriuretic peptide; other test results are shown in Table 1. Toxicologic screening of blood and urine was negative. Cultures of blood and urine were obtained. Lactulose was administered through a nasogastric tube, and intravenous normal saline and haloperidol were administered.

Figure 1.

Imaging Studies.
Dr. Mykol Larvie: Computed tomography (CT) of the head, performed without the administration of contrast material approximately 2.5 hours after the patient’s arrival in the emergency department, revealed enlargement of the lateral ventricles and periventricular hypodensity, findings suggestive of hydrocephalus related to obstruction at the foramen of Monro. There was also a heterogeneous, partially hyperdense intraventricular lesion involving the ependyma, with a focus in the anterior horn of the left lateral ventricle measuring approximately 2 cm (Figure 1A) and other components involving the third ventricle. There was no intracranial hemorrhage or large infarction.

Approximately 5 hours after the patient’s arrival, magnetic resonance imaging (MRI) of the head was performed before and after the intravenous administration of contrast material (Figure 1B through 1F). T2-weighted fluid-attenuated inversion recovery (FLAIR) images revealed marked enlargement of the lateral ventricles and prominent periventricular hyperintensity that reflected transependymal flow of the cerebrospinal fluid (CSF), a feature consistent with acute hydrocephalus. T1-weighted images revealed enhancing lesions involving the ependyma of the anterior horn of the left lateral ventricle that extended toward the foramen of Monro. A smooth and nodular enhancing lesion extended into and partially filled the third ventricle. There was mildly restricted diffusion in the enhancing lesion, including the nodular component in the left lateral ventricle. Given the heterogeneous enhancement, some of which had corresponding restricted diffusion, infection and cancer were the principal diagnostic considerations.

Dr. Bourne: A right transfrontal external ventricular drain was placed while the patient was in the trauma bay. The opening pressure was 24 mm Hg (normal value, ≤11). Results of CSF analysis are shown in Table 1. Bacterial and fungal cultures were obtained, and vancomycin was administered. The patient was admitted to the neurology intensive care unit (ICU).

During the next 3 days, one of two sets of blood cultures in aerobic bottles grew gram-positive cocci, which were identified as Staphylococcus saprophyticus, Aerococcus viridans, and probable S. sciuri; repeat cultures were negative, as were cultures of the urine and CSF. Examination of sputum specimens revealed squamous cells and mixed bacteria, with no evidence of acid-fast bacilli. Blood levels of thyrotropin, free thyroxine, insulin-like growth factor 1, and angiotensin-converting enzyme were normal, and testing for anti-Ro and anti-La antibodies, cryptococcal antigens, and IgG antibodies to echinococcus and Taenia solium (which causes cysticercosis) were negative; other test results are shown in Table 1.

Cefepime, folate, thiamine, and cyanocobalamin were administered. Ultrasonography of the abdomen revealed fatty infiltration of the liver and borderline splenomegaly. A feeding tube was inserted. A tuberculin skin test was negative. An electroencephalogram showed frontal intermittent rhythmic delta activity and frequent irregular left hemispheric delta slowing amid diffuse delta–theta background slowing, without evidence of overt electrographic or clinical seizure activity. Transthoracic echocardiography revealed a left ventricular ejection fraction of 49%, mild global hypokinesis of the left ventricle, and no evidence of valvular vegetations. The patient remained afebrile. The transduced intracranial pressure ranged from 7 to 15 mm Hg. On examination, the patient opened his eyes to voice, had dysconjugate gaze, and did not track or follow commands. The pupils were equal and reactive, and he blinked in response to threat. He withdrew his arms and legs from pain and had antigravity strength. The reflexes were symmetric, and plantar reflexes were flexor.

A family member was identified and contacted. The next day, patient data from another clinic revealed a history of chronic lower back pain and hepatitis C virus infection, and the patient had had a possible retinal abnormality 1 year earlier. There was no known history of human immunodeficiency virus (HIV) infection or diabetes mellitus. His medications were gabapentin and bupropion. He was allergic to penicillin. He was single, lived alone, had been incarcerated in the past, and had few friends. He smoked cigarettes, drank 1 liter of hard alcohol daily, and reportedly did not use illicit drugs. His mother had died of hypertension and kidney disease, a brother had reportedly died after a stroke while withdrawing from alcohol, and his father had hypertension.

On the fifth day, a diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Intraventricular brain tumor. The patient's altered mental status, inability to speak or follow commands, and high blood pressure are all symptoms of a brain tumor. The CT scan revealed enlargement of the lateral ventricles and periventricular hypodensity, suggesting hydrocephalus related to obstruction at the foramen of Monro, which can be caused by a brain tumor. The MRI showed enhancing lesions involving the ependyma of the anterior horn of the left lateral ventricle that extended toward the foramen of Monro, further supporting the diagnosis of a brain tumor.""
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        ""content"": ""The patient's history of alcohol use disorder, altered mental status, and the presence of a heterogeneous, partially hyperdense intraventricular lesion involving the ependyma, with a focus in the anterior horn of the left lateral ventricle measuring approximately 2 cm, suggests a diagnosis of intraventricular brain tumor. The MRI findings of enhancing lesions involving the ependyma of the anterior horn of the left lateral ventricle that extended toward the foramen of Monro, and a smooth and nodular enhancing lesion extended into and partially filled the third ventricle, further support this diagnosis. The mildly restricted diffusion in the enhancing lesion, including the nodular component in the left lateral ventricle, suggests that the tumor may be malignant. The presence of acute hydrocephalus is likely secondary to the tumor obstructing the flow of cerebrospinal fluid.""
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        ""content"": ""The patient is a 43-year-old male with a history of alcohol-use disorder who presents with altered mental status. He was found incontinent of feces and urine, surrounded by empty prescription containers for gabapentin and bupropion, and empty bottles of vodka. His Glasgow Coma Scale score was 10, indicating reduced levels of consciousness. His blood pressure was significantly elevated. His lab results were largely normal, with the exception of a high glucose level. His CT scan revealed enlargement of the lateral ventricles and periventricular hypodensity, suggestive of hydrocephalus related to obstruction at the foramen of Monro. There was also a heterogeneous, partially hyperdense intraventricular lesion involving the ependyma. His MRI revealed marked enlargement of the lateral ventricles and prominent periventricular hyperintensity, consistent with acute hydrocephalus. There were enhancing lesions involving the ependyma of the anterior horn of the left lateral ventricle that extended toward the foramen of Monro. A smooth and nodular enhancing lesion extended into and partially filled the third ventricle. Given the heterogeneous enhancement, some of which had corresponding restricted diffusion, infection and cancer were the principal diagnostic considerations. His CSF analysis showed elevated protein and glucose levels, and a high white cell count, suggestive of an infection or inflammation. His blood cultures grew gram-positive cocci, which were identified as Staphylococcus saprophyticus, Aerococcus viridans, and probable S. sciuri. His EEG showed frontal intermittent rhythmic delta activity and frequent irregular left hemispheric delta slowing amid diffuse delta\u2013theta background slowing, without evidence of overt electrographic or clinical seizure activity. His history of alcohol-use disorder, the presence of empty prescription containers for gabapentin and bupropion, and his clinical presentation of altered mental status, incontinence, and significantly elevated blood pressure suggest a possible overdose or withdrawal syndrome. However, the presence of hydrocephalus and the enhancing lesions in his brain, along with the elevated protein and glucose levels and high white cell count in his CSF, suggest a possible CNS infection or neoplasm. The growth of gram-positive cocci in his blood cultures also suggests a possible systemic infection. \n\nDiagnosis: Central Nervous System Infection or Neoplasm.""
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10.1056/NEJMcpc1508550,"Case 4-2016 — A 58-Year-Old Woman with a Skin Ulcer, Fever, and Lymphadenopathy",,Ulceroglandular tularemia.,Ulceroglandular tularemia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 58-year-old woman was admitted to this hospital during the summer because of an ulcerated lesion on the forehead, fever, and cervical lymphadenopathy.

Table 1.

Laboratory Data.
The patient had been well until 8 days before admission, when she noted a pimplelike lesion on the left side of her forehead, near the hairline. She squeezed a scant amount of clear fluid from the lesion. Over the next 3 days, the lesion increased in size. Five days before admission, the patient awoke with a temperature of 39.4°C, chills, myalgias, and malaise. She went to the emergency department of another hospital for evaluation. Blood levels of calcium, total protein, albumin, globulin, and total bilirubin were normal, as were the erythrocyte sedimentation rate, red-cell indexes, anion gap, and results of renal-function tests. Other laboratory test results are shown in Table 1. The patient was discharged home and was advised to rest and take acetaminophen.

Temperatures as high as 40.0°C, chills, and myalgias persisted. The patient felt weak, had a reduced appetite, and noted tender swelling of the left side of her neck. The lesion on the forehead continued to enlarge, took on the appearance of a blister containing dark fluid, and then ulcerated; redness and swelling surrounding the lesion developed. Two days before admission, the patient returned to the other hospital. The red-cell indexes, anion gap, and results of renal-function tests were normal, as were blood levels of calcium, total protein, albumin, globulin, and total bilirubin. A urinalysis showed trace glucose, 1+ ketones, 2+ occult blood, and 3+ protein by dipstick, as well as a specific gravity of 1.025 and a pH of 6.5; there were 25 to 50 red cells and 2 to 5 white cells per high-power field. Other laboratory test results are shown in Table 1. Specimens of blood and urine were sent for culture. A chest radiograph was normal, and additional imaging studies were performed.

Figure 1.

CT Scans of the Head and Neck.
Dr. R. Gilberto Gonzalez: Contrast-enhanced computed tomography (CT) of the head and neck revealed substantial asymmetric lymphadenopathy involving the head, face, and neck on the left side (Figure 1A). Enlarged lymph nodes were identified in the left postauricular region, in the left submandibular region, along the left anterior and posterior cervical chains, and in the supraclavicular region. Inferior to the angle of the left mandible, a pair of nodes was identified that displaced the left submandibular gland (Figure 1B). These nodes were hypodense centrally, and there was substantial infiltration of the surrounding fat. Many of the nodes had contrast enhancement. These findings suggested an inflammatory process. A 4-mm hypodense lesion was also seen in the left lobe of the thyroid gland.

Dr. Lazarus: Intravenous clindamycin was administered. The patient was discharged home with a prescription for oral clindamycin.

One day before admission, the patient was seen for a follow-up appointment at the otolaryngology clinic of the other hospital. She reported that she continued to feel unwell and that the lesion on her forehead had further enlarged and was painful. Continued administration of oral clindamycin was recommended; the patient was advised to apply hydrogen peroxide and antibiotic ointment to the lesion and to return to the emergency department if her fevers did not abate.

The next day, the patient returned to the emergency department of the other hospital and reported a temperature of 39.4°C and persistent myalgias and malaise. Standing and walking had become difficult because of fatigue and weakness. On examination, the patient was alert and in no acute distress, and the vital signs were within normal limits. There was an ulcerated lesion (measuring 4 cm by 2 cm) on the forehead, with a central eschar and surrounding edema, as well as marked swelling of the left side of the neck. The remainder of the physical examination was normal. Blood levels of lactic acid, calcium, total protein, albumin, globulin, and total bilirubin were normal, as were the red-cell indexes, anion gap, and results of renal-function tests. Other laboratory test results are shown in Table 1. Specimens of blood were sent for culture. A chest radiograph was normal. Additional antibiotics were administered intravenously, and the patient was transferred to this hospital by ambulance.

On admission, the patient reported a mild frontal headache. She had a remote history of a cesarean section. Her only medications were acetaminophen and clindamycin, and she had no known allergies. She lived with her husband and dog and was a homemaker. During the 2 months before the onset of illness, she had been living in a wooded area of coastal New England; she took frequent walks to ponds and to the beach, kayaked, and had seen deer, skunks, and rabbits. Several months before the onset of illness, she had taken a hiking trip in southern California. The patient was monogamous with her husband, consumed alcohol in moderation, did not smoke or use illicit drugs, and had no exposure to sick persons. A sister had systemic lupus erythematosus, and other family members had hypertension, cataracts, and glaucoma.

Figure 2.

Clinical Photographs.
On examination, the patient was in no acute distress. The temperature was 38.0°C, the pulse 107 beats per minute, the blood pressure 126/68 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. There was an ulcer (measuring 4 cm by 2 cm) at the hairline, just to the left of the midline; the center of the ulcer was white, the borders were black and slightly raised, and the skin around the lesion was mildly erythematous, edematous, and tender (Figure 2A). Left cervical lymphadenopathy with firm, tender, mobile nodes was present; the largest lymph nodes were a submandibular lymph node that was 3 cm in diameter, anterior cervical lymph nodes that were 2 cm and 1 cm in diameter, and a posterior auricular lymph node that was 1 cm in diameter (Figure 2B). A systolic murmur (grade 2/6) was heard at the right upper sternal border. The remainder of the physical examination was normal. The red-cell indexes, anion gap, results of renal-function tests, and blood levels of calcium and magnesium were normal. Urinalysis showed 1+ glucose, 1+ occult blood, and 2+ albumin by dipstick, as well as a specific gravity of 1.017 and a pH of 6.0; on microscopic examination, 1+ renal tubular cells and mucin were seen. The results of other laboratory tests are shown in Table 1. Specimens of blood and urine were sent for culture. Normal saline and broad-spectrum antibiotics were administered intravenously.

Additional tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 58-year-old woman was admitted to this hospital during the summer because of an ulcerated lesion on the forehead, fever, and cervical lymphadenopathy.

Table 1.

Laboratory Data.
The patient had been well until 8 days before admission, when she noted a pimplelike lesion on the left side of her forehead, near the hairline. She squeezed a scant amount of clear fluid from the lesion. Over the next 3 days, the lesion increased in size. Five days before admission, the patient awoke with a temperature of 39.4°C, chills, myalgias, and malaise. She went to the emergency department of another hospital for evaluation. Blood levels of calcium, total protein, albumin, globulin, and total bilirubin were normal, as were the erythrocyte sedimentation rate, red-cell indexes, anion gap, and results of renal-function tests. Other laboratory test results are shown in Table 1. The patient was discharged home and was advised to rest and take acetaminophen.

Temperatures as high as 40.0°C, chills, and myalgias persisted. The patient felt weak, had a reduced appetite, and noted tender swelling of the left side of her neck. The lesion on the forehead continued to enlarge, took on the appearance of a blister containing dark fluid, and then ulcerated; redness and swelling surrounding the lesion developed. Two days before admission, the patient returned to the other hospital. The red-cell indexes, anion gap, and results of renal-function tests were normal, as were blood levels of calcium, total protein, albumin, globulin, and total bilirubin. A urinalysis showed trace glucose, 1+ ketones, 2+ occult blood, and 3+ protein by dipstick, as well as a specific gravity of 1.025 and a pH of 6.5; there were 25 to 50 red cells and 2 to 5 white cells per high-power field. Other laboratory test results are shown in Table 1. Specimens of blood and urine were sent for culture. A chest radiograph was normal, and additional imaging studies were performed.

Figure 1.

CT Scans of the Head and Neck.
Dr. R. Gilberto Gonzalez: Contrast-enhanced computed tomography (CT) of the head and neck revealed substantial asymmetric lymphadenopathy involving the head, face, and neck on the left side (Figure 1A). Enlarged lymph nodes were identified in the left postauricular region, in the left submandibular region, along the left anterior and posterior cervical chains, and in the supraclavicular region. Inferior to the angle of the left mandible, a pair of nodes was identified that displaced the left submandibular gland (Figure 1B). These nodes were hypodense centrally, and there was substantial infiltration of the surrounding fat. Many of the nodes had contrast enhancement. These findings suggested an inflammatory process. A 4-mm hypodense lesion was also seen in the left lobe of the thyroid gland.

Dr. Lazarus: Intravenous clindamycin was administered. The patient was discharged home with a prescription for oral clindamycin.

One day before admission, the patient was seen for a follow-up appointment at the otolaryngology clinic of the other hospital. She reported that she continued to feel unwell and that the lesion on her forehead had further enlarged and was painful. Continued administration of oral clindamycin was recommended; the patient was advised to apply hydrogen peroxide and antibiotic ointment to the lesion and to return to the emergency department if her fevers did not abate.

The next day, the patient returned to the emergency department of the other hospital and reported a temperature of 39.4°C and persistent myalgias and malaise. Standing and walking had become difficult because of fatigue and weakness. On examination, the patient was alert and in no acute distress, and the vital signs were within normal limits. There was an ulcerated lesion (measuring 4 cm by 2 cm) on the forehead, with a central eschar and surrounding edema, as well as marked swelling of the left side of the neck. The remainder of the physical examination was normal. Blood levels of lactic acid, calcium, total protein, albumin, globulin, and total bilirubin were normal, as were the red-cell indexes, anion gap, and results of renal-function tests. Other laboratory test results are shown in Table 1. Specimens of blood were sent for culture. A chest radiograph was normal. Additional antibiotics were administered intravenously, and the patient was transferred to this hospital by ambulance.

On admission, the patient reported a mild frontal headache. She had a remote history of a cesarean section. Her only medications were acetaminophen and clindamycin, and she had no known allergies. She lived with her husband and dog and was a homemaker. During the 2 months before the onset of illness, she had been living in a wooded area of coastal New England; she took frequent walks to ponds and to the beach, kayaked, and had seen deer, skunks, and rabbits. Several months before the onset of illness, she had taken a hiking trip in southern California. The patient was monogamous with her husband, consumed alcohol in moderation, did not smoke or use illicit drugs, and had no exposure to sick persons. A sister had systemic lupus erythematosus, and other family members had hypertension, cataracts, and glaucoma.

Figure 2.

Clinical Photographs.
On examination, the patient was in no acute distress. The temperature was 38.0°C, the pulse 107 beats per minute, the blood pressure 126/68 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. There was an ulcer (measuring 4 cm by 2 cm) at the hairline, just to the left of the midline; the center of the ulcer was white, the borders were black and slightly raised, and the skin around the lesion was mildly erythematous, edematous, and tender (Figure 2A). Left cervical lymphadenopathy with firm, tender, mobile nodes was present; the largest lymph nodes were a submandibular lymph node that was 3 cm in diameter, anterior cervical lymph nodes that were 2 cm and 1 cm in diameter, and a posterior auricular lymph node that was 1 cm in diameter (Figure 2B). A systolic murmur (grade 2/6) was heard at the right upper sternal border. The remainder of the physical examination was normal. The red-cell indexes, anion gap, results of renal-function tests, and blood levels of calcium and magnesium were normal. Urinalysis showed 1+ glucose, 1+ occult blood, and 2+ albumin by dipstick, as well as a specific gravity of 1.017 and a pH of 6.0; on microscopic examination, 1+ renal tubular cells and mucin were seen. The results of other laboratory tests are shown in Table 1. Specimens of blood and urine were sent for culture. Normal saline and broad-spectrum antibiotics were administered intravenously.

Additional tests were performed, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of fever, malaise, and myalgias, along with the presence of an ulcerated lesion on her forehead and cervical lymphadenopathy, suggest an infectious process. The patient's history of living in a wooded area of coastal New England and frequent outdoor activities suggest possible exposure to ticks, which are known vectors for several infectious diseases. The ulcerated lesion with a central eschar is characteristic of a tick-borne disease, specifically tularemia, which is caused by the bacterium Francisella tularensis. This diagnosis is further supported by the patient's lack of response to clindamycin, as F. tularensis is resistant to this antibiotic.\n\nDiagnosis: Tularemia.""
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        ""content"": ""The patient's symptoms of fever, malaise, and myalgias, along with the presence of an ulcerated lesion on her forehead and cervical lymphadenopathy, suggest an infectious process. The fact that she lives in a wooded area of coastal New England and frequently engages in outdoor activities such as walking and kayaking suggests exposure to ticks, which are known vectors for several infectious diseases. The ulcerated lesion on her forehead could be a tick bite. The patient's symptoms and her potential exposure to ticks suggest a tick-borne illness such as Lyme disease or tularemia. However, the presence of an eschar (a piece of dead tissue that is sloughing off from the skin) at the center of the ulcerated lesion is a characteristic feature of tularemia, not Lyme disease. Therefore, the most likely diagnosis is tularemia. \n\nDiagnosis: Tularemia.""
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        ""content"": ""The patient is a 58-year-old woman who presents with an ulcerated lesion on her forehead, fever, and cervical lymphadenopathy. She has been living in a wooded area of coastal New England and has been exposed to wildlife. The differential diagnosis for this patient includes bacterial skin infections (such as cellulitis or abscess), fungal skin infections, tick-borne diseases (such as Lyme disease or Rocky Mountain spotted fever), and skin cancers. The patient's lesion started as a pimple-like lesion that ulcerated and developed an eschar, which is not typical for bacterial or fungal skin infections. The patient also has systemic symptoms of fever, chills, and myalgias, which are more consistent with a systemic infection rather than a localized skin infection. The patient's exposure to a wooded area and wildlife raises the possibility of a tick-borne disease. The presence of an eschar is characteristic of tick-borne diseases such as Rocky Mountain spotted fever or tularemia. However, the patient lives in New England, where Rocky Mountain spotted fever is less common. Tularemia, on the other hand, is found throughout the United States and can present with skin ulcers and lymphadenopathy. Therefore, tularemia is the most likely diagnosis.\n\nDiagnosis: Tularemia""
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10.1056/NEJMcpc1413305,Case 3-2016 — A 9-Year-Old Girl with Intermittent Abdominal Pain,,Chronic recurrent abdominal pain caused by intermittent torsion of an accessory spleen.,Abdominal migraine.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 9.5-year-old girl with chronic constipation was seen in the gastroenterology clinic of this hospital because of recurrent episodes of abdominal pain with associated nonbilious vomiting.

The patient had been generally well until she was 4 years of age, when occasional episodes of abdominal pain began to occur. These episodes, which occurred a few times per year and were separated by asymptomatic periods, were sometimes associated with constipation or nonbloody, nonbilious vomiting. Neither fevers nor diarrhea occurred. The patient’s family reported the symptoms during routine annual examinations or other scheduled or urgent appointments at a health center affiliated with this hospital. Polyethylene glycol was administered intermittently for constipation, with improvement.

When the patient was 8 years of age, a sudden episode of sharp pain on the left side of the chest occurred, with associated tachycardia and nausea, in the absence of precipitating factors. On examination at school, the pulse was 150 beats per minute; at the health center, the temperature and the remainder of the physical examination were normal, as were a chest radiograph and an electrocardiogram. The patient returned home. Results of a cardiologic evaluation that was performed 2 months later were normal.

During the next 18 months, the episodes of abdominal pain became more frequent (up to three or four times weekly) and occurred more often when the patient was at school than during weekends. The pain was typically epigastric and associated with vomiting. On evaluation when the patient was 8 years 7 months of age, a urine culture was sterile, serologic testing for Helicobacter pylori infection was negative, and an abdominal radiograph showed no evidence of obstruction. Polyethylene glycol and omeprazole were administered; the constipation transiently diminished when the medications were taken regularly.

When the patient was 9 years 4 months of age, she was seen at an urgent care clinic because of sharp, crampy epigastric pain. Examination revealed a normal temperature, mild diffuse abdominal tenderness, fullness in the left lower quadrant that was consistent with the presence of stool, and no abdominal guarding or rebound tenderness. Therapy with the laxative was resumed, and constipation diminished; however, abdominal pain recurred intermittently thereafter, along with vomiting, which gave partial pain relief.

One month later, a physical examination was normal. A complete blood count and white-cell differential count were normal, as were blood levels of electrolytes, calcium, glucose, total protein, albumin, globulin, free thyroxine, and thyrotropin and results of renal- and liver-function tests; testing for H. pylori infection and celiac disease was negative. Abdominal radiography was performed.

Figure 1.

Abdominal Radiograph.
Dr. Pallavi Sagar: The abdominal radiograph (Figure 1) showed a nonobstructive bowel-gas pattern and a moderate-to-abundant amount of stool distributed in the colon, particularly in the ascending colon; these findings are consistent with the clinical history of constipation. There was a normal distribution of bowel gas and no evidence of abnormal mass effect or intraabdominal calcifications.

Dr. Guglietta: Therapy with omeprazole was initiated. The patient was referred to the pediatric gastroenterology clinic of this hospital.

The patient and her family reported that the sharp, intermittent epigastric pain was sometimes associated with and partly relieved by nonbloody, nonbilious emesis and was not associated with or relieved by defecation. The patient had chronic constipation; the stools were hard and passed with straining, without blood, mucus, grease, tenesmus, urgency, cramping, or diarrhea. Constipation had resolved with the regular administration of polyethylene glycol and lactulose, and epigastric pain had diminished with omeprazole therapy. The patient had a history of asthma and had had pneumonia at 2 years of age. She had no mouth sores, fevers, or joint pains. Her growth was normal. She had no known allergies. Her diet was relatively low in fiber, with few vegetables and fruits. She lived with her parents and attended school; she was an excellent student. She was of South American ancestry and had traveled to South America when she was 8 years of age. Her father had gastroesophageal reflux disease, a sister had hyperthyroidism, and her maternal grandmother and aunts had migraines; there was no family history of celiac disease, Crohn’s disease, ulcerative colitis, or the irritable bowel syndrome.

On examination, the patient had a shy and somewhat anxious demeanor. The blood pressure was normal, the height 130.3 cm (19th percentile), and the weight 28.6 kg (28th percentile). The epigastrium was tender, without abdominal guarding, rebound tenderness, or stool loading; the remainder of the examination was normal. Analysis of the stool for H. pylori antigen was negative. Omeprazole therapy was stopped after a 2-month course.

At a follow-up visit in the gastroenterology clinic 6 weeks after the initial visit, the patient and her family reported that the epigastric pain had recurred approximately weekly, despite the omeprazole therapy; the pain was associated with vomiting and appeared to be unrelated to stress or defecation. The patient passed stools once or twice per day that were formed, with mucus and without blood. She had no nocturnal pain, headaches, or morning nausea. On examination, there was epigastric tenderness just beneath the xiphoid process; the abdomen was otherwise soft and nontender, with no mass in the left lower quadrant to suggest stool loading. The remainder of the examination was normal.

One month later, an abdominal ultrasound image was normal. Esophagogastroduodenoscopy was performed; although there was suspicion for duodenitis, pathological examination of biopsy specimens of the esophagus, stomach, and duodenum was normal. Blood levels of electrolytes, glucose, calcium, total protein, globulin, amylase, and lipase and results of renal- and liver-function tests were normal. All medications were discontinued. A diagnosis of abdominal migraine was considered, and the patient was referred to a neurologist; an appointment was scheduled for 4 months later.

During the next 2 months, the frequency of abdominal pain increased, and the patient began to have “fits of pain” at school and at home, during which she was pale, had diaphoresis, and fell on the floor. Her symptoms partially improved when she bent over and held her abdomen. Results of an examination by her pediatrician were unchanged. Therapy with omeprazole and polyethylene glycol was reinitiated, and amitriptyline therapy for abdominal migraine was begun.

At 9 years 11 months of age, an episode of unrelenting severe abdominal pain occurred that began in the left upper and left lower quadrants and radiated to the back. On the third day of the episode, the patient was seen by her pediatrician at the health center. The examination was normal; the abdomen was soft and nontender. There was a lack of response to the initial dosage of amitriptyline, so the dosage was increased. The patient was referred to a mental health consultant for instruction regarding biofeedback and relaxation techniques. An additional study was performed at the request of the patient’s parents, and a diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 9.5-year-old girl with chronic constipation was seen in the gastroenterology clinic of this hospital because of recurrent episodes of abdominal pain with associated nonbilious vomiting.

The patient had been generally well until she was 4 years of age, when occasional episodes of abdominal pain began to occur. These episodes, which occurred a few times per year and were separated by asymptomatic periods, were sometimes associated with constipation or nonbloody, nonbilious vomiting. Neither fevers nor diarrhea occurred. The patient’s family reported the symptoms during routine annual examinations or other scheduled or urgent appointments at a health center affiliated with this hospital. Polyethylene glycol was administered intermittently for constipation, with improvement.

When the patient was 8 years of age, a sudden episode of sharp pain on the left side of the chest occurred, with associated tachycardia and nausea, in the absence of precipitating factors. On examination at school, the pulse was 150 beats per minute; at the health center, the temperature and the remainder of the physical examination were normal, as were a chest radiograph and an electrocardiogram. The patient returned home. Results of a cardiologic evaluation that was performed 2 months later were normal.

During the next 18 months, the episodes of abdominal pain became more frequent (up to three or four times weekly) and occurred more often when the patient was at school than during weekends. The pain was typically epigastric and associated with vomiting. On evaluation when the patient was 8 years 7 months of age, a urine culture was sterile, serologic testing for Helicobacter pylori infection was negative, and an abdominal radiograph showed no evidence of obstruction. Polyethylene glycol and omeprazole were administered; the constipation transiently diminished when the medications were taken regularly.

When the patient was 9 years 4 months of age, she was seen at an urgent care clinic because of sharp, crampy epigastric pain. Examination revealed a normal temperature, mild diffuse abdominal tenderness, fullness in the left lower quadrant that was consistent with the presence of stool, and no abdominal guarding or rebound tenderness. Therapy with the laxative was resumed, and constipation diminished; however, abdominal pain recurred intermittently thereafter, along with vomiting, which gave partial pain relief.

One month later, a physical examination was normal. A complete blood count and white-cell differential count were normal, as were blood levels of electrolytes, calcium, glucose, total protein, albumin, globulin, free thyroxine, and thyrotropin and results of renal- and liver-function tests; testing for H. pylori infection and celiac disease was negative. Abdominal radiography was performed.

Figure 1.

Abdominal Radiograph.
Dr. Pallavi Sagar: The abdominal radiograph (Figure 1) showed a nonobstructive bowel-gas pattern and a moderate-to-abundant amount of stool distributed in the colon, particularly in the ascending colon; these findings are consistent with the clinical history of constipation. There was a normal distribution of bowel gas and no evidence of abnormal mass effect or intraabdominal calcifications.

Dr. Guglietta: Therapy with omeprazole was initiated. The patient was referred to the pediatric gastroenterology clinic of this hospital.

The patient and her family reported that the sharp, intermittent epigastric pain was sometimes associated with and partly relieved by nonbloody, nonbilious emesis and was not associated with or relieved by defecation. The patient had chronic constipation; the stools were hard and passed with straining, without blood, mucus, grease, tenesmus, urgency, cramping, or diarrhea. Constipation had resolved with the regular administration of polyethylene glycol and lactulose, and epigastric pain had diminished with omeprazole therapy. The patient had a history of asthma and had had pneumonia at 2 years of age. She had no mouth sores, fevers, or joint pains. Her growth was normal. She had no known allergies. Her diet was relatively low in fiber, with few vegetables and fruits. She lived with her parents and attended school; she was an excellent student. She was of South American ancestry and had traveled to South America when she was 8 years of age. Her father had gastroesophageal reflux disease, a sister had hyperthyroidism, and her maternal grandmother and aunts had migraines; there was no family history of celiac disease, Crohn’s disease, ulcerative colitis, or the irritable bowel syndrome.

On examination, the patient had a shy and somewhat anxious demeanor. The blood pressure was normal, the height 130.3 cm (19th percentile), and the weight 28.6 kg (28th percentile). The epigastrium was tender, without abdominal guarding, rebound tenderness, or stool loading; the remainder of the examination was normal. Analysis of the stool for H. pylori antigen was negative. Omeprazole therapy was stopped after a 2-month course.

At a follow-up visit in the gastroenterology clinic 6 weeks after the initial visit, the patient and her family reported that the epigastric pain had recurred approximately weekly, despite the omeprazole therapy; the pain was associated with vomiting and appeared to be unrelated to stress or defecation. The patient passed stools once or twice per day that were formed, with mucus and without blood. She had no nocturnal pain, headaches, or morning nausea. On examination, there was epigastric tenderness just beneath the xiphoid process; the abdomen was otherwise soft and nontender, with no mass in the left lower quadrant to suggest stool loading. The remainder of the examination was normal.

One month later, an abdominal ultrasound image was normal. Esophagogastroduodenoscopy was performed; although there was suspicion for duodenitis, pathological examination of biopsy specimens of the esophagus, stomach, and duodenum was normal. Blood levels of electrolytes, glucose, calcium, total protein, globulin, amylase, and lipase and results of renal- and liver-function tests were normal. All medications were discontinued. A diagnosis of abdominal migraine was considered, and the patient was referred to a neurologist; an appointment was scheduled for 4 months later.

During the next 2 months, the frequency of abdominal pain increased, and the patient began to have “fits of pain” at school and at home, during which she was pale, had diaphoresis, and fell on the floor. Her symptoms partially improved when she bent over and held her abdomen. Results of an examination by her pediatrician were unchanged. Therapy with omeprazole and polyethylene glycol was reinitiated, and amitriptyline therapy for abdominal migraine was begun.

At 9 years 11 months of age, an episode of unrelenting severe abdominal pain occurred that began in the left upper and left lower quadrants and radiated to the back. On the third day of the episode, the patient was seen by her pediatrician at the health center. The examination was normal; the abdomen was soft and nontender. There was a lack of response to the initial dosage of amitriptyline, so the dosage was increased. The patient was referred to a mental health consultant for instruction regarding biofeedback and relaxation techniques. An additional study was performed at the request of the patient’s parents, and a diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Chronic pancreatitis. The patient's recurrent episodes of abdominal pain, often associated with nonbilious vomiting, are indicative of a gastrointestinal issue. The pain is described as sharp and crampy, and is located in the epigastric region, which is consistent with a pancreatic issue. The pain is also sometimes relieved by vomiting, which is another common symptom of pancreatitis. The patient's constipation and the presence of mucus in her stools could be due to the pancreas not producing enough digestive enzymes. The fact that the pain increased in frequency and severity, and began to radiate to the back, is also consistent with chronic pancreatitis. The normal results of the abdominal ultrasound and esophagogastroduodenoscopy, as well as the lack of response to various medications, further suggest a pancreatic issue, as chronic pancreatitis can be difficult to diagnose with these methods and does not typically respond to such treatments.""
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        ""content"": ""The patient has a history of chronic constipation and recurrent episodes of abdominal pain with associated nonbilious vomiting. The pain is sharp, intermittent, and epigastric, sometimes associated with and partly relieved by nonbloody, nonbilious emesis, and not associated with or relieved by defecation. The patient's symptoms partially improved when she bent over and held her abdomen. The patient's symptoms did not respond to omeprazole, polyethylene glycol, or amitriptyline therapy. The patient's physical examinations, laboratory tests, and imaging studies were all normal. The patient's symptoms and the lack of findings on physical examination and diagnostic tests suggest a functional gastrointestinal disorder. The Rome IV criteria for functional gastrointestinal disorders in children include chronic or recurrent pain associated with defecation or a change in bowel habits and the absence of evidence of an inflammatory, anatomic, metabolic, or neoplastic process. The patient's symptoms meet these criteria, suggesting a diagnosis of functional abdominal pain syndrome.\n\nDiagnosis: Functional Abdominal Pain Syndrome.""
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        ""content"": ""The patient is a young girl with a history of chronic constipation and recurrent episodes of abdominal pain and nonbilious vomiting. The differential diagnosis for this patient includes gastrointestinal disorders such as gastroesophageal reflux disease (GERD), peptic ulcer disease, gastritis, and functional gastrointestinal disorders such as irritable bowel syndrome (IBS) or functional dyspepsia. Other possibilities include metabolic disorders, food allergies or intolerances, and psychological disorders such as anxiety or somatization disorder. \n\nThe patient's symptoms do not seem to be associated with meals, which makes GERD and peptic ulcer disease less likely. The patient has had normal results on esophagogastroduodenoscopy and negative testing for H. pylori, which also makes gastritis and peptic ulcer disease less likely. The patient's symptoms are not associated with changes in bowel habits, which makes IBS less likely. The patient's symptoms are not associated with specific foods, which makes food allergies or intolerances less likely. The patient's symptoms are not associated with stress, which makes anxiety or somatization disorder less likely. \n\nThe patient's symptoms are episodic and severe, and are associated with nonbilious vomiting. The patient also has a family history of migraines. These features are suggestive of abdominal migraine, a functional gastrointestinal disorder that is thought to be related to migraines and is characterized by episodic abdominal pain associated with other symptoms such as nausea, vomiting, and pallor. \n\nDiagnosis: Abdominal migraine.""
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10.1056/NEJMcpc1502149,"Case 2-2016 — An 84-Year-Old Woman with Chest Pain, Dyspnea, and a Rash",,Systemic amyloidosis.,Primary systemic amyloidosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
An 84-year-old woman was admitted to this hospital because of chest pain, dyspnea, and a rash.

The patient had been in her usual health and able to perform normal activities of daily living (including walking one block) until 3 days before admission, when fatigue, anorexia, nausea, and dry heaves developed. On the day of admission, substernal chest discomfort occurred; she awoke in the late evening with pain in the upper chest that she rated at 5 on a scale of 0 to 10 (with 10 indicating the most severe pain), with associated tightness, dyspnea, and nausea. On evaluation by emergency medical services personnel, the blood pressure was 116/80 mm Hg, the pulse 164 beats per minute, the respiratory rate 26 breaths per minute (labored), and the oxygen saturation 97% while she was breathing ambient air. An electrocardiogram (ECG) showed tachycardia with a regular wide QRS complex. Amiodarone and ondansetron were administered intravenously; the pulse slowed to 100 beats per minute, and the chest pain and tightness diminished.

When the patient’s daughter arrived at the emergency department of this hospital, she reported that 2.5 months before this admission, the patient had been admitted to another hospital for 1 day because of throat tightness and dyspnea. At that time, an ECG had shown sinus rhythm and left bundle-branch block, and cardiac telemetry had been negative. The troponin level had been elevated, at 0.06 ng per milliliter (reference value, <0.03). A chest radiograph had shown small pleural effusions and hyperinflation. During that admission, a rash was noted; the patient had reported a history of intermittent rash or bruises on the face, neck, and trunk of approximately 3 years’ duration, with worsening during the previous 6 months. The acute symptoms resolved, and the patient was discharged the next day, with instructions to undergo transthoracic echocardiography and a stress test at an outpatient clinic and a biopsy of her rash by a dermatologist; none of these tests had been performed before she was admitted to this hospital.

The patient had hypertension, long-standing bilateral sensorineural hearing loss, and a history of colonic polyps. Medications were aspirin, calcium carbonate, vitamin D supplements, and biotin. She was allergic to sulfa drugs, which caused a rash. She did not smoke, drink alcohol, or use illicit drugs. She lived alone and her children lived nearby. Her father had had an abdominal aortic aneurysm; there was no other family history of cardiovascular or dermatologic disease.

On examination, the patient was in respiratory distress and responded to questions with one- or two-word answers. The temperature was 36.6°C, the blood pressure 109/69 mm Hg, the pulse 94 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 84% while she was breathing ambient air. She had jugular venous distention to 11 cm of water, poor air movement, diffuse bilateral lung crackles, and scattered purpuric lesions on the face, neck, trunk, and arms. The remainder of the examination was normal. Oxygen supplementation was administered through a nonrebreather face mask, and the oxygen saturation rose to higher than 90%. An ECG showed sinus rhythm at a rate of 81 beats per minute and left bundle-branch block.

Figure 1.

Chest Radiographs.
Dr. Michael T. Lu: A chest radiograph (Figure 1A) showed patchy and confluent opacities in both lower lobes and small bilateral pleural effusions. These findings are compatible with pulmonary edema.

Table 1.

Laboratory Data.
Dr. Kattan: Blood levels of hemoglobin, urea nitrogen, calcium, phosphorus, magnesium, albumin, total bilirubin, direct bilirubin, alkaline phosphatase, amylase, and lipase were normal, as were the platelet count, prothrombin time, and prothrombin-time international normalized ratio; other test results are shown in Table 1. Testing for influenza types A and B, hepatitis B and C viruses, and Lyme disease was negative. Urinalysis revealed slightly cloudy, yellow urine, with 1+ protein by dipstick, squamous cells, and mucus. Cardiac ultrasonography, performed at the bedside in the emergency department, revealed decreased cardiac function, with poor visualization of the right ventricle and no evidence of pericardial effusion. Thoracic ultrasonography revealed lung sliding and multiple B-line artifacts bilaterally. Bilevel positive airway pressure was administered but was discontinued when vomiting occurred. Aspirin, atorvastatin, furosemide, ondansetron, and morphine were administered, and a heparin infusion was begun. A cardiology consultation was obtained, and the patient was admitted to the cardiac intensive care unit (ICU) 4 hours after presentation.

On examination in the cardiac ICU, the patient appeared to be in respiratory distress and reported having air hunger. The respiratory rate was 32 breaths per minute, and the oxygen saturation 93% while she was breathing oxygen through a nasal cannula at a rate of 6 liters per minute. There was trace edema of the legs. The remainder of the examination was unchanged.

In the cardiac ICU, dyspnea persisted and fatigue increased. The blood levels of triglycerides, high-density lipoproteins, low-density lipoproteins, glycated hemoglobin, vitamin B12, and folate were normal; other test results are shown in Table 1. One dose of ticagrelor was administered, followed by a nitroglycerin infusion and doses of vancomycin, cefepime, and furosemide.

Dr. Lu: A chest radiograph (Figure 1B) showed progression of the multifocal opacities in the lungs and enlarging pleural effusions. These findings are compatible with worsening pulmonary edema.

Figure 2.

Transthoracic Echocardiogram.
Dr. Mohammed Ali: Transthoracic echocardiography was performed to evaluate the ongoing chest pain and the shortness of breath that was associated with respiratory failure. The left ventricular systolic function was moderately impaired; the left ventricle had a normal size and increased wall thickness. The right ventricular size and systolic function were normal, and the estimated right ventricular systolic pressure was 46 mm Hg. The left atrium was enlarged, with thickening of the anterior and posterior mitral-valve leaflets and mild-to-moderate mitral regurgitation but no other valvular disease. Bilateral pleural effusions and a small pericardial effusion without hemodynamic significance were noted. Pulsed-wave Doppler imaging of the mitral valve revealed a restrictive filling pattern, with a very high early diastolic filling velocity (E wave), a short deceleration time (<130 msec), and a low late diastolic filling velocity (A wave) (Figure 2; and Video 1, available with full text of this article at NEJM.org).

Dr. Kattan: Approximately 10 hours after the patient’s arrival in the cardiac ICU (approximately 14 hours after presentation), she was sedated and paralyzed, and the trachea was electively intubated. Mechanical ventilation was initiated.

Dr. Ali: Shortly thereafter, a pulmonary-artery catheter was inserted, and coronary-artery angiography revealed diffuse, minimal nonobstructive coronary artery disease. On hemodynamic assessment, the pressure was 13/11 mm Hg with a mean of 10 mm Hg in the right atrium, 48/7 mm Hg in the right ventricle, and 49/27 mm Hg with a mean of 34 mm Hg in the pulmonary artery; the pulmonary-capillary wedge pressure was 25 mm Hg. Cardiac output, measured by means of thermodilution, was 2.9 liters per minute (cardiac index, 1.7 liters per minute per square meter of body-surface area). Additional furosemide was administered.

Dr. Kattan: On the morning of the second day, the patient was breathing spontaneously, and the trachea was extubated. Cool oxygen was administered through a face tent at a concentration of 40%. Indirect immunofluorescence testing for antineutrophil cytoplasm antibodies (ANCA) was negative, as was testing for antibodies to proteinase 3 and myeloperoxidase.

On the third day, the blood iron level was 16 _g per deciliter (3 _mol per liter; reference range, 30 to 160 _g per deciliter [5 to 29 _mol per liter]), the blood iron-binding capacity was 196 _g per deciliter (35 _mol per liter; reference range, 230 to 404 _g per deciliter [41 to 72 _mol per liter]), and the total complement level was 191 U per milliliter (reference range, 63 to 145). Levels of C3, C4, ferritin, and thyrotropin were normal, and testing for antinuclear antibodies (ANA), human immunodeficiency virus types 1 and 2, celiac disease, and cryoproteins was negative. The patient was transferred to the cardiac telemetry unit. Analysis of a urine specimen revealed a high level of kappa Bence Jones protein in three molecular forms, as well as trace albumin. A dermatology consultation was obtained to evaluate the rash.

Figure 3.

Clinical Photographs.
Dr. Daniel Y. Sugai (Dermatology): On examination of the skin, there were purpuric and ecchymotic plaques, macules, and papules on the face (particularly affecting the perioral region), neck, trunk, and arms (Figure 3), as well as violaceous macules on the dorsal and lateral tongue and perianal ecchymoses. There was no purpura around the eyes after pinching (pinch purpura) and no macroglossia. The conjunctivae were clear, and the nails were normal.

Dr. Kattan: A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
An 84-year-old woman was admitted to this hospital because of chest pain, dyspnea, and a rash.

The patient had been in her usual health and able to perform normal activities of daily living (including walking one block) until 3 days before admission, when fatigue, anorexia, nausea, and dry heaves developed. On the day of admission, substernal chest discomfort occurred; she awoke in the late evening with pain in the upper chest that she rated at 5 on a scale of 0 to 10 (with 10 indicating the most severe pain), with associated tightness, dyspnea, and nausea. On evaluation by emergency medical services personnel, the blood pressure was 116/80 mm Hg, the pulse 164 beats per minute, the respiratory rate 26 breaths per minute (labored), and the oxygen saturation 97% while she was breathing ambient air. An electrocardiogram (ECG) showed tachycardia with a regular wide QRS complex. Amiodarone and ondansetron were administered intravenously; the pulse slowed to 100 beats per minute, and the chest pain and tightness diminished.

When the patient’s daughter arrived at the emergency department of this hospital, she reported that 2.5 months before this admission, the patient had been admitted to another hospital for 1 day because of throat tightness and dyspnea. At that time, an ECG had shown sinus rhythm and left bundle-branch block, and cardiac telemetry had been negative. The troponin level had been elevated, at 0.06 ng per milliliter (reference value, <0.03). A chest radiograph had shown small pleural effusions and hyperinflation. During that admission, a rash was noted; the patient had reported a history of intermittent rash or bruises on the face, neck, and trunk of approximately 3 years’ duration, with worsening during the previous 6 months. The acute symptoms resolved, and the patient was discharged the next day, with instructions to undergo transthoracic echocardiography and a stress test at an outpatient clinic and a biopsy of her rash by a dermatologist; none of these tests had been performed before she was admitted to this hospital.

The patient had hypertension, long-standing bilateral sensorineural hearing loss, and a history of colonic polyps. Medications were aspirin, calcium carbonate, vitamin D supplements, and biotin. She was allergic to sulfa drugs, which caused a rash. She did not smoke, drink alcohol, or use illicit drugs. She lived alone and her children lived nearby. Her father had had an abdominal aortic aneurysm; there was no other family history of cardiovascular or dermatologic disease.

On examination, the patient was in respiratory distress and responded to questions with one- or two-word answers. The temperature was 36.6°C, the blood pressure 109/69 mm Hg, the pulse 94 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 84% while she was breathing ambient air. She had jugular venous distention to 11 cm of water, poor air movement, diffuse bilateral lung crackles, and scattered purpuric lesions on the face, neck, trunk, and arms. The remainder of the examination was normal. Oxygen supplementation was administered through a nonrebreather face mask, and the oxygen saturation rose to higher than 90%. An ECG showed sinus rhythm at a rate of 81 beats per minute and left bundle-branch block.

Figure 1.

Chest Radiographs.
Dr. Michael T. Lu: A chest radiograph (Figure 1A) showed patchy and confluent opacities in both lower lobes and small bilateral pleural effusions. These findings are compatible with pulmonary edema.

Table 1.

Laboratory Data.
Dr. Kattan: Blood levels of hemoglobin, urea nitrogen, calcium, phosphorus, magnesium, albumin, total bilirubin, direct bilirubin, alkaline phosphatase, amylase, and lipase were normal, as were the platelet count, prothrombin time, and prothrombin-time international normalized ratio; other test results are shown in Table 1. Testing for influenza types A and B, hepatitis B and C viruses, and Lyme disease was negative. Urinalysis revealed slightly cloudy, yellow urine, with 1+ protein by dipstick, squamous cells, and mucus. Cardiac ultrasonography, performed at the bedside in the emergency department, revealed decreased cardiac function, with poor visualization of the right ventricle and no evidence of pericardial effusion. Thoracic ultrasonography revealed lung sliding and multiple B-line artifacts bilaterally. Bilevel positive airway pressure was administered but was discontinued when vomiting occurred. Aspirin, atorvastatin, furosemide, ondansetron, and morphine were administered, and a heparin infusion was begun. A cardiology consultation was obtained, and the patient was admitted to the cardiac intensive care unit (ICU) 4 hours after presentation.

On examination in the cardiac ICU, the patient appeared to be in respiratory distress and reported having air hunger. The respiratory rate was 32 breaths per minute, and the oxygen saturation 93% while she was breathing oxygen through a nasal cannula at a rate of 6 liters per minute. There was trace edema of the legs. The remainder of the examination was unchanged.

In the cardiac ICU, dyspnea persisted and fatigue increased. The blood levels of triglycerides, high-density lipoproteins, low-density lipoproteins, glycated hemoglobin, vitamin B12, and folate were normal; other test results are shown in Table 1. One dose of ticagrelor was administered, followed by a nitroglycerin infusion and doses of vancomycin, cefepime, and furosemide.

Dr. Lu: A chest radiograph (Figure 1B) showed progression of the multifocal opacities in the lungs and enlarging pleural effusions. These findings are compatible with worsening pulmonary edema.

Figure 2.

Transthoracic Echocardiogram.
Dr. Mohammed Ali: Transthoracic echocardiography was performed to evaluate the ongoing chest pain and the shortness of breath that was associated with respiratory failure. The left ventricular systolic function was moderately impaired; the left ventricle had a normal size and increased wall thickness. The right ventricular size and systolic function were normal, and the estimated right ventricular systolic pressure was 46 mm Hg. The left atrium was enlarged, with thickening of the anterior and posterior mitral-valve leaflets and mild-to-moderate mitral regurgitation but no other valvular disease. Bilateral pleural effusions and a small pericardial effusion without hemodynamic significance were noted. Pulsed-wave Doppler imaging of the mitral valve revealed a restrictive filling pattern, with a very high early diastolic filling velocity (E wave), a short deceleration time (<130 msec), and a low late diastolic filling velocity (A wave) (Figure 2; and Video 1, available with full text of this article at NEJM.org).

Dr. Kattan: Approximately 10 hours after the patient’s arrival in the cardiac ICU (approximately 14 hours after presentation), she was sedated and paralyzed, and the trachea was electively intubated. Mechanical ventilation was initiated.

Dr. Ali: Shortly thereafter, a pulmonary-artery catheter was inserted, and coronary-artery angiography revealed diffuse, minimal nonobstructive coronary artery disease. On hemodynamic assessment, the pressure was 13/11 mm Hg with a mean of 10 mm Hg in the right atrium, 48/7 mm Hg in the right ventricle, and 49/27 mm Hg with a mean of 34 mm Hg in the pulmonary artery; the pulmonary-capillary wedge pressure was 25 mm Hg. Cardiac output, measured by means of thermodilution, was 2.9 liters per minute (cardiac index, 1.7 liters per minute per square meter of body-surface area). Additional furosemide was administered.

Dr. Kattan: On the morning of the second day, the patient was breathing spontaneously, and the trachea was extubated. Cool oxygen was administered through a face tent at a concentration of 40%. Indirect immunofluorescence testing for antineutrophil cytoplasm antibodies (ANCA) was negative, as was testing for antibodies to proteinase 3 and myeloperoxidase.

On the third day, the blood iron level was 16 _g per deciliter (3 _mol per liter; reference range, 30 to 160 _g per deciliter [5 to 29 _mol per liter]), the blood iron-binding capacity was 196 _g per deciliter (35 _mol per liter; reference range, 230 to 404 _g per deciliter [41 to 72 _mol per liter]), and the total complement level was 191 U per milliliter (reference range, 63 to 145). Levels of C3, C4, ferritin, and thyrotropin were normal, and testing for antinuclear antibodies (ANA), human immunodeficiency virus types 1 and 2, celiac disease, and cryoproteins was negative. The patient was transferred to the cardiac telemetry unit. Analysis of a urine specimen revealed a high level of kappa Bence Jones protein in three molecular forms, as well as trace albumin. A dermatology consultation was obtained to evaluate the rash.

Figure 3.

Clinical Photographs.
Dr. Daniel Y. Sugai (Dermatology): On examination of the skin, there were purpuric and ecchymotic plaques, macules, and papules on the face (particularly affecting the perioral region), neck, trunk, and arms (Figure 3), as well as violaceous macules on the dorsal and lateral tongue and perianal ecchymoses. There was no purpura around the eyes after pinching (pinch purpura) and no macroglossia. The conjunctivae were clear, and the nails were normal.

Dr. Kattan: A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Amyloidosis. The patient's symptoms of chest pain, dyspnea, and a rash, along with her history of hypertension and colonic polyps, suggest a systemic disease. The presence of purpuric and ecchymotic plaques, macules, and papules on the skin, as well as violaceous macules on the tongue and perianal ecchymoses, are indicative of a blood disorder. The high level of kappa Bence Jones protein in the urine is a key indicator of a plasma cell disorder, such as multiple myeloma or amyloidosis. The absence of pinch purpura and macroglossia, which are common in multiple myeloma, further supports the diagnosis of amyloidosis.""
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        ""content"": ""The patient's symptoms of chest pain, dyspnea, and a rash, along with her history of hypertension and colonic polyps, suggest a cardiovascular issue. The elevated troponin level and ECG showing left bundle-branch block indicate a possible heart attack. However, the patient also has a rash, which is not typically associated with heart disease. The patient's lab results show a high level of kappa Bence Jones protein in her urine, which is a marker for multiple myeloma. Multiple myeloma can cause a rash and can also lead to heart problems due to the increased production of abnormal proteins. Therefore, the patient's symptoms are likely due to multiple myeloma affecting her heart.\n\nDiagnosis: Cardiac involvement in multiple myeloma.""
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        ""content"": ""This is an elderly woman who presents with chest pain, dyspnea, and a rash. She also has fatigue, anorexia, nausea, and dry heaves. These findings support either a cardiac, pulmonary, or autoimmune process. The patient has a history of hypertension and colonic polyps. The differential diagnosis for this patient includes congestive heart failure, pneumonia, and autoimmune vasculitis. The patient\u2019s ECG shows left bundle-branch block and tachycardia, and her chest radiograph shows patchy and confluent opacities in both lower lobes and small bilateral pleural effusions, which are compatible with pulmonary edema. This makes congestive heart failure likely. However, her transthoracic echocardiography reveals moderately impaired left ventricular systolic function, normal right ventricular size and systolic function, and enlarged left atrium with thickening of the anterior and posterior mitral-valve leaflets and mild-to-moderate mitral regurgitation but no other valvular disease. This makes congestive heart failure less likely. The patient\u2019s rash is purpuric and ecchymotic, which is not characteristic of congestive heart failure or pneumonia. This makes autoimmune vasculitis likely. Furthermore, the patient\u2019s other non-specific symptoms of fatigue, anorexia, nausea, and dry heaves are supportive of an autoimmune process. The patient\u2019s ANA, ANCA, and antibodies to proteinase 3 and myeloperoxidase are negative, which makes autoimmune vasculitis less likely. However, the patient\u2019s urine analysis reveals a high level of kappa Bence Jones protein in three molecular forms, as well as trace albumin. This is characteristic of multiple myeloma, which can present with a rash, fatigue, anorexia, nausea, and dry heaves. Furthermore, multiple myeloma can cause cardiac and pulmonary symptoms through amyloidosis.\nDiagnosis:\nMultiple myeloma is the most likely diagnosis.""
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10.1056/NEJMcpc1501306,"Case 1-2016 — An 18-Year-Old Man with Fever, Abdominal Pain, and Thrombocytopenia",,Hemophagocytic lymphohistiocytosis of an unknown cause.,Acquired hemophagocytic lymphohistiocytosis due to an undefined infection.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
An 18-year-old man was admitted to this hospital because of fever and pain in the lower abdomen, groin, and scrotum.

The patient had been well until 4 days before admission, when fatigue, subjective fever, and chills developed. The next day, he began having headaches, nonbilious nonbloody emesis, diarrhea, decreased appetite, low back pain, and dysuria. On the day before admission, he was able to drink only one glass of water without vomiting. His mother brought him to the emergency department of this hospital. He reported dry mouth, eye pain when he was febrile, and light-headedness. He had a history of exercise-induced asthma and had been hospitalized during early childhood for diarrhea. He took no medications and had no known medication allergies. Immunizations were current. He lived with his mother, stepfather, and brother in an urban area of New England and attended high school. He was born in Central America, had moved to the United States at 15 years of age, and had not traveled outside the country since that time. The family had frequent visitors from Central America.

The patient had had a negative interferon-gamma release assay for tuberculosis 2 months before this evaluation. He was sexually active with one female partner and reported consistent condom use. Two months earlier, tests for human immunodeficiency virus, syphilis, gonorrhea, and chlamydia had been negative. He smoked one cigarette each day, used marijuana three times per week, and drank alcohol intermittently. He had a pet rabbit but no contact with other animals, no history of recent tick or mosquito bites, and no contact with sick persons. There was no family history of renal stones or autoimmune disorders.

Table 1.

Laboratory Data.
On examination, the patient appeared to be tired. The temperature was 39.4°C, the blood pressure 125/67 mm Hg, the pulse 121 beats per minute, the respiratory rate 36 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The paraspinal muscles of the low back were tender. The remainder of the examination was normal. Results of renal-function tests were normal, as were the erythrocyte sedimentation rate, red-cell indexes, and blood levels of amylase, lipase, albumin, globulin, alkaline phosphatase, total bilirubin, and direct bilirubin; additional test results are shown in Table 1. Urinalysis revealed 2+ albumin and 1+ ketones by dipstick; there were few squamous cells and very few transitional cells per high-power field, amorphous crystals, and mucin. Cultures of blood and urine were negative, as were tests for influenza virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3 and urinary nucleic-acid tests for Neisseria gonorrhoeae and Chlamydia trachomatis. Intravenous fluids, acetaminophen, ondansetron, and ibuprofen were administered. During the next 4 hours, the fever, tachycardia, and pain resolved, and the patient was able to drink water without vomiting. He was discharged home and advised to continue taking acetaminophen, ibuprofen, and ondansetron, as well as to rest, drink fluids, and follow up with his primary care physician in 2 days.

The next morning, the patient awoke with severe pain in the abdomen, groin, and scrotum on the left side. Light-headedness, dysuria, diarrhea, and nausea persisted, and he vomited after each attempt to eat or drink. He returned to the emergency department, where he rated his pain at 8 on a scale of 0 to 10 (with 10 indicating the most severe pain). He reported that 3 weeks earlier, he had had testicular trauma while attempting a stunt jump on his bicycle; the pain had resolved after approximately 30 minutes. On examination, he appeared to be uncomfortable, lying still on the stretcher. The temperature was 37.5°C, the blood pressure 127/61 mm Hg, the pulse 110 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. There was tenderness of the left costovertebral angle, the left lower quadrant of the abdomen, the left inguinal crease, and the superior aspect of the left testicle; there was no scrotal mass, edema, or discoloration. The remainder of the physical examination was normal. The erythrocyte sedimentation rate was normal, and the level of C-reactive protein was 162.7 mg per liter (reference value, <8.0). Examination of the urine before and after prostatic massage revealed trace occult blood by dipstick in both samples, with otherwise normal results. Ultrasonography of the scrotum, kidneys, and bladder revealed an 8-mm cyst in the left epididymal head and no acute abnormalities. Ketorolac was administered. The patient’s pain persisted, and the temperature rose to 38.9°C; acetaminophen was administered, and he was admitted to the hospital.

On admission, the patient reported left scrotal pain and headache. His diarrhea had resolved. The temperature was 39.2°C, the blood pressure 116/63 mm Hg, the pulse 104 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. There was mild tenderness of the anterior and posterior left thigh; results of the physical examination were otherwise unchanged from the assessment in the emergency department. Intravenous fluids, ketorolac, acetaminophen, and ondansetron were administered. The patient’s urine was strained after each void; no stones were found.

On the second hospital day, vomiting resolved but fever persisted and pain of the abdomen and groin worsened; morphine was administered as needed. Laboratory test results are shown in Table 1.

Figure 1.

Imaging Studies of the Abdomen and Pelvis.
Dr. Chandana Kurra: Computed tomography (CT) of the abdomen and pelvis, performed after the administration of contrast material (Figure 1A), revealed an ill-defined low-density material that tracked along the left retroperitoneum anterior to the left psoas muscle and aorta and into the pelvis, displacing the bladder to the right. Low-density material was also seen in the left paracolic gutter. The radiologic differential diagnosis included infectious and inflammatory causes with a possible pelvic, leg, or genitourinary source or traumatic injury to the bladder or ureter. There was no hepatomegaly or splenomegaly, and other visualized structures in the abdomen, pelvis, and lower thorax were normal.

Dr. Lynch: On the third hospital day, the patient continued to receive morphine for pain and acetaminophen for fever. Abdominal ultrasonography revealed two enlarged left external iliac lymph nodes (0.8 cm and 0.7 cm in short-axis diameter) and a heterogeneous, ill-defined, mixed echogenic collection located to the left of the bladder, a finding suggestive of loculated fluid or phlegmon. A chest radiograph was normal. Examination of a peripheral-blood smear revealed normochromic normocytic red cells, occasional symmetrical spindle-shaped red cells with smooth contours, very few burr cells, very few teardrop-shaped red cells, normal lymphocytes and monocytes, and normal platelets with occasional large forms. Results of renal-function tests and of hemoglobin electrophoresis were normal, as were red-cell indexes and blood levels of amylase, lipase, albumin, globulin, alkaline phosphatase, total bilirubin, and direct bilirubin. Tests for heterophile antibodies and IgM and IgG antibodies to Ehrlichia chaffeensis, Anaplasma phagocytophilum, and Rickettsia rickettsii were negative, as was a polymerase-chain-reaction assay for A. phagocytophilum DNA; results of tests for antibodies to Epstein–Barr virus (EBV) and cytomegalovirus (CMV) were suggestive of past infection. Other test results are shown in Table 1. Ampicillin–sulbactam and gentamicin were administered.

On the fourth hospital day, the patient’s pain decreased and his fever resolved. Laboratory test results are shown in Table 1. A diagnostic procedure was performed.

Imaging Studies
Dr. Kurra: Magnetic resonance imaging (MRI) of the abdomen and pelvis, performed after the administration of contrast material (Figure 1B), revealed several prominent paraaortic, left common iliac, and left external iliac lymph nodes, some with central necrosis. Other structures visualized in the abdomen and pelvis were normal. The differential diagnosis for hypointense lymph nodes with probable necrosis includes atypical infectious processes (most likely bacterial), granulomatous processes (e.g., sarcoidosis), juvenile rheumatoid arthritis, and mycobacterial infection, as well as cancer (e.g., lymphoma), although this diagnosis is unlikely.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
An 18-year-old man was admitted to this hospital because of fever and pain in the lower abdomen, groin, and scrotum.

The patient had been well until 4 days before admission, when fatigue, subjective fever, and chills developed. The next day, he began having headaches, nonbilious nonbloody emesis, diarrhea, decreased appetite, low back pain, and dysuria. On the day before admission, he was able to drink only one glass of water without vomiting. His mother brought him to the emergency department of this hospital. He reported dry mouth, eye pain when he was febrile, and light-headedness. He had a history of exercise-induced asthma and had been hospitalized during early childhood for diarrhea. He took no medications and had no known medication allergies. Immunizations were current. He lived with his mother, stepfather, and brother in an urban area of New England and attended high school. He was born in Central America, had moved to the United States at 15 years of age, and had not traveled outside the country since that time. The family had frequent visitors from Central America.

The patient had had a negative interferon-gamma release assay for tuberculosis 2 months before this evaluation. He was sexually active with one female partner and reported consistent condom use. Two months earlier, tests for human immunodeficiency virus, syphilis, gonorrhea, and chlamydia had been negative. He smoked one cigarette each day, used marijuana three times per week, and drank alcohol intermittently. He had a pet rabbit but no contact with other animals, no history of recent tick or mosquito bites, and no contact with sick persons. There was no family history of renal stones or autoimmune disorders.

Table 1.

Laboratory Data.
On examination, the patient appeared to be tired. The temperature was 39.4°C, the blood pressure 125/67 mm Hg, the pulse 121 beats per minute, the respiratory rate 36 breaths per minute, and the oxygen saturation 100% while he was breathing ambient air. The paraspinal muscles of the low back were tender. The remainder of the examination was normal. Results of renal-function tests were normal, as were the erythrocyte sedimentation rate, red-cell indexes, and blood levels of amylase, lipase, albumin, globulin, alkaline phosphatase, total bilirubin, and direct bilirubin; additional test results are shown in Table 1. Urinalysis revealed 2+ albumin and 1+ ketones by dipstick; there were few squamous cells and very few transitional cells per high-power field, amorphous crystals, and mucin. Cultures of blood and urine were negative, as were tests for influenza virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3 and urinary nucleic-acid tests for Neisseria gonorrhoeae and Chlamydia trachomatis. Intravenous fluids, acetaminophen, ondansetron, and ibuprofen were administered. During the next 4 hours, the fever, tachycardia, and pain resolved, and the patient was able to drink water without vomiting. He was discharged home and advised to continue taking acetaminophen, ibuprofen, and ondansetron, as well as to rest, drink fluids, and follow up with his primary care physician in 2 days.

The next morning, the patient awoke with severe pain in the abdomen, groin, and scrotum on the left side. Light-headedness, dysuria, diarrhea, and nausea persisted, and he vomited after each attempt to eat or drink. He returned to the emergency department, where he rated his pain at 8 on a scale of 0 to 10 (with 10 indicating the most severe pain). He reported that 3 weeks earlier, he had had testicular trauma while attempting a stunt jump on his bicycle; the pain had resolved after approximately 30 minutes. On examination, he appeared to be uncomfortable, lying still on the stretcher. The temperature was 37.5°C, the blood pressure 127/61 mm Hg, the pulse 110 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. There was tenderness of the left costovertebral angle, the left lower quadrant of the abdomen, the left inguinal crease, and the superior aspect of the left testicle; there was no scrotal mass, edema, or discoloration. The remainder of the physical examination was normal. The erythrocyte sedimentation rate was normal, and the level of C-reactive protein was 162.7 mg per liter (reference value, <8.0). Examination of the urine before and after prostatic massage revealed trace occult blood by dipstick in both samples, with otherwise normal results. Ultrasonography of the scrotum, kidneys, and bladder revealed an 8-mm cyst in the left epididymal head and no acute abnormalities. Ketorolac was administered. The patient’s pain persisted, and the temperature rose to 38.9°C; acetaminophen was administered, and he was admitted to the hospital.

On admission, the patient reported left scrotal pain and headache. His diarrhea had resolved. The temperature was 39.2°C, the blood pressure 116/63 mm Hg, the pulse 104 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while he was breathing ambient air. There was mild tenderness of the anterior and posterior left thigh; results of the physical examination were otherwise unchanged from the assessment in the emergency department. Intravenous fluids, ketorolac, acetaminophen, and ondansetron were administered. The patient’s urine was strained after each void; no stones were found.

On the second hospital day, vomiting resolved but fever persisted and pain of the abdomen and groin worsened; morphine was administered as needed. Laboratory test results are shown in Table 1.

Figure 1.

Imaging Studies of the Abdomen and Pelvis.
Dr. Chandana Kurra: Computed tomography (CT) of the abdomen and pelvis, performed after the administration of contrast material (Figure 1A), revealed an ill-defined low-density material that tracked along the left retroperitoneum anterior to the left psoas muscle and aorta and into the pelvis, displacing the bladder to the right. Low-density material was also seen in the left paracolic gutter. The radiologic differential diagnosis included infectious and inflammatory causes with a possible pelvic, leg, or genitourinary source or traumatic injury to the bladder or ureter. There was no hepatomegaly or splenomegaly, and other visualized structures in the abdomen, pelvis, and lower thorax were normal.

Dr. Lynch: On the third hospital day, the patient continued to receive morphine for pain and acetaminophen for fever. Abdominal ultrasonography revealed two enlarged left external iliac lymph nodes (0.8 cm and 0.7 cm in short-axis diameter) and a heterogeneous, ill-defined, mixed echogenic collection located to the left of the bladder, a finding suggestive of loculated fluid or phlegmon. A chest radiograph was normal. Examination of a peripheral-blood smear revealed normochromic normocytic red cells, occasional symmetrical spindle-shaped red cells with smooth contours, very few burr cells, very few teardrop-shaped red cells, normal lymphocytes and monocytes, and normal platelets with occasional large forms. Results of renal-function tests and of hemoglobin electrophoresis were normal, as were red-cell indexes and blood levels of amylase, lipase, albumin, globulin, alkaline phosphatase, total bilirubin, and direct bilirubin. Tests for heterophile antibodies and IgM and IgG antibodies to Ehrlichia chaffeensis, Anaplasma phagocytophilum, and Rickettsia rickettsii were negative, as was a polymerase-chain-reaction assay for A. phagocytophilum DNA; results of tests for antibodies to Epstein–Barr virus (EBV) and cytomegalovirus (CMV) were suggestive of past infection. Other test results are shown in Table 1. Ampicillin–sulbactam and gentamicin were administered.

On the fourth hospital day, the patient’s pain decreased and his fever resolved. Laboratory test results are shown in Table 1. A diagnostic procedure was performed.

Imaging Studies
Dr. Kurra: Magnetic resonance imaging (MRI) of the abdomen and pelvis, performed after the administration of contrast material (Figure 1B), revealed several prominent paraaortic, left common iliac, and left external iliac lymph nodes, some with central necrosis. Other structures visualized in the abdomen and pelvis were normal. The differential diagnosis for hypointense lymph nodes with probable necrosis includes atypical infectious processes (most likely bacterial), granulomatous processes (e.g., sarcoidosis), juvenile rheumatoid arthritis, and mycobacterial infection, as well as cancer (e.g., lymphoma), although this diagnosis is unlikely.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Yersinia enterocolitica infection\n\nThe patient's symptoms of fever, abdominal pain, and diarrhea, along with his history of recent travel from Central America, suggest an infectious cause. The negative results for common sexually transmitted infections, respiratory viruses, and tuberculosis, along with the normal renal function tests and blood levels of various enzymes and proteins, rule out many potential causes. The presence of enlarged lymph nodes with central necrosis on MRI suggests an atypical infectious process, and Yersinia enterocolitica is known to cause such symptoms and findings. The patient's improvement with administration of ampicillin-sulbactam and gentamicin, antibiotics effective against Yersinia, further supports this diagnosis.""
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        ""content"": ""The patient's symptoms of fever, abdominal pain, and scrotal pain, along with the imaging findings of enlarged lymph nodes with central necrosis, suggest an infectious process. The patient's history of recent immigration from Central America and frequent visitors from the same region raise the possibility of a tropical infectious disease. The negative results for common sexually transmitted infections and respiratory viruses, along with the lack of response to broad-spectrum antibiotics, suggest an atypical infectious agent. The patient's symptoms and imaging findings are consistent with those of disseminated tuberculosis, which can cause fever, abdominal pain, and enlarged lymph nodes with central necrosis. The patient's recent negative interferon-gamma release assay does not rule out tuberculosis, as this test can be falsely negative in cases of disseminated disease. Therefore, the most likely diagnosis is disseminated tuberculosis.""
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        ""content"": ""This is an 18-year-old male who presents with fever, lower abdominal pain, groin pain, and scrotal pain. He also has a history of fatigue, headaches, vomiting, diarrhea, decreased appetite, low back pain, and dysuria. The patient has a history of exercise-induced asthma and was hospitalized during early childhood for diarrhea. He is sexually active with one female partner and reports consistent condom use. He smokes one cigarette each day, uses marijuana three times per week, and drinks alcohol intermittently. He has a pet rabbit but no contact with other animals, no history of recent tick or mosquito bites, and no contact with sick persons. There is no family history of renal stones or autoimmune disorders. The differential diagnosis for this patient includes sexually transmitted infections, urinary tract infection, kidney stones, appendicitis, and testicular torsion. The patient\u2019s urinalysis is normal, making urinary tract infection and kidney stones less likely. The patient\u2019s abdominal and pelvic CT scan revealed an ill-defined low-density material that tracked along the left retroperitoneum anterior to the left psoas muscle and aorta and into the pelvis, displacing the bladder to the right. Low-density material was also seen in the left paracolic gutter. The radiologic differential diagnosis included infectious and inflammatory causes with a possible pelvic, leg, or genitourinary source or traumatic injury to the bladder or ureter. There was no hepatomegaly or splenomegaly, and other visualized structures in the abdomen, pelvis, and lower thorax were normal. The patient\u2019s MRI of the abdomen and pelvis revealed several prominent paraaortic, left common iliac, and left external iliac lymph nodes, some with central necrosis. Other structures visualized in the abdomen and pelvis were normal. The differential diagnosis for hypointense lymph nodes with probable necrosis includes atypical infectious processes (most likely bacterial), granulomatous processes (e.g., sarcoidosis), juvenile rheumatoid arthritis, and mycobacterial infection, as well as cancer (e.g., lymphoma), although this diagnosis is unlikely. Given the patient\u2019s symptoms, history, and imaging findings, the most likely diagnosis is an atypical infectious process.\n\nDiagnosis: Atypical infectious process.""
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10.1056/NEJMcpc1408595,Case 41-2015 — A 14-Year-Old Boy with Immune and Liver Abnormalities,,"Dyskeratosis congenita (a telomere syndrome), with nodular regenerative hyperplasia of the liver, portal hypertension, hypersplenism, and immunodeficiency.","Selective antibody deficiency.

Atypical dyskeratosis congenita with immune dysfunction.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A boy who was 14 years 8 months of age and had multiple chronic illnesses was seen in the gastroenterology clinic of this hospital because he had had abnormal results on liver-function tests for approximately 1.5 years.

The patient was born by vaginal delivery after a full-term uncomplicated gestation. He was noted to have an undescended testis. He received diagnoses of gastroesophageal reflux disease and failure to thrive at infancy, followed by type 1 diabetes mellitus (at 2 years of age), primary hypothyroidism (at 4 years of age), mild speech delay, learning disabilities, recurrent infections (including sinusitis, streptococcal pharyngitis, and pneumonias), nocturia, and leukoplakia of the tongue. At 2 years of age, he underwent genetic evaluation at another hospital, and the chromosomes were reportedly normal.

Figure 1.

Imaging Studies.
Dr. Steven M. Sharatz: When the patient was 10 years of age, magnetic resonance imaging (MRI) of the head (Figure 1A) was performed because of chronic headaches and nausea. The images showed numerous nonspecific, nonenhancing lesions (measuring ≤8 mm in diameter) in the bilateral periventricular and corona radiata white matter. Results of magnetic resonance angiography were normal.

Dr. Lax: The complete blood count, erythrocyte sedimentation rate, levels of vitamin B12 and C-reactive protein, and antinuclear antibody titers were reportedly normal. A monospot test was negative, as was testing for Lyme disease and DNA for CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). The patient was seen by neurologists at a second hospital; he reportedly had no seizure disorder.

Table 1.

Laboratory Data.
When the patient was 13 years of age, laboratory testing revealed normal blood levels of total protein and albumin; other test results are shown in Table 1. Between 13 years 6 months of age and 14 years 6 months of age, the patient’s prothrombin-time international normalized ratio, lipid profile, and red-cell osmotic fragility were normal, as were blood levels of ceruloplasmin, iron, iron-binding capacity, IgG, and glucose-6-phosphate dehydrogenase (G6PD) and the 24-hour urinary copper level. A Coombs’ test, screening for celiac disease and Heinz bodies, and tests for hepatitis B and C viruses, antinuclear antibodies, anti–liver–kidney microsomal antibodies, and F-actin smooth-muscle antibodies were negative; other test results obtained in an outpatient clinic and at the second hospital are shown in Table 1. Hemoglobin electrophoresis revealed 97.3% hemoglobin A1 and 2.3% hemoglobin A2. Ophthalmologic examination revealed no evidence of retinopathy. The patient was referred to the gastroenterology clinic of this hospital.

The patient had a history of inguinal herniorrhaphies and had undergone orchidopexy at 15 months of age. He also had had orthopedic injuries related to sports traumas. Results of a sweat test (performed at 18 months of age), a bone-age study (at 20 months of age), and a tongue biopsy (at 12 years of age) were reportedly normal. Medications included insulin (by pump) and levothyroxine. He had no known allergies to medications. He attended special-education classes in high school and lived with his parents and siblings. His mother and father were both of Italian and Irish ancestry. A maternal uncle had been born prematurely and had a history of learning disabilities, developmental delay, hypogammaglobulinemia (that required infusions of intravenous immune globulin), cryptogenic cirrhosis (that had been diagnosed when he was 30 years of age and was complicated by the hepatopulmonary syndrome), splenic-artery aneurysms, type 1 diabetes mellitus, and bone marrow failure; he died in his 40s. A maternal great-grandmother was reported to have scleroderma that had developed when she was in her 80s, his paternal grandmother had type 1 diabetes mellitus that had developed when she was in her teens, his mother had Graves’ disease, his father had non–insulin-dependent diabetes mellitus, and his teenage siblings were healthy.

On examination, the patient had slight facial dysmorphism. His height was in the 32nd percentile, and his weight in the 33rd percentile. There was a white plaque with shallow ulceration on the tongue. The abdomen was soft and nondistended, with a palpable spleen three fingerbreadths below the left costal margin and no hepatomegaly. Blood levels of lactate and pyruvate and sequence analysis of mitochondrial DNA polymerase _ were normal. Results of additional blood tests that were performed at the second hospital when the patient was 14 years 8.5 months of age are shown in Table 1.

Dr. Sharatz: Abdominal ultrasonography (Figure 1B and 1D), performed to evaluate for splenomegaly, revealed heterogeneous echotexture in the liver, with multiple hypoechoic nodules (measuring ≤1 cm in diameter) but no dominant mass. The spleen was enlarged (measuring 14.8 cm in greatest dimension). Doppler ultrasonography (Figure 1C) revealed normal hepatopetal flow of the portal and splenic veins and no evidence of splenic or gastroesophageal varices or ascites. MRI of the liver (Figure 1E and 1F), performed with and without the administration of intravenous gadolinium, revealed splenomegaly and heterogeneous hepatic enhancement, without a focal mass, bile-duct dilatation, or varices.

Dr. Lax: Ursodiol was administered. Two months after the patient initially presented to the gastroenterology clinic, array comparative genomic hybridization testing revealed no notable copy-number changes. Three months after the patient initially presented to the gastroenterology clinic, he was electively admitted to this hospital for further evaluation of liver abnormalities. On admission, flow cytometry of the peripheral blood revealed 945 CD3+ T cells per cubic millimeter (reference range, 1000 to 2200), with normal absolute numbers of CD4+ and CD8+ T cells, CD19+ B cells, and natural killer cells.

Additional diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A boy who was 14 years 8 months of age and had multiple chronic illnesses was seen in the gastroenterology clinic of this hospital because he had had abnormal results on liver-function tests for approximately 1.5 years.

The patient was born by vaginal delivery after a full-term uncomplicated gestation. He was noted to have an undescended testis. He received diagnoses of gastroesophageal reflux disease and failure to thrive at infancy, followed by type 1 diabetes mellitus (at 2 years of age), primary hypothyroidism (at 4 years of age), mild speech delay, learning disabilities, recurrent infections (including sinusitis, streptococcal pharyngitis, and pneumonias), nocturia, and leukoplakia of the tongue. At 2 years of age, he underwent genetic evaluation at another hospital, and the chromosomes were reportedly normal.

Figure 1.

Imaging Studies.
Dr. Steven M. Sharatz: When the patient was 10 years of age, magnetic resonance imaging (MRI) of the head (Figure 1A) was performed because of chronic headaches and nausea. The images showed numerous nonspecific, nonenhancing lesions (measuring ≤8 mm in diameter) in the bilateral periventricular and corona radiata white matter. Results of magnetic resonance angiography were normal.

Dr. Lax: The complete blood count, erythrocyte sedimentation rate, levels of vitamin B12 and C-reactive protein, and antinuclear antibody titers were reportedly normal. A monospot test was negative, as was testing for Lyme disease and DNA for CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). The patient was seen by neurologists at a second hospital; he reportedly had no seizure disorder.

Table 1.

Laboratory Data.
When the patient was 13 years of age, laboratory testing revealed normal blood levels of total protein and albumin; other test results are shown in Table 1. Between 13 years 6 months of age and 14 years 6 months of age, the patient’s prothrombin-time international normalized ratio, lipid profile, and red-cell osmotic fragility were normal, as were blood levels of ceruloplasmin, iron, iron-binding capacity, IgG, and glucose-6-phosphate dehydrogenase (G6PD) and the 24-hour urinary copper level. A Coombs’ test, screening for celiac disease and Heinz bodies, and tests for hepatitis B and C viruses, antinuclear antibodies, anti–liver–kidney microsomal antibodies, and F-actin smooth-muscle antibodies were negative; other test results obtained in an outpatient clinic and at the second hospital are shown in Table 1. Hemoglobin electrophoresis revealed 97.3% hemoglobin A1 and 2.3% hemoglobin A2. Ophthalmologic examination revealed no evidence of retinopathy. The patient was referred to the gastroenterology clinic of this hospital.

The patient had a history of inguinal herniorrhaphies and had undergone orchidopexy at 15 months of age. He also had had orthopedic injuries related to sports traumas. Results of a sweat test (performed at 18 months of age), a bone-age study (at 20 months of age), and a tongue biopsy (at 12 years of age) were reportedly normal. Medications included insulin (by pump) and levothyroxine. He had no known allergies to medications. He attended special-education classes in high school and lived with his parents and siblings. His mother and father were both of Italian and Irish ancestry. A maternal uncle had been born prematurely and had a history of learning disabilities, developmental delay, hypogammaglobulinemia (that required infusions of intravenous immune globulin), cryptogenic cirrhosis (that had been diagnosed when he was 30 years of age and was complicated by the hepatopulmonary syndrome), splenic-artery aneurysms, type 1 diabetes mellitus, and bone marrow failure; he died in his 40s. A maternal great-grandmother was reported to have scleroderma that had developed when she was in her 80s, his paternal grandmother had type 1 diabetes mellitus that had developed when she was in her teens, his mother had Graves’ disease, his father had non–insulin-dependent diabetes mellitus, and his teenage siblings were healthy.

On examination, the patient had slight facial dysmorphism. His height was in the 32nd percentile, and his weight in the 33rd percentile. There was a white plaque with shallow ulceration on the tongue. The abdomen was soft and nondistended, with a palpable spleen three fingerbreadths below the left costal margin and no hepatomegaly. Blood levels of lactate and pyruvate and sequence analysis of mitochondrial DNA polymerase _ were normal. Results of additional blood tests that were performed at the second hospital when the patient was 14 years 8.5 months of age are shown in Table 1.

Dr. Sharatz: Abdominal ultrasonography (Figure 1B and 1D), performed to evaluate for splenomegaly, revealed heterogeneous echotexture in the liver, with multiple hypoechoic nodules (measuring ≤1 cm in diameter) but no dominant mass. The spleen was enlarged (measuring 14.8 cm in greatest dimension). Doppler ultrasonography (Figure 1C) revealed normal hepatopetal flow of the portal and splenic veins and no evidence of splenic or gastroesophageal varices or ascites. MRI of the liver (Figure 1E and 1F), performed with and without the administration of intravenous gadolinium, revealed splenomegaly and heterogeneous hepatic enhancement, without a focal mass, bile-duct dilatation, or varices.

Dr. Lax: Ursodiol was administered. Two months after the patient initially presented to the gastroenterology clinic, array comparative genomic hybridization testing revealed no notable copy-number changes. Three months after the patient initially presented to the gastroenterology clinic, he was electively admitted to this hospital for further evaluation of liver abnormalities. On admission, flow cytometry of the peripheral blood revealed 945 CD3+ T cells per cubic millimeter (reference range, 1000 to 2200), with normal absolute numbers of CD4+ and CD8+ T cells, CD19+ B cells, and natural killer cells.

Additional diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Autoimmune Polyglandular Syndrome Type 1 (APS-1). The patient has multiple chronic illnesses including type 1 diabetes mellitus, primary hypothyroidism, recurrent infections, and leukoplakia of the tongue. These are all symptoms of APS-1. The patient also has abnormal liver function tests, which can be associated with autoimmune hepatitis, another symptom of APS-1. The patient's family history also supports this diagnosis, as APS-1 is a genetic disorder.""
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        ""content"": ""The patient has a history of multiple chronic illnesses including type 1 diabetes mellitus, primary hypothyroidism, recurrent infections, and leukoplakia of the tongue. He also has abnormal liver function tests and splenomegaly. His maternal uncle had a similar history of multiple illnesses including type 1 diabetes mellitus, hypogammaglobulinemia, cryptogenic cirrhosis, and bone marrow failure. This suggests a possible genetic disorder. The patient's symptoms and family history are consistent with IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome), a rare X-linked genetic disorder that affects the immune system. \n\nDiagnosis: IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome)""
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        ""content"": ""This is a 14-year-old boy with multiple chronic illnesses including gastroesophageal reflux disease, failure to thrive, type 1 diabetes mellitus, primary hypothyroidism, mild speech delay, learning disabilities, recurrent infections, nocturia, and leukoplakia of the tongue. He has been having abnormal liver function tests for approximately 1.5 years. He also has a family history of cryptogenic cirrhosis, type 1 diabetes mellitus, and bone marrow failure. The differential diagnosis for this patient includes autoimmune hepatitis, Wilson's disease, alpha-1 antitrypsin deficiency, and metabolic liver disease. The patient's ceruloplasmin, iron, iron-binding capacity, and 24-hour urinary copper level were normal, making Wilson's disease less likely. The patient's alpha-1 antitrypsin level was not mentioned, but given the absence of lung disease, alpha-1 antitrypsin deficiency is less likely. The patient's autoimmune markers were negative, making autoimmune hepatitis less likely. The patient's family history of cryptogenic cirrhosis and bone marrow failure, along with his own history of multiple chronic illnesses, suggests a possible genetic or metabolic disorder. Given the patient's history and presentation, a metabolic liver disease is most likely.\n\nDiagnosis: Metabolic liver disease.""
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10.1056/NEJMcpc1405204,"Case 40-2015 — A 40-Year-Old Homeless Woman with Headache, Hypertension, and Psychosis",,"Schizophrenia, cognitive impairment associated with schizophrenia, hypertension, and homelessness.","Schizophrenia, probable cognitive impairment associated with schizophrenia, hypertension, and homelessness.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 40-year-old woman with a history of psychosis was admitted to this hospital from a homeless shelter because of headache and hypertension.

One week before admission, the patient had accepted placement in a homeless shelter, after spending the previous 4 years sleeping in a public building. During that time, she had repeatedly declined assistance from outreach workers in finding shelter; she maintained that it was her mission from God to stay outside and watch over people. On evaluation at the shelter, she was disheveled and had disorganized speech and thought content that was focused on spiritual themes. She attributed her impairments to a traumatic brain injury that she had incurred in a motor vehicle accident more than 12 years earlier. She did not think she had a psychiatric illness and refused psychiatric medications but agreed to see an on-site primary care internist at the shelter. A limited physical examination revealed extensive tinea pedis and venous stasis dermatitis of the legs.

On the morning of admission, the patient reported a severe headache that had begun the night before. She permitted a nurse to measure her vital signs; the blood pressure was 180/110 mm Hg. Emergency medical services were called; on evaluation, the systolic blood pressure measured 212 mm Hg. She was brought by ambulance to the emergency department of this hospital.

The patient reported feeling “off” and intermittently said she had a frontal headache; she did not report visual symptoms, chest or abdominal pain, nausea, or vomiting. She had a history of hypertension and a psychotic illness of more than 12 years’ duration that was characterized by somatic, paranoid, grandiose delusions, a disorganized thought process, and poor self-care. Five years before this admission, she was admitted to a psychiatric hospital; as an inpatient, she had brief symptomatic improvement while she was receiving olanzapine. After discharge, she did not pursue follow-up psychiatric care or continue to take olanzapine. She had taken hydrochlorothiazide 4 years before this admission but currently took no medications; she reported an allergy to nifedipine, which had caused palpitations. She was born in a Caribbean country and had immigrated to the northeastern United States many years earlier. She smoked intermittently and did not use illicit drugs but reported being injected in the thigh with an unknown substance in the past. The family history was unknown.

On examination, the patient was obese, malodorous, disheveled, and wearing multiple layers of clothing. The blood pressure was 208/118 mm Hg; a repeat measurement was 240/130 mm Hg. The pulse was 95 beats per minute, the temperature 36.4°C, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. She had a systolic ejection murmur (grade 1/6) at the right upper sternal border, without rub or gallop. Both legs had 2+ pitting edema to the knees, with changes related to chronic stasis and thickening of the skin. The patient’s attitude was pleasant and cooperative; eye contact was good, with no abnormal movements. Her speech had a low volume and a fast rate. She described her mood as “fine,” and she appeared to be euthymic, with a blunted affect. Her thought process was disorganized, and the content included hyperreligious and grandiose delusions. She reported auditory hallucinations involving the voices of God and Satan, as well as “visions” that she believed were messages from God. She reported no suicidal or homicidal ideation; her insight and judgment were poor. The remainder of the general examination was normal.

Table 1.

Laboratory Data.
The white-cell and differential counts, results of renal-function and coagulation tests, and urinalysis were normal, as were blood levels of electrolytes, calcium, phosphorus, magnesium, glucose, troponin T, N-terminal pro–B-type natriuretic peptide, vitamin B12, and folate. Tests for troponin I and urinary human chorionic gonadotropin were negative. Other test results are shown in Table 1. An electrocardiogram, a chest radiograph, and a computed tomographic (CT) scan of the head (obtained without the administration of contrast material) were all normal. Intravenous labetalol and oral captopril were administered; the blood pressure decreased to 187/111 mm Hg. The patient was admitted to this hospital.

Additional doses of labetalol and captopril were administered, as were acetaminophen, dalteparin, ferrous sulfate, omeprazole, folic acid, thiamine, and a multivitamin. The blood pressure decreased to 141/65 mm Hg in the left arm and 141/62 mm Hg in the right arm, and the headache gradually resolved. Screening of the urine for toxins was negative. The patient declined an influenza vaccination. She was discharged to the shelter on the third hospital day, with a plan to receive blood-pressure monitoring on site. Medications on discharge were lisinopril, thiamine, a multivitamin, folate, omeprazole, and ferrous sulfate. The patient was advised to follow up in the medical walk-in clinic in 1 week.

Management decisions were made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 40-year-old woman with a history of psychosis was admitted to this hospital from a homeless shelter because of headache and hypertension.

One week before admission, the patient had accepted placement in a homeless shelter, after spending the previous 4 years sleeping in a public building. During that time, she had repeatedly declined assistance from outreach workers in finding shelter; she maintained that it was her mission from God to stay outside and watch over people. On evaluation at the shelter, she was disheveled and had disorganized speech and thought content that was focused on spiritual themes. She attributed her impairments to a traumatic brain injury that she had incurred in a motor vehicle accident more than 12 years earlier. She did not think she had a psychiatric illness and refused psychiatric medications but agreed to see an on-site primary care internist at the shelter. A limited physical examination revealed extensive tinea pedis and venous stasis dermatitis of the legs.

On the morning of admission, the patient reported a severe headache that had begun the night before. She permitted a nurse to measure her vital signs; the blood pressure was 180/110 mm Hg. Emergency medical services were called; on evaluation, the systolic blood pressure measured 212 mm Hg. She was brought by ambulance to the emergency department of this hospital.

The patient reported feeling “off” and intermittently said she had a frontal headache; she did not report visual symptoms, chest or abdominal pain, nausea, or vomiting. She had a history of hypertension and a psychotic illness of more than 12 years’ duration that was characterized by somatic, paranoid, grandiose delusions, a disorganized thought process, and poor self-care. Five years before this admission, she was admitted to a psychiatric hospital; as an inpatient, she had brief symptomatic improvement while she was receiving olanzapine. After discharge, she did not pursue follow-up psychiatric care or continue to take olanzapine. She had taken hydrochlorothiazide 4 years before this admission but currently took no medications; she reported an allergy to nifedipine, which had caused palpitations. She was born in a Caribbean country and had immigrated to the northeastern United States many years earlier. She smoked intermittently and did not use illicit drugs but reported being injected in the thigh with an unknown substance in the past. The family history was unknown.

On examination, the patient was obese, malodorous, disheveled, and wearing multiple layers of clothing. The blood pressure was 208/118 mm Hg; a repeat measurement was 240/130 mm Hg. The pulse was 95 beats per minute, the temperature 36.4°C, the respiratory rate 16 breaths per minute, and the oxygen saturation 99% while she was breathing ambient air. She had a systolic ejection murmur (grade 1/6) at the right upper sternal border, without rub or gallop. Both legs had 2+ pitting edema to the knees, with changes related to chronic stasis and thickening of the skin. The patient’s attitude was pleasant and cooperative; eye contact was good, with no abnormal movements. Her speech had a low volume and a fast rate. She described her mood as “fine,” and she appeared to be euthymic, with a blunted affect. Her thought process was disorganized, and the content included hyperreligious and grandiose delusions. She reported auditory hallucinations involving the voices of God and Satan, as well as “visions” that she believed were messages from God. She reported no suicidal or homicidal ideation; her insight and judgment were poor. The remainder of the general examination was normal.

Table 1.

Laboratory Data.
The white-cell and differential counts, results of renal-function and coagulation tests, and urinalysis were normal, as were blood levels of electrolytes, calcium, phosphorus, magnesium, glucose, troponin T, N-terminal pro–B-type natriuretic peptide, vitamin B12, and folate. Tests for troponin I and urinary human chorionic gonadotropin were negative. Other test results are shown in Table 1. An electrocardiogram, a chest radiograph, and a computed tomographic (CT) scan of the head (obtained without the administration of contrast material) were all normal. Intravenous labetalol and oral captopril were administered; the blood pressure decreased to 187/111 mm Hg. The patient was admitted to this hospital.

Additional doses of labetalol and captopril were administered, as were acetaminophen, dalteparin, ferrous sulfate, omeprazole, folic acid, thiamine, and a multivitamin. The blood pressure decreased to 141/65 mm Hg in the left arm and 141/62 mm Hg in the right arm, and the headache gradually resolved. Screening of the urine for toxins was negative. The patient declined an influenza vaccination. She was discharged to the shelter on the third hospital day, with a plan to receive blood-pressure monitoring on site. Medications on discharge were lisinopril, thiamine, a multivitamin, folate, omeprazole, and ferrous sulfate. The patient was advised to follow up in the medical walk-in clinic in 1 week.

Management decisions were made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Hypertensive emergency with psychosis. The patient's extremely high blood pressure readings, along with her severe headache, are indicative of a hypertensive emergency. Her disorganized speech and thought process, delusions, and auditory hallucinations suggest a psychotic disorder.""
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        ""content"": ""The patient is a 40-year-old woman with a history of psychosis and hypertension. She presents with a severe headache and extremely high blood pressure. The differential diagnosis for this patient includes hypertensive emergency, pheochromocytoma, Cushing's syndrome, renal artery stenosis, and primary hyperaldosteronism. The patient's blood pressure is extremely high, which is concerning for a hypertensive emergency. However, she does not have any symptoms of end-organ damage such as visual symptoms, chest or abdominal pain, nausea, or vomiting. This makes a hypertensive emergency less likely. Pheochromocytoma is a rare condition that causes episodic hypertension due to a tumor in the adrenal glands. However, the patient does not have symptoms of episodic hypertension such as palpitations, sweating, or anxiety. This makes pheochromocytoma less likely. Cushing's syndrome, renal artery stenosis, and primary hyperaldosteronism can all cause hypertension. However, the patient does not have any symptoms or signs of these conditions such as a moon face, buffalo hump, or abdominal striae for Cushing's syndrome, or decreased kidney function for renal artery stenosis and primary hyperaldosteronism. Therefore, these conditions are less likely. The patient's hypertension is most likely due to her noncompliance with her antihypertensive medication. \n\nDiagnosis: Uncontrolled hypertension due to medication noncompliance.""
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10.1056/NEJMcpc1507212,Case 39-2015 — A 22-Year-Old Man with Hypoxemia and Shock,,Influenza A virus.,"Influenza with superimposed bacterial pneumonia, possibly due to Staphylococcus aureus or Streptococcus pneumoniae.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 22-year-old man was admitted to the intensive care unit of this hospital in the winter because of hypoxemia and shock.

The patient had been well until 5 days before admission, when head congestion, subjective fever, chills, and a nonproductive wet cough developed. He self-administered ibuprofen and acetaminophen, without improvement. One day before admission, he was seen in the emergency department of another hospital. On examination, the temperature was 37.3°C, the blood pressure 119/69 mm Hg, the pulse 97 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. Rales and wheezing were heard in the lungs, and the remainder of the examination was normal.

Figure 1.

Chest Radiographs Obtained at the Other Hospital.
Dr. Jo-Anne O. Shepard: A posteroanterior chest radiograph was clear (Figure 1A).

Dr. Lai: A diagnosis of bronchitis was made. Albuterol and ipratropium were administered by nebulizer, and a 4-day course of prednisone was begun. The patient’s symptoms reportedly improved, and he was discharged home with instructions to continue the prednisone course, begin therapy with an albuterol inhaler, and follow up with his physician.

Table 1.

Laboratory Data.
Approximately 24 hours later, relatives took the patient back to the emergency department of the other hospital because of cough, shortness of breath, diarrhea, diaphoresis, nausea, and vomiting; he reported no chest pain. On examination, he was in severe respiratory distress. The temperature was 36.8°C, the blood pressure 51/33 mm Hg, the pulse 165 beats per minute, the respiratory rate 55 breaths per minute, and the oxygen saturation 79% while he was breathing ambient air. His skin was ashen and mottled, and he had diffuse rales in both lungs; the abdomen was soft, and there were no cardiac murmurs or edema. Laboratory test results are shown in Table 1. A rapid influenza diagnostic test of a nasal swab was reportedly negative. Blood cultures were obtained. High-flow oxygen through a nonrebreather face mask and normal saline were administered. The oxygen saturation rose to 89% within minutes.

Dr. Shepard: A chest radiograph showed diffuse bilateral consolidations with some nodular opacification that were more prominent in the right lung than in the left lung; some had nodular contours. The size of the heart was normal, and no pleural fluid or pneumothorax was seen (Figure 1B).

Dr. Lai: An electrocardiogram revealed a ventricular rate of 161 beats per minute and was otherwise normal. A continuous infusion of norepinephrine was begun. Thirty minutes after the patient’s arrival at the other hospital, respiratory distress persisted, with labored breathing, nasal flaring, retractions, and diminished breath sounds throughout. Treatment with bilevel positive airway pressure was initiated, and the oxygen saturation rose to 100%; the respiratory rate was 12 breaths per minute, the blood pressure 102/85 mm Hg, the pulse 159 beats per minute, and the rectal temperature 40.7°C. Oseltamivir, piperacillin–tazobactam, levofloxacin, vancomycin, clindamycin, methylprednisolone, and ketorolac were administered. Three hours 10 minutes after the patient’s arrival, the oxygen saturation was 88% while he was receiving treatment with bilevel positive airway pressure. He was sedated, the trachea was intubated, and mechanical ventilation with positive end-expiratory pressure (PEEP) was begun. A triple-lumen central venous catheter was placed in the right internal jugular vein.

The patient was transported by medical helicopter to this hospital, arriving approximately 6 hours after his presentation at the other hospital. Additional history was obtained from family members. The patient had been well and was taking no medications until this illness developed. He had recently started spray painting buildings for work. He had no history of travel. He had visited the home of his adoptive parents the previous week; one relative had felt ill but the condition had since improved.

On examination, the patient was unresponsive and cold to the touch. He had poor capillary refill while he was receiving ventilatory support with high-flow oxygen at a rate of 30 breaths per minute, with a fraction of inspired oxygen of 1.0, a PEEP of 20 cm of water, and a tidal volume of 7 ml per kilogram of predicted body weight. He had intermittent agonal spontaneous breaths over the ventilated breaths, and the oxygen saturation was 82% while he was receiving ventilatory support. The temperature was 36.1°C, and the femoral pulses were 125 beats per minute; when measurements of systemic blood pressure were attempted, no reading could be obtained. The height was 180 cm, the weight 76.2 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 23.5. The lips were blue. The breath sounds were diminished bilaterally, with diffuse rhonchi and poor air movement. The heart sounds were distant and tachycardic, without murmurs. The skin was cool and poorly perfused; there was no peripheral edema, and the abdomen was soft. Bloody respiratory secretions were suctioned.

Blood levels of total and direct bilirubin, amylase, lactase, and alanine aminotransferase were normal; other test results are shown in Table 1. Urinalysis revealed amber cloudy urine, with a specific gravity of 1.013, 2+ occult blood, 1+ glucose, and 2+ albumin; the urine sediment showed 3 to 5 red cells and 5 to 10 white cells per high-power field, 10 to 20 hyaline casts and 5 to 10 granular casts per low-power field, squamous cells, and mucin. Toxicologic screening of the urine revealed cannabinoids; screening of the blood and urine for other toxins was negative. An electrocardiogram revealed sinus tachycardia.

The rate of infusion of norepinephrine was increased, and dobutamine and vasopressin were added. Sodium bicarbonate, fentanyl, versed, propofol, vecuronium bromide, vancomycin, cefepime, trimethoprim–sulfamethoxazole, levofloxacin, and phytonadione were administered. Platelets were transfused. An indwelling catheter was placed transcutaneously into the femoral artery. Transthoracic ultrasonography, which was performed at the bedside, revealed diffuse decreased cardiac function, a decreased ejection fraction, and no evidence of right ventricular enlargement or pericardial effusion; hypotension persisted. Four hours after the patient’s arrival at this hospital, extracorporeal membrane oxygenation (ECMO) was begun at the bedside.

Figure 2.

Chest Radiographs Obtained at This Hospital.
Dr. Shepard: A portable chest radiograph that was obtained shortly after the patient was admitted to this hospital showed slight, gradual progression in consolidations bilaterally and showed the placement of an endotracheal tube, a central venous catheter, and a nasogastric tube (Figure 2A). On a radiograph that was obtained 4 hours later, an ECMO catheter was present in the superior vena cava and other findings were unchanged (Figure 2B).

Dr. Lai: The patient was admitted to the intensive care unit. Diagnostic test results were received.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 22-year-old man was admitted to the intensive care unit of this hospital in the winter because of hypoxemia and shock.

The patient had been well until 5 days before admission, when head congestion, subjective fever, chills, and a nonproductive wet cough developed. He self-administered ibuprofen and acetaminophen, without improvement. One day before admission, he was seen in the emergency department of another hospital. On examination, the temperature was 37.3°C, the blood pressure 119/69 mm Hg, the pulse 97 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99% while he was breathing ambient air. Rales and wheezing were heard in the lungs, and the remainder of the examination was normal.

Figure 1.

Chest Radiographs Obtained at the Other Hospital.
Dr. Jo-Anne O. Shepard: A posteroanterior chest radiograph was clear (Figure 1A).

Dr. Lai: A diagnosis of bronchitis was made. Albuterol and ipratropium were administered by nebulizer, and a 4-day course of prednisone was begun. The patient’s symptoms reportedly improved, and he was discharged home with instructions to continue the prednisone course, begin therapy with an albuterol inhaler, and follow up with his physician.

Table 1.

Laboratory Data.
Approximately 24 hours later, relatives took the patient back to the emergency department of the other hospital because of cough, shortness of breath, diarrhea, diaphoresis, nausea, and vomiting; he reported no chest pain. On examination, he was in severe respiratory distress. The temperature was 36.8°C, the blood pressure 51/33 mm Hg, the pulse 165 beats per minute, the respiratory rate 55 breaths per minute, and the oxygen saturation 79% while he was breathing ambient air. His skin was ashen and mottled, and he had diffuse rales in both lungs; the abdomen was soft, and there were no cardiac murmurs or edema. Laboratory test results are shown in Table 1. A rapid influenza diagnostic test of a nasal swab was reportedly negative. Blood cultures were obtained. High-flow oxygen through a nonrebreather face mask and normal saline were administered. The oxygen saturation rose to 89% within minutes.

Dr. Shepard: A chest radiograph showed diffuse bilateral consolidations with some nodular opacification that were more prominent in the right lung than in the left lung; some had nodular contours. The size of the heart was normal, and no pleural fluid or pneumothorax was seen (Figure 1B).

Dr. Lai: An electrocardiogram revealed a ventricular rate of 161 beats per minute and was otherwise normal. A continuous infusion of norepinephrine was begun. Thirty minutes after the patient’s arrival at the other hospital, respiratory distress persisted, with labored breathing, nasal flaring, retractions, and diminished breath sounds throughout. Treatment with bilevel positive airway pressure was initiated, and the oxygen saturation rose to 100%; the respiratory rate was 12 breaths per minute, the blood pressure 102/85 mm Hg, the pulse 159 beats per minute, and the rectal temperature 40.7°C. Oseltamivir, piperacillin–tazobactam, levofloxacin, vancomycin, clindamycin, methylprednisolone, and ketorolac were administered. Three hours 10 minutes after the patient’s arrival, the oxygen saturation was 88% while he was receiving treatment with bilevel positive airway pressure. He was sedated, the trachea was intubated, and mechanical ventilation with positive end-expiratory pressure (PEEP) was begun. A triple-lumen central venous catheter was placed in the right internal jugular vein.

The patient was transported by medical helicopter to this hospital, arriving approximately 6 hours after his presentation at the other hospital. Additional history was obtained from family members. The patient had been well and was taking no medications until this illness developed. He had recently started spray painting buildings for work. He had no history of travel. He had visited the home of his adoptive parents the previous week; one relative had felt ill but the condition had since improved.

On examination, the patient was unresponsive and cold to the touch. He had poor capillary refill while he was receiving ventilatory support with high-flow oxygen at a rate of 30 breaths per minute, with a fraction of inspired oxygen of 1.0, a PEEP of 20 cm of water, and a tidal volume of 7 ml per kilogram of predicted body weight. He had intermittent agonal spontaneous breaths over the ventilated breaths, and the oxygen saturation was 82% while he was receiving ventilatory support. The temperature was 36.1°C, and the femoral pulses were 125 beats per minute; when measurements of systemic blood pressure were attempted, no reading could be obtained. The height was 180 cm, the weight 76.2 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 23.5. The lips were blue. The breath sounds were diminished bilaterally, with diffuse rhonchi and poor air movement. The heart sounds were distant and tachycardic, without murmurs. The skin was cool and poorly perfused; there was no peripheral edema, and the abdomen was soft. Bloody respiratory secretions were suctioned.

Blood levels of total and direct bilirubin, amylase, lactase, and alanine aminotransferase were normal; other test results are shown in Table 1. Urinalysis revealed amber cloudy urine, with a specific gravity of 1.013, 2+ occult blood, 1+ glucose, and 2+ albumin; the urine sediment showed 3 to 5 red cells and 5 to 10 white cells per high-power field, 10 to 20 hyaline casts and 5 to 10 granular casts per low-power field, squamous cells, and mucin. Toxicologic screening of the urine revealed cannabinoids; screening of the blood and urine for other toxins was negative. An electrocardiogram revealed sinus tachycardia.

The rate of infusion of norepinephrine was increased, and dobutamine and vasopressin were added. Sodium bicarbonate, fentanyl, versed, propofol, vecuronium bromide, vancomycin, cefepime, trimethoprim–sulfamethoxazole, levofloxacin, and phytonadione were administered. Platelets were transfused. An indwelling catheter was placed transcutaneously into the femoral artery. Transthoracic ultrasonography, which was performed at the bedside, revealed diffuse decreased cardiac function, a decreased ejection fraction, and no evidence of right ventricular enlargement or pericardial effusion; hypotension persisted. Four hours after the patient’s arrival at this hospital, extracorporeal membrane oxygenation (ECMO) was begun at the bedside.

Figure 2.

Chest Radiographs Obtained at This Hospital.
Dr. Shepard: A portable chest radiograph that was obtained shortly after the patient was admitted to this hospital showed slight, gradual progression in consolidations bilaterally and showed the placement of an endotracheal tube, a central venous catheter, and a nasogastric tube (Figure 2A). On a radiograph that was obtained 4 hours later, an ECMO catheter was present in the superior vena cava and other findings were unchanged (Figure 2B).

Dr. Lai: The patient was admitted to the intensive care unit. Diagnostic test results were received.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presented with symptoms of a respiratory infection, including head congestion, fever, chills, and a nonproductive wet cough. His condition rapidly deteriorated, leading to severe respiratory distress and shock. Despite the administration of broad-spectrum antibiotics, his condition did not improve, suggesting that the cause of his symptoms was not a bacterial infection. The patient's recent history of spray painting buildings for work suggests exposure to chemical toxins, which can cause acute respiratory distress syndrome (ARDS). The chest radiographs showing diffuse bilateral consolidations and the presence of bloody respiratory secretions further support the diagnosis of ARDS. \n\nAcute Respiratory Distress Syndrome (ARDS) is the most likely diagnosis.""
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        ""content"": ""The patient is a young man who presents with hypoxemia and shock, with symptoms of head congestion, fever, chills, and a nonproductive wet cough. He also has diarrhea, diaphoresis, nausea, and vomiting. His symptoms worsened over a period of 5 days. The differential diagnosis for this patient includes pneumonia, sepsis, acute respiratory distress syndrome (ARDS), and influenza. The patient's chest radiograph shows diffuse bilateral consolidations, which is consistent with pneumonia or ARDS. His rapid influenza diagnostic test was negative, making influenza less likely. The patient's severe hypoxemia and shock, along with his rapid deterioration, are suggestive of sepsis. However, his blood cultures were not reported to be positive, which makes a bacterial infection less likely. The patient's recent history of starting work as a spray painter could suggest an inhalation injury leading to ARDS. However, his symptoms started 5 days before admission, which is a relatively long incubation period for an inhalation injury. Given the patient's severe hypoxemia, diffuse bilateral consolidations on chest radiograph, and rapid deterioration, ARDS is the most likely diagnosis.\n\nDiagnosis: Acute Respiratory Distress Syndrome (ARDS)""
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10.1056/NEJMcpc1506821,Case 38-2015 — A 21-Year-Old Man with Fatigue and Weight Loss,,"Metastatic choriocarcinoma involving the liver.

Testicular teratoma with a focus of calcification consistent with a regressed germ-cell tumor.",Metastatic nonseminomatous germ-cell tumor (with prominent choriocarcinoma elements) causing hCG-mediated hyperthyroidism and gynecomastia.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 21-year-old man was admitted to this hospital because of fatigue, weight loss, and lesions in the lungs and liver on radiographic imaging.

The patient had been in excellent health, running 3 to 5 miles daily and competing in sports, until approximately 3 months before this admission, when increasing fatigue occurred. During the next 6 weeks, his sleep requirement increased from 8 to 20 hours per day. Approximately 2 months before this admission, he was a passenger in a motor vehicle accident, after which he had an exacerbation of chronic back pain that he had previously attributed to sports activities. He was seen in a clinic of another hospital a few days later; a radiograph of the cervical spine was normal. He took nonsteroidal antiinflammatory drugs as needed for pain. One week later, he went to the emergency department of a second hospital because of fatigue, low back pain, and bilateral swelling of the breast tissue. Testing for Lyme disease was negative. He was advised to discontinue taking the workout supplements (which contained creatine nitrate) that he had been taking for several years. The next week, he returned to the second hospital because of worsening symptoms; test results were reportedly unchanged. A muscle relaxant was administered, without improvement.

Table 1.

Laboratory Data.
One month before this admission, anorexia, nausea, nonbilious nonbloody vomiting, weight loss, intermittent chills, and anxiety occurred, followed by dyspnea with exertion and decreased exercise tolerance (i.e., exercise was limited to walking several blocks before resting). On evaluation in the emergency department of the second hospital 3 weeks before this admission, testing for Lyme disease was negative; other test results are shown in Table 1. The stool was positive for occult blood, and urinalysis revealed trace protein, increased urobilinogen (2.0; reference range, 0.0 to 1.0), and 9 red cells per high-power field (reference range, 0 to 5). Diagnoses of anemia and hyperthyroidism were made. The patient was discharged with instructions to see a gastroenterologist and an endocrinologist.

The next day, on evaluation in a gastroenterology clinic, the patient reported fatigue, weight loss of 6 kg (from 82 kg to 76 kg), and hematochezia. The body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 21.6. There was abdominal guarding and tenderness in the right lower quadrant, with no hepatomegaly or splenomegaly. The stool was brown, with occult blood. Four days later, upper and lower endoscopic examinations revealed no active bleeding. Pathological examination of bowel-biopsy specimens was reportedly normal. Ten days later (6 days before this admission), the patient was evaluated by an endocrinologist. Thyroid scintigraphy reportedly showed elevated and diffuse uptake of radioactive iodine. Therapy with methimazole and propranolol was begun.

Two days before this admission, on return to the gastroenterology clinic, the patient reported persistent symptoms, as well as cough, sweats, nocturia, dark urine, and intermittent tremors. The temperature was normal, the blood pressure 118/50 mm Hg, the pulse 100 beats per minute, and the BMI 20.0. Wasting of the facial muscle was noted. The stool was positive for occult blood. Therapy with ondansetron was begun. The next day, the blood level of vitamin B12 was normal; other test results are shown in Table 1. Computed tomography (CT) of the abdomen and pelvis, performed at the second hospital with the administration of oral contrast material, revealed numerous pulmonary masses (up to 4 cm in diameter) at the lung bases, hepatomegaly with lesions in the liver (up to 13 cm by 9 cm), massive retroperitoneal lymphadenopathy, and gynecomastia. Because of these findings and at the request of his family, the patient was referred to this hospital.

On presentation, the patient reported fatigue and anxiety, both of which had improved after treatment with methimazole and propranolol. He also reported persistent nausea, vomiting, abdominal discomfort (which he rated at 3 on a scale of 0 to 10, with 10 indicating the most severe discomfort), dyspnea, and weight loss of 14 kg in the previous 2.5 weeks. Four years earlier, he had had methicillin-resistant Staphylococcus aureus preseptal cellulitis after trauma above his right eye. Medications were methimazole, propranolol, and ondansetron. He had no known allergies. He lived with his family, attended college, and had jobs during vacation. He had chewed tobacco and drunk alcohol but had stopped doing both 1 month before this admission; he reported no use of intravenous illicit drugs. His mother had Graves’ disease, his father had hypothyroidism and hypertension, his maternal grandmother had diabetes mellitus, and his siblings were healthy.

On examination, the patient appeared to be fatigued. The vital signs were normal, and the oxygen saturation was 100% while he was breathing ambient air. There was tender gynecomastia and inguinal lymphadenopathy on the right side; the right testicle was larger than the left, without tenderness or fluctuance. Hepatomegaly to the umbilicus was present. The remainder of the examination was normal, with no splenomegaly or palpable lymphadenopathy. The activated partial-thromboplastin time and plasma lactic acid level were normal, as were blood levels of glucose, total protein, albumin, globulin, phosphorus, magnesium, calcium, alanine aminotransferase, amylase, and lipase and results of renal-function tests; other test results are shown in Table 1. Additional imaging studies were obtained.

Figure 1.

CT Scans of the Chest, Abdomen, and Pelvis.
Dr. Micheal McInnis: A chest radiograph showed bilateral, well-circumscribed pulmonary nodules and masses. Contrast-enhanced CT scans of the chest, abdomen, and pelvis showed bilateral pulmonary nodules and masses, with the greatest distribution in the lower lung zones (Figure 1A). No notable mediastinal or hilar lymphadenopathy was present. Bilateral, symmetric gynecomastia was observed (Figure 1B). Multiple heterogeneous masses, measuring up to 11 cm in longest transverse dimension, were distributed throughout the liver (Figure 1C). A necrotic retroperitoneal nodal mass was observed in the interaortocaval position, below the level of the renal hila (Figure 1D). The third and fourth segments of the duodenum were compressed and displaced anteriorly by the retroperitoneal nodal mass. No other notable retroperitoneal lymphadenopathy was present. The remaining organs of the abdomen and pelvis were unremarkable. Ultrasonography of the scrotum revealed an area of calcification (3 mm by 4 mm by 2 mm) in the right lower testicle; the right testis was 4.0 cm by 2.8 cm by 2.1 cm, and the left testis was 3.7 cm by 2.6 cm by 2.0 cm.

Dr. Hundemer: The patient was admitted to this hospital, and diagnostic procedures were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 21-year-old man was admitted to this hospital because of fatigue, weight loss, and lesions in the lungs and liver on radiographic imaging.

The patient had been in excellent health, running 3 to 5 miles daily and competing in sports, until approximately 3 months before this admission, when increasing fatigue occurred. During the next 6 weeks, his sleep requirement increased from 8 to 20 hours per day. Approximately 2 months before this admission, he was a passenger in a motor vehicle accident, after which he had an exacerbation of chronic back pain that he had previously attributed to sports activities. He was seen in a clinic of another hospital a few days later; a radiograph of the cervical spine was normal. He took nonsteroidal antiinflammatory drugs as needed for pain. One week later, he went to the emergency department of a second hospital because of fatigue, low back pain, and bilateral swelling of the breast tissue. Testing for Lyme disease was negative. He was advised to discontinue taking the workout supplements (which contained creatine nitrate) that he had been taking for several years. The next week, he returned to the second hospital because of worsening symptoms; test results were reportedly unchanged. A muscle relaxant was administered, without improvement.

Table 1.

Laboratory Data.
One month before this admission, anorexia, nausea, nonbilious nonbloody vomiting, weight loss, intermittent chills, and anxiety occurred, followed by dyspnea with exertion and decreased exercise tolerance (i.e., exercise was limited to walking several blocks before resting). On evaluation in the emergency department of the second hospital 3 weeks before this admission, testing for Lyme disease was negative; other test results are shown in Table 1. The stool was positive for occult blood, and urinalysis revealed trace protein, increased urobilinogen (2.0; reference range, 0.0 to 1.0), and 9 red cells per high-power field (reference range, 0 to 5). Diagnoses of anemia and hyperthyroidism were made. The patient was discharged with instructions to see a gastroenterologist and an endocrinologist.

The next day, on evaluation in a gastroenterology clinic, the patient reported fatigue, weight loss of 6 kg (from 82 kg to 76 kg), and hematochezia. The body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 21.6. There was abdominal guarding and tenderness in the right lower quadrant, with no hepatomegaly or splenomegaly. The stool was brown, with occult blood. Four days later, upper and lower endoscopic examinations revealed no active bleeding. Pathological examination of bowel-biopsy specimens was reportedly normal. Ten days later (6 days before this admission), the patient was evaluated by an endocrinologist. Thyroid scintigraphy reportedly showed elevated and diffuse uptake of radioactive iodine. Therapy with methimazole and propranolol was begun.

Two days before this admission, on return to the gastroenterology clinic, the patient reported persistent symptoms, as well as cough, sweats, nocturia, dark urine, and intermittent tremors. The temperature was normal, the blood pressure 118/50 mm Hg, the pulse 100 beats per minute, and the BMI 20.0. Wasting of the facial muscle was noted. The stool was positive for occult blood. Therapy with ondansetron was begun. The next day, the blood level of vitamin B12 was normal; other test results are shown in Table 1. Computed tomography (CT) of the abdomen and pelvis, performed at the second hospital with the administration of oral contrast material, revealed numerous pulmonary masses (up to 4 cm in diameter) at the lung bases, hepatomegaly with lesions in the liver (up to 13 cm by 9 cm), massive retroperitoneal lymphadenopathy, and gynecomastia. Because of these findings and at the request of his family, the patient was referred to this hospital.

On presentation, the patient reported fatigue and anxiety, both of which had improved after treatment with methimazole and propranolol. He also reported persistent nausea, vomiting, abdominal discomfort (which he rated at 3 on a scale of 0 to 10, with 10 indicating the most severe discomfort), dyspnea, and weight loss of 14 kg in the previous 2.5 weeks. Four years earlier, he had had methicillin-resistant Staphylococcus aureus preseptal cellulitis after trauma above his right eye. Medications were methimazole, propranolol, and ondansetron. He had no known allergies. He lived with his family, attended college, and had jobs during vacation. He had chewed tobacco and drunk alcohol but had stopped doing both 1 month before this admission; he reported no use of intravenous illicit drugs. His mother had Graves’ disease, his father had hypothyroidism and hypertension, his maternal grandmother had diabetes mellitus, and his siblings were healthy.

On examination, the patient appeared to be fatigued. The vital signs were normal, and the oxygen saturation was 100% while he was breathing ambient air. There was tender gynecomastia and inguinal lymphadenopathy on the right side; the right testicle was larger than the left, without tenderness or fluctuance. Hepatomegaly to the umbilicus was present. The remainder of the examination was normal, with no splenomegaly or palpable lymphadenopathy. The activated partial-thromboplastin time and plasma lactic acid level were normal, as were blood levels of glucose, total protein, albumin, globulin, phosphorus, magnesium, calcium, alanine aminotransferase, amylase, and lipase and results of renal-function tests; other test results are shown in Table 1. Additional imaging studies were obtained.

Figure 1.

CT Scans of the Chest, Abdomen, and Pelvis.
Dr. Micheal McInnis: A chest radiograph showed bilateral, well-circumscribed pulmonary nodules and masses. Contrast-enhanced CT scans of the chest, abdomen, and pelvis showed bilateral pulmonary nodules and masses, with the greatest distribution in the lower lung zones (Figure 1A). No notable mediastinal or hilar lymphadenopathy was present. Bilateral, symmetric gynecomastia was observed (Figure 1B). Multiple heterogeneous masses, measuring up to 11 cm in longest transverse dimension, were distributed throughout the liver (Figure 1C). A necrotic retroperitoneal nodal mass was observed in the interaortocaval position, below the level of the renal hila (Figure 1D). The third and fourth segments of the duodenum were compressed and displaced anteriorly by the retroperitoneal nodal mass. No other notable retroperitoneal lymphadenopathy was present. The remaining organs of the abdomen and pelvis were unremarkable. Ultrasonography of the scrotum revealed an area of calcification (3 mm by 4 mm by 2 mm) in the right lower testicle; the right testis was 4.0 cm by 2.8 cm by 2.1 cm, and the left testis was 3.7 cm by 2.6 cm by 2.0 cm.

Dr. Hundemer: The patient was admitted to this hospital, and diagnostic procedures were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Testicular cancer with metastasis to the lungs and liver. The patient's symptoms of fatigue, weight loss, and the presence of lesions in the lungs and liver on radiographic imaging are indicative of a systemic disease. The presence of gynecomastia and a larger right testicle suggests a testicular abnormality, which could be cancerous. The presence of pulmonary nodules and masses, as well as multiple heterogeneous masses in the liver, suggests metastasis from a primary cancer site. The presence of calcification in the right testicle further supports the diagnosis of testicular cancer.""
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        ""content"": ""The patient's symptoms of fatigue, weight loss, and the presence of lesions in the lungs and liver on radiographic imaging suggest a systemic disease. The presence of gynecomastia and a larger right testicle suggest hormonal imbalance or a testicular issue. The presence of pulmonary masses, hepatomegaly with lesions in the liver, and retroperitoneal lymphadenopathy on CT scan suggest a malignancy. The absence of splenomegaly or palpable lymphadenopathy and normal blood levels of glucose, total protein, albumin, globulin, phosphorus, magnesium, calcium, alanine aminotransferase, amylase, and lipase and results of renal-function tests suggest that the malignancy is not lymphoma or leukemia. The presence of an area of calcification in the right lower testicle on ultrasonography suggests a testicular tumor. Testicular tumors can secrete hormones, which could explain the gynecomastia. Testicular tumors can also metastasize to the lungs and liver, which would explain the pulmonary masses and liver lesions. \n\nDiagnosis: Metastatic testicular cancer.""
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        ""content"": ""The patient is a young man who presents with fatigue, weight loss, and lesions in the lungs and liver. He also has gynecomastia, hepatomegaly, and inguinal lymphadenopathy. The differential diagnosis for this patient includes lymphoma, testicular cancer, and liver cancer. The patient's symptoms of fatigue and weight loss, along with the presence of lesions in the lungs and liver, are suggestive of a systemic malignancy. The presence of gynecomastia and a larger right testicle could suggest testicular cancer, which can secrete hormones leading to gynecomastia. However, the ultrasound of the scrotum only revealed a small area of calcification, which is not typical of testicular cancer. The presence of hepatomegaly and lesions in the liver could suggest liver cancer, but this would not explain the gynecomastia or the lesions in the lungs. The presence of inguinal lymphadenopathy, along with the systemic symptoms and the lesions in the lungs and liver, is most suggestive of lymphoma. This could be a systemic disease that is affecting multiple organ systems, leading to the patient's symptoms and the findings on imaging.\n\nDiagnosis: Lymphoma is the most likely diagnosis.""
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 10.1056/NEJMcpc1504839,"Case 37-2015 — A 76-Year-Old Man with Fevers, Leukopenia, and Pulmonary Infiltrates",,Disseminated Mycobacterium bovis infection.,Tuberculosis (due to Mycobacterium bovis) after intravesicular therapy with bacille Calmette–Guérin.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 76-year-old man with multiple medical problems was admitted to this hospital because of persistent fever, leukopenia, and pulmonary infiltrates.

The patient had been generally well until approximately 5 weeks before this admission, when fever (to a temperature of 38.9°C), chills, cough, night sweats, diarrhea, fatigue, weakness, and anorexia occurred. Four weeks before this admission, he was seen by his physician, who noted that he had had a weight loss of 5 kg in the previous 7 months. Urinalysis and cultures of urine and blood were reportedly negative. A chest radiograph and computed tomographic (CT) scan of the abdomen and pelvis, obtained without the administration of contrast material, were reportedly negative and were not available for review. The diarrhea resolved, but other symptoms persisted. Three weeks before this admission, CT of the chest reportedly revealed diffuse symmetric fine interstitial reticular lung nodularities, small pleural effusions, and mild splenomegaly.

Two days later, the patient fell because of profound weakness and was admitted to another hospital. He had hypertension, hyperlipidemia, chronic obstructive pulmonary disease, coronary artery disease (with previous bypass grafting), congestive heart failure, peripheral vascular disease (with previous aortofemoral bypass surgery), non–insulin-dependent diabetes mellitus, gout, and benign prostatic hypertrophy. He also had transitional-cell carcinoma of the bladder that was in remission after treatment including bacille Calmette–Guérin (BCG) therapy, which had most recently been administered 7 months earlier. Medications taken at home were sitagliptin, metformin, lisinopril, atorvastatin, atenolol, clopidogrel, finasteride, dutasteride, terazosin, allopurinol, citalopram, folate, a multivitamin, and ipratropium–albuterol (by inhalation).

Table 1.

Laboratory Data.
Figure 1.

Chest Radiographs.
On examination, the temperature was 39.9°C, the blood pressure 110/82 mm Hg, the pulse 86 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 93% while the patient was breathing ambient air and 97% while he was breathing oxygen through a nasal cannula at a rate of 2 liters per minute. There was abdominal distention, with tenderness in the right upper quadrant. Results of coagulation tests and blood levels of total and direct bilirubin were normal; other test results are shown in Table 1. Abdominal ultrasonography revealed a horseshoe kidney and a mildly heterogeneous liver. A chest radiograph showed a patchy opacity in the right midzone (Figure 1A). Transthoracic echocardiography reportedly revealed no evidence of endocarditis. During the first week, testing was negative for influenza antigen, as well as for human immunodeficiency virus (HIV), Epstein–Barr virus, cytomegalovirus, Borrelia burgdorferi, ehrlichia, Anaplasma phagocytophilum, babesia, rickettsia (Rocky Mountain spotted fever), parvovirus, and hepatitis A, B, and C viruses. Cultures of the blood and urine were negative. Pathological examination of a bone marrow–biopsy specimen and aspirate, which was performed because of the pancytopenia, was normal. Diffuse bilateral interstitial pulmonary edema developed; fluid was restricted, and furosemide administered.

Dr. Shaunagh McDermott: On the fifth day, a chest radiograph showed a persistent patchy opacity in the right midzone and diffuse reticular opacities in the lung bases (Figure 1B). The next day, a CT scan of the chest showed diffuse ground-glass opacities throughout both lungs; the ground-glass opacities in the dependent lower lobes were more confluent. There were also small bilateral pleural effusions.

Dr. Danford: Laboratory test results are shown in Table 1. On the 9th day, hemoptysis occurred, the temperature rose to 39.1°C, and the oxygen saturation decreased to 89% while the patient was breathing oxygen through a nasal cannula at a rate of 1 liter per minute. The rate of oxygen supplementation was increased to 3 liters per minute. Bronchoalveolar lavage reportedly revealed no evidence of diffuse alveolar hemorrhage or malignant cells; cultures of the lavage fluid were negative. After consultation with a rheumatologist, methylprednisolone (1 g daily) was administered for 3 days, followed by prednisone (60 mg daily). The fevers initially improved but then recurred. On the 15th day, video-assisted thoracic surgery was performed. Pathological examination of a lung-biopsy specimen reportedly revealed extensive noncaseating granulomatous inflammation and granulomas in both bronchiolocentric and lymphangitic distributions. On the 18th day, hemoptysis recurred, and the oxygen saturation decreased to 86% while the patient was at rest and breathing ambient air.

Figure 2.

Chest CT Scans.
Dr. McDermott: A second CT scan of the chest (Figure 2) revealed persistent diffuse ground-glass opacities with subpleural reticulations in the lower lobes bilaterally; these findings were now visible because of the decrease in size of the bilateral pleural effusions. There was evidence of wedge resections of the right upper and lower lobes and subcutaneous emphysema.

Dr. Danford: Vancomycin and piperacillin–tazobactam were administered. The day before this admission, confusion developed, with associated myoclonus during sleep and a temperature of 38.9°C. Lumbar puncture and CT and magnetic resonance imaging (MRI) of the head were performed; the studies revealed atrophy but no evidence of acute infarction, hemorrhage, or space-occupying masses. The dose of glucocorticoid therapy was decreased. On the 22nd day, a chest radiograph showed a persistent opacity in the right midzone and subcutaneous emphysema. Ethambutol, rifampin, and isoniazid were administered. Laboratory test results are shown in Table 1. The patient was transferred and admitted to this hospital.

The patient was allergic to contrast dye. He lived alone and had retired from the construction industry, with past exposure to asbestos. He had a 46-pack-year history of smoking and had stopped 10 years earlier; he had stopped drinking alcohol 20 years earlier and did not use illicit drugs. He had traveled to Mexico in the remote past. His son, who lived nearby, owned chickens. He was a hunter and had had exposures to deer, rabbits, and pheasants in the previous 5 months. His father and brother may have had rheumatoid arthritis.

On examination, the patient appeared to be mildly uncomfortable and was flushed. The respiratory rate was 18 breaths per minute, and the oxygen saturation 93% while he was breathing ambient air; the other vital signs were normal. He had shallow ulcerations on the right side of the hard palate, crackles in both lung bases, occasional expiratory wheezes, and trace ankle edema on the left side. The remainder of the examination was normal. Results of coagulation tests and blood levels of phosphorus and total and direct bilirubin were normal; testing for antibodies to the Goodpasture antigen was negative, as were the results of a lung panel for hypersensitivity pneumonitis. Other test results are shown in Table 1. Antibiotic agents and glucocorticoids were not administered. On the third day, a diagnostic test was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 76-year-old man with multiple medical problems was admitted to this hospital because of persistent fever, leukopenia, and pulmonary infiltrates.

The patient had been generally well until approximately 5 weeks before this admission, when fever (to a temperature of 38.9°C), chills, cough, night sweats, diarrhea, fatigue, weakness, and anorexia occurred. Four weeks before this admission, he was seen by his physician, who noted that he had had a weight loss of 5 kg in the previous 7 months. Urinalysis and cultures of urine and blood were reportedly negative. A chest radiograph and computed tomographic (CT) scan of the abdomen and pelvis, obtained without the administration of contrast material, were reportedly negative and were not available for review. The diarrhea resolved, but other symptoms persisted. Three weeks before this admission, CT of the chest reportedly revealed diffuse symmetric fine interstitial reticular lung nodularities, small pleural effusions, and mild splenomegaly.

Two days later, the patient fell because of profound weakness and was admitted to another hospital. He had hypertension, hyperlipidemia, chronic obstructive pulmonary disease, coronary artery disease (with previous bypass grafting), congestive heart failure, peripheral vascular disease (with previous aortofemoral bypass surgery), non–insulin-dependent diabetes mellitus, gout, and benign prostatic hypertrophy. He also had transitional-cell carcinoma of the bladder that was in remission after treatment including bacille Calmette–Guérin (BCG) therapy, which had most recently been administered 7 months earlier. Medications taken at home were sitagliptin, metformin, lisinopril, atorvastatin, atenolol, clopidogrel, finasteride, dutasteride, terazosin, allopurinol, citalopram, folate, a multivitamin, and ipratropium–albuterol (by inhalation).

Table 1.

Laboratory Data.
Figure 1.

Chest Radiographs.
On examination, the temperature was 39.9°C, the blood pressure 110/82 mm Hg, the pulse 86 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 93% while the patient was breathing ambient air and 97% while he was breathing oxygen through a nasal cannula at a rate of 2 liters per minute. There was abdominal distention, with tenderness in the right upper quadrant. Results of coagulation tests and blood levels of total and direct bilirubin were normal; other test results are shown in Table 1. Abdominal ultrasonography revealed a horseshoe kidney and a mildly heterogeneous liver. A chest radiograph showed a patchy opacity in the right midzone (Figure 1A). Transthoracic echocardiography reportedly revealed no evidence of endocarditis. During the first week, testing was negative for influenza antigen, as well as for human immunodeficiency virus (HIV), Epstein–Barr virus, cytomegalovirus, Borrelia burgdorferi, ehrlichia, Anaplasma phagocytophilum, babesia, rickettsia (Rocky Mountain spotted fever), parvovirus, and hepatitis A, B, and C viruses. Cultures of the blood and urine were negative. Pathological examination of a bone marrow–biopsy specimen and aspirate, which was performed because of the pancytopenia, was normal. Diffuse bilateral interstitial pulmonary edema developed; fluid was restricted, and furosemide administered.

Dr. Shaunagh McDermott: On the fifth day, a chest radiograph showed a persistent patchy opacity in the right midzone and diffuse reticular opacities in the lung bases (Figure 1B). The next day, a CT scan of the chest showed diffuse ground-glass opacities throughout both lungs; the ground-glass opacities in the dependent lower lobes were more confluent. There were also small bilateral pleural effusions.

Dr. Danford: Laboratory test results are shown in Table 1. On the 9th day, hemoptysis occurred, the temperature rose to 39.1°C, and the oxygen saturation decreased to 89% while the patient was breathing oxygen through a nasal cannula at a rate of 1 liter per minute. The rate of oxygen supplementation was increased to 3 liters per minute. Bronchoalveolar lavage reportedly revealed no evidence of diffuse alveolar hemorrhage or malignant cells; cultures of the lavage fluid were negative. After consultation with a rheumatologist, methylprednisolone (1 g daily) was administered for 3 days, followed by prednisone (60 mg daily). The fevers initially improved but then recurred. On the 15th day, video-assisted thoracic surgery was performed. Pathological examination of a lung-biopsy specimen reportedly revealed extensive noncaseating granulomatous inflammation and granulomas in both bronchiolocentric and lymphangitic distributions. On the 18th day, hemoptysis recurred, and the oxygen saturation decreased to 86% while the patient was at rest and breathing ambient air.

Figure 2.

Chest CT Scans.
Dr. McDermott: A second CT scan of the chest (Figure 2) revealed persistent diffuse ground-glass opacities with subpleural reticulations in the lower lobes bilaterally; these findings were now visible because of the decrease in size of the bilateral pleural effusions. There was evidence of wedge resections of the right upper and lower lobes and subcutaneous emphysema.

Dr. Danford: Vancomycin and piperacillin–tazobactam were administered. The day before this admission, confusion developed, with associated myoclonus during sleep and a temperature of 38.9°C. Lumbar puncture and CT and magnetic resonance imaging (MRI) of the head were performed; the studies revealed atrophy but no evidence of acute infarction, hemorrhage, or space-occupying masses. The dose of glucocorticoid therapy was decreased. On the 22nd day, a chest radiograph showed a persistent opacity in the right midzone and subcutaneous emphysema. Ethambutol, rifampin, and isoniazid were administered. Laboratory test results are shown in Table 1. The patient was transferred and admitted to this hospital.

The patient was allergic to contrast dye. He lived alone and had retired from the construction industry, with past exposure to asbestos. He had a 46-pack-year history of smoking and had stopped 10 years earlier; he had stopped drinking alcohol 20 years earlier and did not use illicit drugs. He had traveled to Mexico in the remote past. His son, who lived nearby, owned chickens. He was a hunter and had had exposures to deer, rabbits, and pheasants in the previous 5 months. His father and brother may have had rheumatoid arthritis.

On examination, the patient appeared to be mildly uncomfortable and was flushed. The respiratory rate was 18 breaths per minute, and the oxygen saturation 93% while he was breathing ambient air; the other vital signs were normal. He had shallow ulcerations on the right side of the hard palate, crackles in both lung bases, occasional expiratory wheezes, and trace ankle edema on the left side. The remainder of the examination was normal. Results of coagulation tests and blood levels of phosphorus and total and direct bilirubin were normal; testing for antibodies to the Goodpasture antigen was negative, as were the results of a lung panel for hypersensitivity pneumonitis. Other test results are shown in Table 1. Antibiotic agents and glucocorticoids were not administered. On the third day, a diagnostic test was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Disseminated Mycobacterium bovis infection following intravesical BCG therapy. The patient's history of transitional-cell carcinoma of the bladder treated with BCG therapy, along with his symptoms of persistent fever, leukopenia, and pulmonary infiltrates, suggest a systemic infection. The granulomatous inflammation seen in the lung biopsy is consistent with mycobacterial infection. The negative cultures do not rule out mycobacterial infection, as these organisms are slow-growing and may not be detected in standard cultures. The patient's lack of response to broad-spectrum antibiotics further supports the diagnosis of a mycobacterial infection.""
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        ""content"": ""The patient's history of transitional-cell carcinoma of the bladder treated with BCG therapy, along with his symptoms of persistent fever, leukopenia, and pulmonary infiltrates, suggest a disseminated BCG infection. This is further supported by the finding of noncaseating granulomas in the lung biopsy, which is consistent with mycobacterial infection. The patient's lack of response to broad-spectrum antibiotics and steroids also suggests an atypical infection such as mycobacterium. \n\nDiagnosis: Disseminated BCG infection.""
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        ""content"": ""This is a 76-year-old man with a history of multiple medical problems including transitional-cell carcinoma of the bladder treated with BCG therapy, who presents with persistent fever, leukopenia, and pulmonary infiltrates. His symptoms include fever, chills, cough, night sweats, diarrhea, fatigue, weakness, and anorexia. He also has a history of weight loss. His chest CT shows diffuse symmetric fine interstitial reticular lung nodularities, small pleural effusions, and mild splenomegaly. His lab results show leukopenia. The differential diagnosis for this patient includes infection, malignancy, and autoimmune disease. Given his history of BCG therapy for bladder cancer, one possibility is BCG infection. However, his cultures are negative, making this less likely. His symptoms and imaging findings could also be consistent with a malignancy such as lymphoma or a recurrence of his bladder cancer. However, his bone marrow biopsy was normal, making this less likely. His symptoms and imaging findings could also be consistent with an autoimmune disease such as vasculitis or sarcoidosis. Given his history of possible family history of rheumatoid arthritis, this could be a possibility. However, his rheumatologic workup was negative. His lung biopsy showed noncaseating granulomas, which is a hallmark of sarcoidosis. Given his clinical presentation, imaging findings, and biopsy results, sarcoidosis is the most likely diagnosis.\n\nDiagnosis: Sarcoidosis.""
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10.1056/NEJMcpc1410941,Case 36-2015 — A 27-Year-Old Woman with a Lesion of the Ear Canal,,Epithelioid hemangioma.,Epithelioid hemangioma.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 27-year-old woman was seen in an outpatient otolaryngology clinic of the Massachusetts Eye and Ear Infirmary, which is affiliated with this hospital, because of a pruritic lesion of the left ear canal, with recurrent bleeding.

One year before this presentation, a ballooning lesion had developed in the patient’s left ear canal that partially occluded the lumen and was associated with pruritus and recurrent bleeding. An unknown medication was administered topically into the ear canal, with improvement in both bleeding and pruritus. Two weeks before this presentation, bleeding from the left ear canal recurred, with associated pruritus of both ear canals. The patient was seen by a physician at another clinic, who prescribed an otic suspension (consisting of neomycin, polymyxin B sulfate, and hydrocortisone) and a 5-day course of oral azithromycin, as well as topical clobetasol propionate ointment (0.05%) for pruritus; the symptoms did not improve, and the bleeding did not resolve. She was referred to the outpatient otolaryngology clinic of the Massachusetts Eye and Ear Infirmary.

The patient reported brief episodes of sharp, stabbing otalgia on the left side, with episodes of disequilibrium that lasted for a few seconds and were not associated with vertigo, tinnitus, or changes in hearing. She had not had recurrent otitis media during childhood, exposure to loud noises, or head trauma with loss of consciousness. She took no other medications and had no known allergies. She worked in a health-related field. She did not smoke or drink alcohol.

On examination, the patient appeared to be well, with no craniofacial dysmorphism. A light pink raised lesion (approximately 1.0 cm by 1.0 cm by 0.5 cm), with a cobblestone appearance and several prominent vessels, was present on the posterior tragus of the left ear; on examination with an operating microscope, the lesion extended medially along the anterior wall of the external auditory canal. The eardrums, medial left ear canal, and entire right ear canal were normal. There was no tragal tenderness. A 512-Hz tuning fork was used to show that the Rinne test was positive bilaterally (with air conduction greater than bone conduction) and that, on the Weber test, the sound was located along the midline. The remainder of the examination of the nose, nasopharynx, mouth, pharynx, larynx, neck, ears (for hearing acuity for conversational speech), and third through twelfth cranial nerves was normal, and there was no spontaneous nystagmus. A culture of the left external ear canal grew a moderate amount of coagulase-negative staphylococcus species. Topical nystatin–triamcinolone ointment was administered to the left ear twice daily for 2 weeks, without improvement.

One week later, the patient returned to the outpatient clinic. She reported near constant pruritus and bleeding that had increased in amount and frequency. The lesion in the left ear canal appeared to be unchanged from the previous examination. A small crust covered the most medial aspect of the lesion.

Nine days later, a diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 27-year-old woman was seen in an outpatient otolaryngology clinic of the Massachusetts Eye and Ear Infirmary, which is affiliated with this hospital, because of a pruritic lesion of the left ear canal, with recurrent bleeding.

One year before this presentation, a ballooning lesion had developed in the patient’s left ear canal that partially occluded the lumen and was associated with pruritus and recurrent bleeding. An unknown medication was administered topically into the ear canal, with improvement in both bleeding and pruritus. Two weeks before this presentation, bleeding from the left ear canal recurred, with associated pruritus of both ear canals. The patient was seen by a physician at another clinic, who prescribed an otic suspension (consisting of neomycin, polymyxin B sulfate, and hydrocortisone) and a 5-day course of oral azithromycin, as well as topical clobetasol propionate ointment (0.05%) for pruritus; the symptoms did not improve, and the bleeding did not resolve. She was referred to the outpatient otolaryngology clinic of the Massachusetts Eye and Ear Infirmary.

The patient reported brief episodes of sharp, stabbing otalgia on the left side, with episodes of disequilibrium that lasted for a few seconds and were not associated with vertigo, tinnitus, or changes in hearing. She had not had recurrent otitis media during childhood, exposure to loud noises, or head trauma with loss of consciousness. She took no other medications and had no known allergies. She worked in a health-related field. She did not smoke or drink alcohol.

On examination, the patient appeared to be well, with no craniofacial dysmorphism. A light pink raised lesion (approximately 1.0 cm by 1.0 cm by 0.5 cm), with a cobblestone appearance and several prominent vessels, was present on the posterior tragus of the left ear; on examination with an operating microscope, the lesion extended medially along the anterior wall of the external auditory canal. The eardrums, medial left ear canal, and entire right ear canal were normal. There was no tragal tenderness. A 512-Hz tuning fork was used to show that the Rinne test was positive bilaterally (with air conduction greater than bone conduction) and that, on the Weber test, the sound was located along the midline. The remainder of the examination of the nose, nasopharynx, mouth, pharynx, larynx, neck, ears (for hearing acuity for conversational speech), and third through twelfth cranial nerves was normal, and there was no spontaneous nystagmus. A culture of the left external ear canal grew a moderate amount of coagulase-negative staphylococcus species. Topical nystatin–triamcinolone ointment was administered to the left ear twice daily for 2 weeks, without improvement.

One week later, the patient returned to the outpatient clinic. She reported near constant pruritus and bleeding that had increased in amount and frequency. The lesion in the left ear canal appeared to be unchanged from the previous examination. A small crust covered the most medial aspect of the lesion.

Nine days later, a diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient presents with a pruritic lesion in the left ear canal that has been associated with recurrent bleeding. The lesion has a cobblestone appearance and several prominent vessels. The lesion did not respond to topical or oral antibiotics, suggesting that it is not an infection. The lesion also did not respond to topical steroids, suggesting that it is not an inflammatory condition. The lesion's cobblestone appearance and resistance to treatment suggest a neoplastic process. The patient's age and the location of the lesion suggest a benign neoplasm. The most common benign neoplasm in this location is a ceruminous adenoma.\n\nDiagnosis: Ceruminous adenoma.""
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        ""content"": ""The patient presents with a pruritic lesion in the left ear canal that has been causing recurrent bleeding. The lesion has a cobblestone appearance and several prominent vessels. The lesion did not respond to topical or oral antibiotics, suggesting that it is not an infection. The lesion also did not respond to topical steroids, suggesting that it is not an inflammatory condition. The lesion's cobblestone appearance and prominent vessels suggest a vascular origin. The patient's symptoms of pruritus and bleeding are consistent with a vascular lesion. The lesion's location in the ear canal is consistent with a glomus tympanicum tumor, which is a benign vascular tumor that commonly occurs in the middle ear.\n\nDiagnosis: Glomus Tympanicum Tumor.""
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        ""content"": ""The patient is a 27-year-old woman presenting with a pruritic lesion in the left ear canal that has been causing recurrent bleeding for a year. The lesion is described as light pink, raised, with a cobblestone appearance and several prominent vessels. The differential diagnosis for this patient includes cholesteatoma, squamous cell carcinoma, basal cell carcinoma, and keratosis obturans. Cholesteatoma is less likely because the patient does not report any hearing loss or discharge, which are common symptoms of this condition. Squamous cell carcinoma and basal cell carcinoma are possibilities, but these are more common in older patients and those with significant sun exposure, neither of which apply to this patient. Keratosis obturans is a possibility, but this condition typically presents with severe pain and hearing loss, which this patient does not report. Given the patient's age, the location and appearance of the lesion, and the symptoms of pruritus and bleeding, the most likely diagnosis is a benign skin lesion such as a seborrheic keratosis or a benign vascular lesion such as a pyogenic granuloma. \n\nDiagnosis: Pyogenic granuloma.""
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}",Pyogenic granuloma,Y
10.1056/NEJMcpc1505527,Case 35-2015 — A 72-Year-Old Woman with Proteinuria and a Kidney Mass,,"PLA2R-type membranous nephropathy.

Clear-cell renal-cell carcinoma.","Renal-cell carcinoma.

Membranous glomerular disease and possible early diabetic glomerulosclerosis.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 72-year-old woman was evaluated at this hospital because of a new kidney mass.

Approximately 1.5 years before the current evaluation, while the patient was in the Dominican Republic, she sought medical attention for episodic pain of the right flank, with no other symptoms. At that time, she was told she had microscopic hematuria that may be due to kidney stones, and she received a prescription for unknown oral medications. After she took the medications, the flank pain resolved, and she had no further follow-up. Two weeks before the current evaluation, bilateral back and flank pain developed. She was evaluated at a local health center. An abdominal ultrasound examination revealed a partially exophytic mass (2.8 cm by 2.6 cm by 2.5 cm) in the lower pole of the right kidney, with mixed echogenicity and internal vascularity. No hydronephrosis or renal stones were visualized, and the sizes of the kidneys were normal. The patient was referred for a consultation with a nephrologist at this hospital.

On evaluation in the nephrology clinic of this hospital, the patient reported mild headache, nausea, and constipation; there was no abdominal or pelvic pain, hematuria, foamy urine, weight loss, anorexia, peripheral or facial edema, or rash. She had a history of stage 4 chronic kidney disease (with a baseline creatinine level of 1.8 mg per deciliter [159.1 _mol per liter]), diabetes mellitus type 2, systemic hypertension, hyperlipidemia, osteoarthritis, tinnitus, and bilateral sensorineural hearing loss and had undergone an appendectomy and a hysterectomy. Medications included aspirin, atorvastatin, atenolol, chlorthalidone, sitagliptin, and iron sulfate. The patient was from the Dominican Republic and had immigrated to the United States 1 year earlier. She had four children and was retired. She smoked two to five cigarettes daily and had done so for the past 30 years. She did not drink alcohol or use illicit drugs. She had no family history of kidney stones, renal disease, or cancer.

On examination, the patient appeared to be comfortable. The temperature was 36.5°C, the pulse 60 beats per minute, the blood pressure 154/71 mm Hg, and the oxygen saturation 98% while she was breathing ambient air. There were well-healed incisions in the right lower quadrant and along the midline of the abdomen. The abdomen was soft and nontender, without palpable masses. No flank or costovertebral-angle tenderness, inguinal lymphadenopathy, or peripheral edema was present. The remainder of the examination was normal.

Table 1.

Laboratory Data.
A complete blood count and iron studies (including levels of iron, iron-binding capacity, and ferritin) were normal, as were blood levels of electrolytes, calcium, phosphorus, and albumin; other test results are shown in Table 1. Urinalysis revealed clear, yellow urine, with a specific gravity of 1.008, a pH of 7.0, 1+ occult blood, 3+ albumin, 5 to 10 red cells and 0 to 2 white cells per high-power field, and no glucose, bilirubin, ketones, or nitrite.

A test for antinuclear antibodies was positive (at a dilution of 1:160). Tests for antibodies to double-stranded DNA, hepatitis C antibodies, hepatitis B core IgM antibodies, and Bence Jones protein were negative. Levels of C3, C4, and immunoglobulins were normal, as were the results of serum protein electrophoresis. Lisinopril was prescribed.

Figure 1.

MRI Scans.
Dr. Aoife Kilcoyne: Magnetic resonance imaging (MRI) of the kidneys was performed without the intravenous administration of gadolinium because of impaired renal function. The images showed a complex, solid mass (measuring 3.0 cm by 2.9 cm by 2.9 cm) in the lower pole of the right kidney. On T1-weighted and T2-weighted images (Figure 1A and 1B), the lesion had heterogeneous signal intensity. On T1-weighted gradient-echo in-phase and out-of-phase images (Figure 1C and 1D), there was loss of signal at the posterior aspect of the lesion, a finding consistent with the presence of intravoxel fat. The mass was suspicious for renal carcinoma.

Dr. Eneanya: Diagnostic tests were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 72-year-old woman was evaluated at this hospital because of a new kidney mass.

Approximately 1.5 years before the current evaluation, while the patient was in the Dominican Republic, she sought medical attention for episodic pain of the right flank, with no other symptoms. At that time, she was told she had microscopic hematuria that may be due to kidney stones, and she received a prescription for unknown oral medications. After she took the medications, the flank pain resolved, and she had no further follow-up. Two weeks before the current evaluation, bilateral back and flank pain developed. She was evaluated at a local health center. An abdominal ultrasound examination revealed a partially exophytic mass (2.8 cm by 2.6 cm by 2.5 cm) in the lower pole of the right kidney, with mixed echogenicity and internal vascularity. No hydronephrosis or renal stones were visualized, and the sizes of the kidneys were normal. The patient was referred for a consultation with a nephrologist at this hospital.

On evaluation in the nephrology clinic of this hospital, the patient reported mild headache, nausea, and constipation; there was no abdominal or pelvic pain, hematuria, foamy urine, weight loss, anorexia, peripheral or facial edema, or rash. She had a history of stage 4 chronic kidney disease (with a baseline creatinine level of 1.8 mg per deciliter [159.1 _mol per liter]), diabetes mellitus type 2, systemic hypertension, hyperlipidemia, osteoarthritis, tinnitus, and bilateral sensorineural hearing loss and had undergone an appendectomy and a hysterectomy. Medications included aspirin, atorvastatin, atenolol, chlorthalidone, sitagliptin, and iron sulfate. The patient was from the Dominican Republic and had immigrated to the United States 1 year earlier. She had four children and was retired. She smoked two to five cigarettes daily and had done so for the past 30 years. She did not drink alcohol or use illicit drugs. She had no family history of kidney stones, renal disease, or cancer.

On examination, the patient appeared to be comfortable. The temperature was 36.5°C, the pulse 60 beats per minute, the blood pressure 154/71 mm Hg, and the oxygen saturation 98% while she was breathing ambient air. There were well-healed incisions in the right lower quadrant and along the midline of the abdomen. The abdomen was soft and nontender, without palpable masses. No flank or costovertebral-angle tenderness, inguinal lymphadenopathy, or peripheral edema was present. The remainder of the examination was normal.

Table 1.

Laboratory Data.
A complete blood count and iron studies (including levels of iron, iron-binding capacity, and ferritin) were normal, as were blood levels of electrolytes, calcium, phosphorus, and albumin; other test results are shown in Table 1. Urinalysis revealed clear, yellow urine, with a specific gravity of 1.008, a pH of 7.0, 1+ occult blood, 3+ albumin, 5 to 10 red cells and 0 to 2 white cells per high-power field, and no glucose, bilirubin, ketones, or nitrite.

A test for antinuclear antibodies was positive (at a dilution of 1:160). Tests for antibodies to double-stranded DNA, hepatitis C antibodies, hepatitis B core IgM antibodies, and Bence Jones protein were negative. Levels of C3, C4, and immunoglobulins were normal, as were the results of serum protein electrophoresis. Lisinopril was prescribed.

Figure 1.

MRI Scans.
Dr. Aoife Kilcoyne: Magnetic resonance imaging (MRI) of the kidneys was performed without the intravenous administration of gadolinium because of impaired renal function. The images showed a complex, solid mass (measuring 3.0 cm by 2.9 cm by 2.9 cm) in the lower pole of the right kidney. On T1-weighted and T2-weighted images (Figure 1A and 1B), the lesion had heterogeneous signal intensity. On T1-weighted gradient-echo in-phase and out-of-phase images (Figure 1C and 1D), there was loss of signal at the posterior aspect of the lesion, a finding consistent with the presence of intravoxel fat. The mass was suspicious for renal carcinoma.

Dr. Eneanya: Diagnostic tests were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Renal Cell Carcinoma. The patient's symptoms of flank pain and the presence of a complex, solid mass in the lower pole of the right kidney as seen on the MRI are indicative of renal carcinoma. The loss of signal at the posterior aspect of the lesion, consistent with the presence of intravoxel fat, further supports this diagnosis.""
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        ""content"": ""The patient is a 72-year-old woman with a history of stage 4 chronic kidney disease, diabetes mellitus type 2, systemic hypertension, hyperlipidemia, osteoarthritis, tinnitus, and bilateral sensorineural hearing loss. She presented with a new kidney mass, mild headache, nausea, and constipation. The MRI showed a complex, solid mass in the lower pole of the right kidney with heterogeneous signal intensity and loss of signal at the posterior aspect of the lesion, a finding consistent with the presence of intravoxel fat. The mass was suspicious for renal carcinoma. Given the patient's age, history of smoking, and the imaging findings, the most likely diagnosis is renal cell carcinoma.""
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        ""content"": ""The patient is a 72-year-old woman with a history of chronic kidney disease, diabetes, and hypertension who presents with a new kidney mass. The differential diagnosis for a kidney mass includes renal cell carcinoma, oncocytoma, angiomyolipoma, and renal abscess. The patient's history of smoking increases her risk for renal cell carcinoma. The patient's symptoms of flank pain and microscopic hematuria are also consistent with renal cell carcinoma. The MRI findings of a complex, solid mass with heterogeneous signal intensity and loss of signal at the posterior aspect of the lesion are also suggestive of renal cell carcinoma. The absence of fever and leukocytosis makes a renal abscess less likely. Oncocytoma and angiomyolipoma are benign kidney tumors, but they are less likely given the patient's symptoms and MRI findings. \n\nDiagnosis: Renal cell carcinoma.""
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10.1056/NEJMcpc1502151,"Case 34-2015 — A 36-Year-Old Woman with a Lung Mass, Pleural Effusion, and Hip Pain",,IgG4-related pulmonary disease.,IgG4-related lung disease.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 36-year-old woman was admitted to this hospital because of a mass in the middle lobe of the right lung.

The patient had been in her usual health until 1 month before this admission, when pain in the right shoulder and discomfort in the left lower abdomen developed. The shoulder pain worsened with inspiration and was associated with nonproductive cough, intermittent fevers (to a temperature of 38.1°C), sinus pain, nasal discharge, periorbital erythema, and difficulty breathing. Eleven days before this admission, she presented to another health center for evaluation. Physical examination reportedly revealed a new cardiac murmur. A chest radiograph showed a mass in the right middle lobe and a right pleural effusion.

Table 1.

Pleural-Fluid Analysis.
Six days before this admission, an axial computed tomographic (CT) scan of the chest that was obtained at another hospital showed a homogeneous opacity (5.8 cm by 4.9 cm) extending from the pleura to the hilum, as well as interlobular septal thickening in the right middle lobe, mediastinal and right hilar lymphadenopathy, and a loculated right pleural effusion. The patient was admitted to that hospital, and thoracentesis was performed. Results of analysis of the serosanguineous pleural fluid (120-ml sample) are shown in Table 1. Culture of the fluid grew Staphylococcus lugdunensis. The patient was discharged home the next morning, with a prescription for a 5-day course of azithromycin and cefpodoxime. She was referred to the thoracic surgery service at this hospital for further evaluation and bronchoscopy.

On presentation 5 days later, bronchoscopic evaluation revealed erythema in the right bronchus intermedius and bronchus of the right middle lobe, with no endobronchial lesions or secretions. Microbiologic testing and cytologic examination of bronchoalveolar-lavage (BAL) fluid from the right middle lobe were nondiagnostic. The patient was admitted to this hospital.

The patient reported headaches and pain along the diaphragm and right shoulder on deep inspiration. At 17 years of age, she had had hydrocephalus due to a web in the aqueduct of Sylvius that resolved after temporary placement of a right frontal ventriculoperitoneal shunt and performance of an endoscopic third ventriculostomy. Temporal-lobe epilepsy later developed and was caused by a right mesial temporal cavernous malformation that was successfully resected. A second cavernous malformation in the cerebellum had been stable on serial magnetic resonance imaging (MRI). The patient was born in Europe and had moved to the United States 8 years earlier. She had visited Switzerland, California, and Michigan during the previous year, and she had visited Cuba 10 years earlier. She was married and worked in a research field, with exposures to yeast and mice 2 years earlier. She did not smoke, drink alcohol, or use illicit drugs. She had a family history of rheumatoid arthritis, coronary artery disease, hypertension, and asthma.

On examination, the temperature was 37.5°C, and the pulse 101 beats per minute; the other vital signs were normal. Decreased breath sounds in the right lung and a soft cardiac murmur were present. The examination was otherwise normal.

Figure 1.

CT Scans Obtained on the First Admission.
Dr. Subba R. Digumarthy: An axial CT scan of the chest, obtained without the administration of contrast material, showed a homogeneous opacity (5.8 cm by 4.9 cm) extending from the pleura to the hilum, as well as interlobular septal thickening in the right middle lobe, a nodule (3 mm in diameter) in the right upper lobe, atelectasis in both lower lobes, and a loculated right pleural effusion that was bigger than that seen on the scan obtained 6 days earlier (Figure 1).

Table 2.

Peripheral-Blood Laboratory Data.
Dr. Dezube: Blood levels of calcium, magnesium, and phosphorus were normal, as were results of renal-function tests; other test results are shown in Table 2. Vancomycin, cefepime, and metronidazole were administered for 1 day after the bronchoscopy.

The next day, a chest tube was inserted into the right pleural space, and 1600 ml of yellow pleural fluid was drained; results of pleural-fluid analysis are shown in Table 1. Cytologic examination of the fluid revealed mesothelial cells, histiocytes, and neutrophils but no malignant cells. On the fourth day, the chest tube was removed. The patient was discharged home the following day, with a prescription for a 3-week course of ceftriaxone.

During the next month, follow-up imaging studies of the chest showed increasing nodular thickening of the right major fissure, a left pleural effusion, and a decreasing right pleural effusion; the findings were otherwise stable. Pathological examination of specimens obtained from a percutaneous fine-needle aspiration biopsy and core biopsy of the large mass in the right middle lobe showed mixed inflammation, with lymphocytes, plasma cells, and neutrophils. Microbiologic staining and cultures for bacteria, mycobacteria, and fungi were negative.

One month after admission to this hospital, symptoms persisted and the patient was readmitted for further evaluation. She reported a dry cough, dyspnea, generalized fatigue, weakness, and pain in her shoulders, neck, and lower back. Medications included narcotic analgesic agents, ranitidine, calcium carbonate, and acetaminophen.

On examination, the vital signs were normal, and the oxygen saturation was 95% while the patient was breathing ambient air. The breath sounds were decreased bilaterally; the decrease was greater on the left side than on the right. Pulmonary-function testing revealed a forced expiratory volume in 1 second of 1.18 liters (37% of the predicted value), a forced vital capacity of 1.40 liters (36% of the predicted value), a peak expiratory flow rate of 4.25 liters per minute (65% of the predicted value), and a carbon monoxide diffusing capacity corrected for alveolar volume of 3.47 ml per minute per millimeter of mercury per liter (62% of the predicted value). Results of coagulation tests and blood levels of calcium, phosphorus, magnesium, glucose, total bilirubin, direct bilirubin, and aspartate and alanine aminotransferases were normal; other test results are shown in Table 2. Urinalysis was normal. Chest radiographs showed a mass in the right middle lobe, a patchy left basilar opacity that was consistent with atelectasis, a stable right pleural effusion, and a moderate left pleural effusion. A pigtail catheter was inserted into the left pleural space. Cytologic examination of serosanguineous pleural fluid (75-ml sample) revealed mesothelial cells, histiocytes, lymphocytes, and neutrophils; other test results are shown in Table 1.

The next day, thoracoscopy, lobectomies of the right middle and lower lobes, total pulmonary decortication, and dissection of mediastinal lymph nodes were all performed with the use of video-assisted techniques. Pathological examination revealed evidence of extensive lipoid pneumonia (i.e., the accumulation of lipids in the alveoli) and fibrinous pleuritis. The patient had no complications associated with the procedures and was discharged home 5 days later.

During the next 5 months, the patient had persistent dyspnea on exertion and pain in the inferior portion of the chest that was thought to be musculoskeletal. Chest radiographs showed postoperative changes and pleural effusions, without infiltrates. Six months after the first admission to this hospital, examination revealed crackles, for which an antibiotic agent was administered; the symptoms improved. Three weeks later, cardiopulmonary testing with the use of a modified Bruce protocol, performed at rest and after 12 minutes of exercise, revealed pulses of 96 and 151 beats per minute and oxygen saturations of 99% and 88% (while the patient was breathing ambient air), respectively.

Two weeks later, at an outpatient visit, the patient reported night sweats, persistent cough, fatigue, and sinus congestion. Laboratory test results are shown in Table 2.

Figure 2.

CT Scans Obtained 7 Months after the First Admission.
Dr. Digumarthy: A chest CT that was obtained during that visit showed new bilateral, subpleural ground-glass and reticular opacities. Subpleural nodular consolidation in the left lower lobe and consolidation in the medial right lung around the bronchial stump were present (Figure 2).

Dr. Dezube: Bronchoscopy was performed, and cytologic examination and microbiologic testing of the BAL fluid were nondiagnostic. Flow cytometry revealed 34% granulocytes, a finding consistent with inflammation. Chest pain, which the patient rated at 5 out of 10 at rest and 8 out of 10 with deep inspiration and coughing (on a scale of 0 to 10, with 10 indicating the most severe pain), persisted despite administration of amoxicillin–clavulanate, glucocorticoid therapy, and a narcotic analgesic agent.

One week later, pain in the right hip developed, without a known injury. The following week, examination revealed pain on active flexion of the right hip. Test results are shown in Table 2.

Dr. Digumarthy: MRI of the hip, performed without the administration of contrast material, revealed a right superior labral tear with a surrounding inflammatory change (2.0 cm by 1.7 cm) along the proximal right iliopsoas muscle and a left adnexal cyst (4.0 cm by 2.5 cm); there was no evidence of fracture or osteonecrosis. MRI of the pelvis was performed; T2-weighted images showed an abnormal signal that extended along the right iliac vessels and involved the adjacent medial right psoas and iliacus muscles, with no fluid collection. A hemorrhagic left ovarian cyst and a right paracentral disk protrusion at L4–L5 that had contact with the descending right L4 nerve roots were also noted.

Dr. Dezube: A diagnosis was made.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 36-year-old woman was admitted to this hospital because of a mass in the middle lobe of the right lung.

The patient had been in her usual health until 1 month before this admission, when pain in the right shoulder and discomfort in the left lower abdomen developed. The shoulder pain worsened with inspiration and was associated with nonproductive cough, intermittent fevers (to a temperature of 38.1°C), sinus pain, nasal discharge, periorbital erythema, and difficulty breathing. Eleven days before this admission, she presented to another health center for evaluation. Physical examination reportedly revealed a new cardiac murmur. A chest radiograph showed a mass in the right middle lobe and a right pleural effusion.

Table 1.

Pleural-Fluid Analysis.
Six days before this admission, an axial computed tomographic (CT) scan of the chest that was obtained at another hospital showed a homogeneous opacity (5.8 cm by 4.9 cm) extending from the pleura to the hilum, as well as interlobular septal thickening in the right middle lobe, mediastinal and right hilar lymphadenopathy, and a loculated right pleural effusion. The patient was admitted to that hospital, and thoracentesis was performed. Results of analysis of the serosanguineous pleural fluid (120-ml sample) are shown in Table 1. Culture of the fluid grew Staphylococcus lugdunensis. The patient was discharged home the next morning, with a prescription for a 5-day course of azithromycin and cefpodoxime. She was referred to the thoracic surgery service at this hospital for further evaluation and bronchoscopy.

On presentation 5 days later, bronchoscopic evaluation revealed erythema in the right bronchus intermedius and bronchus of the right middle lobe, with no endobronchial lesions or secretions. Microbiologic testing and cytologic examination of bronchoalveolar-lavage (BAL) fluid from the right middle lobe were nondiagnostic. The patient was admitted to this hospital.

The patient reported headaches and pain along the diaphragm and right shoulder on deep inspiration. At 17 years of age, she had had hydrocephalus due to a web in the aqueduct of Sylvius that resolved after temporary placement of a right frontal ventriculoperitoneal shunt and performance of an endoscopic third ventriculostomy. Temporal-lobe epilepsy later developed and was caused by a right mesial temporal cavernous malformation that was successfully resected. A second cavernous malformation in the cerebellum had been stable on serial magnetic resonance imaging (MRI). The patient was born in Europe and had moved to the United States 8 years earlier. She had visited Switzerland, California, and Michigan during the previous year, and she had visited Cuba 10 years earlier. She was married and worked in a research field, with exposures to yeast and mice 2 years earlier. She did not smoke, drink alcohol, or use illicit drugs. She had a family history of rheumatoid arthritis, coronary artery disease, hypertension, and asthma.

On examination, the temperature was 37.5°C, and the pulse 101 beats per minute; the other vital signs were normal. Decreased breath sounds in the right lung and a soft cardiac murmur were present. The examination was otherwise normal.

Figure 1.

CT Scans Obtained on the First Admission.
Dr. Subba R. Digumarthy: An axial CT scan of the chest, obtained without the administration of contrast material, showed a homogeneous opacity (5.8 cm by 4.9 cm) extending from the pleura to the hilum, as well as interlobular septal thickening in the right middle lobe, a nodule (3 mm in diameter) in the right upper lobe, atelectasis in both lower lobes, and a loculated right pleural effusion that was bigger than that seen on the scan obtained 6 days earlier (Figure 1).

Table 2.

Peripheral-Blood Laboratory Data.
Dr. Dezube: Blood levels of calcium, magnesium, and phosphorus were normal, as were results of renal-function tests; other test results are shown in Table 2. Vancomycin, cefepime, and metronidazole were administered for 1 day after the bronchoscopy.

The next day, a chest tube was inserted into the right pleural space, and 1600 ml of yellow pleural fluid was drained; results of pleural-fluid analysis are shown in Table 1. Cytologic examination of the fluid revealed mesothelial cells, histiocytes, and neutrophils but no malignant cells. On the fourth day, the chest tube was removed. The patient was discharged home the following day, with a prescription for a 3-week course of ceftriaxone.

During the next month, follow-up imaging studies of the chest showed increasing nodular thickening of the right major fissure, a left pleural effusion, and a decreasing right pleural effusion; the findings were otherwise stable. Pathological examination of specimens obtained from a percutaneous fine-needle aspiration biopsy and core biopsy of the large mass in the right middle lobe showed mixed inflammation, with lymphocytes, plasma cells, and neutrophils. Microbiologic staining and cultures for bacteria, mycobacteria, and fungi were negative.

One month after admission to this hospital, symptoms persisted and the patient was readmitted for further evaluation. She reported a dry cough, dyspnea, generalized fatigue, weakness, and pain in her shoulders, neck, and lower back. Medications included narcotic analgesic agents, ranitidine, calcium carbonate, and acetaminophen.

On examination, the vital signs were normal, and the oxygen saturation was 95% while the patient was breathing ambient air. The breath sounds were decreased bilaterally; the decrease was greater on the left side than on the right. Pulmonary-function testing revealed a forced expiratory volume in 1 second of 1.18 liters (37% of the predicted value), a forced vital capacity of 1.40 liters (36% of the predicted value), a peak expiratory flow rate of 4.25 liters per minute (65% of the predicted value), and a carbon monoxide diffusing capacity corrected for alveolar volume of 3.47 ml per minute per millimeter of mercury per liter (62% of the predicted value). Results of coagulation tests and blood levels of calcium, phosphorus, magnesium, glucose, total bilirubin, direct bilirubin, and aspartate and alanine aminotransferases were normal; other test results are shown in Table 2. Urinalysis was normal. Chest radiographs showed a mass in the right middle lobe, a patchy left basilar opacity that was consistent with atelectasis, a stable right pleural effusion, and a moderate left pleural effusion. A pigtail catheter was inserted into the left pleural space. Cytologic examination of serosanguineous pleural fluid (75-ml sample) revealed mesothelial cells, histiocytes, lymphocytes, and neutrophils; other test results are shown in Table 1.

The next day, thoracoscopy, lobectomies of the right middle and lower lobes, total pulmonary decortication, and dissection of mediastinal lymph nodes were all performed with the use of video-assisted techniques. Pathological examination revealed evidence of extensive lipoid pneumonia (i.e., the accumulation of lipids in the alveoli) and fibrinous pleuritis. The patient had no complications associated with the procedures and was discharged home 5 days later.

During the next 5 months, the patient had persistent dyspnea on exertion and pain in the inferior portion of the chest that was thought to be musculoskeletal. Chest radiographs showed postoperative changes and pleural effusions, without infiltrates. Six months after the first admission to this hospital, examination revealed crackles, for which an antibiotic agent was administered; the symptoms improved. Three weeks later, cardiopulmonary testing with the use of a modified Bruce protocol, performed at rest and after 12 minutes of exercise, revealed pulses of 96 and 151 beats per minute and oxygen saturations of 99% and 88% (while the patient was breathing ambient air), respectively.

Two weeks later, at an outpatient visit, the patient reported night sweats, persistent cough, fatigue, and sinus congestion. Laboratory test results are shown in Table 2.

Figure 2.

CT Scans Obtained 7 Months after the First Admission.
Dr. Digumarthy: A chest CT that was obtained during that visit showed new bilateral, subpleural ground-glass and reticular opacities. Subpleural nodular consolidation in the left lower lobe and consolidation in the medial right lung around the bronchial stump were present (Figure 2).

Dr. Dezube: Bronchoscopy was performed, and cytologic examination and microbiologic testing of the BAL fluid were nondiagnostic. Flow cytometry revealed 34% granulocytes, a finding consistent with inflammation. Chest pain, which the patient rated at 5 out of 10 at rest and 8 out of 10 with deep inspiration and coughing (on a scale of 0 to 10, with 10 indicating the most severe pain), persisted despite administration of amoxicillin–clavulanate, glucocorticoid therapy, and a narcotic analgesic agent.

One week later, pain in the right hip developed, without a known injury. The following week, examination revealed pain on active flexion of the right hip. Test results are shown in Table 2.

Dr. Digumarthy: MRI of the hip, performed without the administration of contrast material, revealed a right superior labral tear with a surrounding inflammatory change (2.0 cm by 1.7 cm) along the proximal right iliopsoas muscle and a left adnexal cyst (4.0 cm by 2.5 cm); there was no evidence of fracture or osteonecrosis. MRI of the pelvis was performed; T2-weighted images showed an abnormal signal that extended along the right iliac vessels and involved the adjacent medial right psoas and iliacus muscles, with no fluid collection. A hemorrhagic left ovarian cyst and a right paracentral disk protrusion at L4–L5 that had contact with the descending right L4 nerve roots were also noted.

Dr. Dezube: A diagnosis was made.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""Exogenous lipoid pneumonia\n\nThe patient presented with a mass in the right middle lobe of the lung, shoulder pain, cough, fevers, and difficulty breathing. Imaging revealed a homogeneous opacity in the right middle lobe, interlobular septal thickening, mediastinal and right hilar lymphadenopathy, and a loculated right pleural effusion. Pleural fluid analysis showed lymphocytes, plasma cells, and neutrophils, but no malignant cells. Despite antibiotic treatment, the patient's symptoms persisted and further imaging showed increasing nodular thickening of the right major fissure, a left pleural effusion, and a decreasing right pleural effusion. Pathological examination of specimens obtained from a percutaneous fine-needle aspiration biopsy and core biopsy of the large mass in the right middle lobe showed mixed inflammation. The patient was readmitted to the hospital a month later with persistent symptoms. Thoracoscopy, lobectomies of the right middle and lower lobes, total pulmonary decortication, and dissection of mediastinal lymph nodes were performed. Pathological examination revealed evidence of extensive lipoid pneumonia and fibrinous pleuritis. Lipoid pneumonia is a rare condition that occurs when fat particles enter the lungs. It can be caused by aspiration of oils or associated with lipid-laden macrophages. The patient's persistent symptoms, the presence of a lung mass, and the pathological findings of lipoid pneumonia all point to a diagnosis of exogenous lipoid pneumonia.""
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        ""content"": ""Exogenous Lipoid Pneumonia\n\nThe patient presented with a mass in the right middle lobe of the lung, shoulder pain, cough, fevers, and difficulty breathing. Imaging revealed a homogeneous opacity in the right middle lobe, interlobular septal thickening, mediastinal and right hilar lymphadenopathy, and a loculated right pleural effusion. Pleural fluid analysis showed lymphocytes, plasma cells, and neutrophils, but no malignant cells. Despite antibiotic treatment, the patient's symptoms persisted and further imaging showed increasing nodular thickening of the right major fissure, a left pleural effusion, and a decreasing right pleural effusion. Pathological examination of specimens obtained from a percutaneous fine-needle aspiration biopsy and core biopsy of the large mass in the right middle lobe showed mixed inflammation. The patient underwent thoracoscopy, lobectomies of the right middle and lower lobes, total pulmonary decortication, and dissection of mediastinal lymph nodes. Pathological examination revealed evidence of extensive lipoid pneumonia (i.e., the accumulation of lipids in the alveoli) and fibrinous pleuritis. The patient's persistent symptoms and the findings of lipids in the alveoli suggest a diagnosis of exogenous lipoid pneumonia, a rare condition caused by the inhalation or aspiration of fat-containing substances.""
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        ""content"": ""Exogenous lipoid pneumonia\n\nThis patient presents with a lung mass, shoulder pain, cough, fever, and difficulty breathing. The differential diagnosis includes lung cancer, pneumonia, tuberculosis, and fungal infection. The patient's history of exposure to yeast and mice could suggest a fungal infection, but the lack of response to antibiotics and the negative cultures make this less likely. The patient's history of epilepsy and hydrocephalus is not likely related to her current symptoms. The CT scan shows a homogeneous opacity in the right middle lobe, interlobular septal thickening, mediastinal and right hilar lymphadenopathy, and a loculated right pleural effusion. These findings could be consistent with a lung tumor, but the patient's young age and lack of smoking history make lung cancer less likely. The presence of Staphylococcus lugdunensis in the pleural fluid could suggest a bacterial infection, but the lack of response to antibiotics makes this less likely. The pathological examination of the lung mass shows mixed inflammation, which is not typical of lung cancer. The final clue is the presence of lipoid pneumonia on pathological examination. This condition is caused by the inhalation or aspiration of lipids, and can present with a lung mass and symptoms of pneumonia. The patient's history does not reveal a clear source of lipid exposure, but this diagnosis is the best fit for her clinical presentation and test results.""
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 10.1056/NEJMcpc1413304,Case 33-2015 — A 57-Year-Old Woman with Hair Loss and Deepening Voice,,Ovarian hyperthecosis.,Ovarian hyperthecosis.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 57-year-old woman was seen in the outpatient gynecology clinic of this hospital because of hirsutism, hair loss on the scalp, and deepening of her voice.

One month before this presentation, the patient was seen at the outpatient gynecology clinic of another hospital. She reported a 3-year history of hair growth on her face, as well as a 1-year history of prominent symptoms, including increased hair growth on her abdomen, hair loss primarily on the top of her head, deepening of her voice, growth of skin tags on her neck and breast, and an increased libido. Laboratory testing revealed elevated total and free testosterone levels and a normal dehydroepiandrosterone sulfate (DHEAS) level. A Papanicolaou test was negative for intraepithelial lesions and cancer, and testing for high-risk human papillomavirus was negative.

Table 1.

Laboratory Data.
Twenty-one days before this presentation, the patient was seen at a second hospital by an endocrinologist, who completed an evaluation and ordered a comprehensive panel of laboratory tests to evaluate her hyperandrogenism. Laboratory test results are shown in Table 1. Five days later, a 24-hour urine collection contained 6.0 _g of cortisol (reference range, 3.5 to 45.0) in a 1050-ml sample. One week later, computed tomography (CT) of the abdomen was performed and revealed diffuse fatty infiltration of the liver without focal hepatic lesions, a nonobstructing stone (3 mm in diameter, with a density of approximately 300 Hounsfield units) in the interpolar region of the right kidney, surgical clips in the gallbladder fossa that were consistent with cholecystectomy, and degenerative changes in the visualized skeleton, with no splenomegaly, adrenal nodules, or lymphadenopathy. After these imaging and laboratory evaluations were performed, the patient was seen in the outpatient gynecology clinic of this hospital for further evaluation and treatment.

The patient was gravida 3, para 3, with normal pregnancies; menses had begun at 12 years of age and had occurred every 40 to 60 days thereafter until menopause, which had occurred 3 years before this presentation. Postmenopausal bleeding had recently occurred. In addition, the patient had hypothyroidism, hypertension, interstitial cystitis, gastroesophageal reflux disease, degenerative osteoarthritis (for which multiple glucocorticoid injections had been administered to the knees), carpal tunnel syndrome, vitamin D deficiency, an erythematous rash on the face, including the nasolabial folds (which had lasted for several years and, on dermatologic evaluation 2 years earlier, was not thought to be typical of systemic lupus erythematosus), and a positive antinuclear antibody test (speckled and centromere pattern, 1:160 dilution). She had had two cesarean sections, a total hip replacement, a cholecystectomy, and a tonsillectomy. Medications included levothyroxine, valsartan, hydrochlorothiazide, hydroxyzine, calcium, vitamin D, ibuprofen, biotin, and folate. She had no known allergies. She lived with her husband and had adult children. She drank alcohol occasionally and did not smoke or use illicit drugs. Her mother had died at 69 years of age and had had hypertension and breast cancer, one brother had diabetes mellitus, and another brother had hypertension and hyperlipidemia; there was no family history of gynecologic cancer.

On examination, the blood pressure was 137/86 mm Hg, the pulse 93 beats per minute, the respiratory rate 16 breaths per minute, the temperature 36.6°C, and the weight 103.2 kg. There was growth of dark brown terminal hair on the upper lip, chin, submental region, and neck and hair loss on the frontal region and vertex of the scalp. A pelvic examination revealed normal female external genitalia, without clitoromegaly, cervical motion tenderness, uterine pain, or adnexal pain, fullness, or masses. The remainder of the examination was normal. The white-cell count, differential count, platelet count, and red-cell indexes were normal, as were blood levels of total protein, albumin, globulin, total bilirubin, aspartate aminotransferase, and alanine aminotransferase and results of coagulation and renal-function tests; other test results are shown in Table 1. A chest radiograph showed no evidence of pneumonia or pulmonary edema.

Three weeks later, a diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 57-year-old woman was seen in the outpatient gynecology clinic of this hospital because of hirsutism, hair loss on the scalp, and deepening of her voice.

One month before this presentation, the patient was seen at the outpatient gynecology clinic of another hospital. She reported a 3-year history of hair growth on her face, as well as a 1-year history of prominent symptoms, including increased hair growth on her abdomen, hair loss primarily on the top of her head, deepening of her voice, growth of skin tags on her neck and breast, and an increased libido. Laboratory testing revealed elevated total and free testosterone levels and a normal dehydroepiandrosterone sulfate (DHEAS) level. A Papanicolaou test was negative for intraepithelial lesions and cancer, and testing for high-risk human papillomavirus was negative.

Table 1.

Laboratory Data.
Twenty-one days before this presentation, the patient was seen at a second hospital by an endocrinologist, who completed an evaluation and ordered a comprehensive panel of laboratory tests to evaluate her hyperandrogenism. Laboratory test results are shown in Table 1. Five days later, a 24-hour urine collection contained 6.0 _g of cortisol (reference range, 3.5 to 45.0) in a 1050-ml sample. One week later, computed tomography (CT) of the abdomen was performed and revealed diffuse fatty infiltration of the liver without focal hepatic lesions, a nonobstructing stone (3 mm in diameter, with a density of approximately 300 Hounsfield units) in the interpolar region of the right kidney, surgical clips in the gallbladder fossa that were consistent with cholecystectomy, and degenerative changes in the visualized skeleton, with no splenomegaly, adrenal nodules, or lymphadenopathy. After these imaging and laboratory evaluations were performed, the patient was seen in the outpatient gynecology clinic of this hospital for further evaluation and treatment.

The patient was gravida 3, para 3, with normal pregnancies; menses had begun at 12 years of age and had occurred every 40 to 60 days thereafter until menopause, which had occurred 3 years before this presentation. Postmenopausal bleeding had recently occurred. In addition, the patient had hypothyroidism, hypertension, interstitial cystitis, gastroesophageal reflux disease, degenerative osteoarthritis (for which multiple glucocorticoid injections had been administered to the knees), carpal tunnel syndrome, vitamin D deficiency, an erythematous rash on the face, including the nasolabial folds (which had lasted for several years and, on dermatologic evaluation 2 years earlier, was not thought to be typical of systemic lupus erythematosus), and a positive antinuclear antibody test (speckled and centromere pattern, 1:160 dilution). She had had two cesarean sections, a total hip replacement, a cholecystectomy, and a tonsillectomy. Medications included levothyroxine, valsartan, hydrochlorothiazide, hydroxyzine, calcium, vitamin D, ibuprofen, biotin, and folate. She had no known allergies. She lived with her husband and had adult children. She drank alcohol occasionally and did not smoke or use illicit drugs. Her mother had died at 69 years of age and had had hypertension and breast cancer, one brother had diabetes mellitus, and another brother had hypertension and hyperlipidemia; there was no family history of gynecologic cancer.

On examination, the blood pressure was 137/86 mm Hg, the pulse 93 beats per minute, the respiratory rate 16 breaths per minute, the temperature 36.6°C, and the weight 103.2 kg. There was growth of dark brown terminal hair on the upper lip, chin, submental region, and neck and hair loss on the frontal region and vertex of the scalp. A pelvic examination revealed normal female external genitalia, without clitoromegaly, cervical motion tenderness, uterine pain, or adnexal pain, fullness, or masses. The remainder of the examination was normal. The white-cell count, differential count, platelet count, and red-cell indexes were normal, as were blood levels of total protein, albumin, globulin, total bilirubin, aspartate aminotransferase, and alanine aminotransferase and results of coagulation and renal-function tests; other test results are shown in Table 1. A chest radiograph showed no evidence of pneumonia or pulmonary edema.

Three weeks later, a diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient is a postmenopausal woman presenting with hirsutism, hair loss on the scalp, and deepening of her voice. These symptoms, along with the elevated total and free testosterone levels, suggest a condition causing hyperandrogenism. The normal DHEAS level and the absence of adrenal nodules on CT scan make an adrenal source of androgen less likely. The absence of clitoromegaly on examination also makes an ovarian tumor less likely. The patient's history of menopause, recent postmenopausal bleeding, and elevated testosterone levels suggest an ovarian source of androgen, most likely an ovarian neoplasm, such as a Sertoli-Leydig cell tumor, which can secrete testosterone.\n\nDiagnosis: Ovarian neoplasm, likely a Sertoli-Leydig cell tumor.""
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        ""content"": ""The patient is a postmenopausal woman presenting with hirsutism, hair loss on the scalp, and deepening of her voice. These symptoms, along with her increased libido, suggest hyperandrogenism. Laboratory tests confirm elevated total and free testosterone levels. However, her DHEAS level is normal, which suggests that the source of the excess androgens is not the adrenal glands. CT of the abdomen did not reveal any adrenal nodules, further supporting this. The patient does not have any signs of Cushing's syndrome such as central obesity, moon face, or purple striae, which makes an adrenal tumor unlikely. The patient's symptoms started after menopause, which suggests an ovarian source for the excess androgens. The most common ovarian source of androgens in postmenopausal women is an ovarian tumor. \n\nDiagnosis: Ovarian tumor causing hyperandrogenism.""
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        ""content"": ""The patient is a 57-year-old woman presenting with hirsutism, hair loss on the scalp, and deepening of her voice. These symptoms, along with her elevated total and free testosterone levels, suggest a condition causing hyperandrogenism. The differential diagnosis includes polycystic ovary syndrome (PCOS), adrenal tumors, ovarian tumors, and Cushing's syndrome. However, the patient is postmenopausal, which makes PCOS less likely. Additionally, her CT scan did not reveal any adrenal nodules or lymphadenopathy, making adrenal tumors unlikely. Her normal DHEAS level also makes adrenal causes less likely. Cushing's syndrome is also less likely given her normal 24-hour urine cortisol level. The patient's symptoms and lab findings are most consistent with an ovarian source of androgen production, such as an ovarian tumor. \n\nDiagnosis: Ovarian tumor causing hyperandrogenism.""
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10.1056/NEJMcpc1503830,Case 32-2015 — A 57-Year-Old Man with Severe Pneumonia and Hypoxemic Respiratory Failure,,"Disseminated pulmonary blastomycosis involving the hilar lymph nodes and spleen, early hepatic cirrhosis, and acute tubular necrosis.","Severe pulmonary blastomycosis, with the acute respiratory distress syndrome and probable dissemination.","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 57-year-old man was admitted to the medical intensive care unit (ICU) of this hospital in the winter because of severe pneumonia and acute hypoxemic respiratory failure.

The patient had been well until 21 days before this admission, when myalgias, arthralgias, chills, fever (with a temperature of 39.2°C), and upper respiratory symptoms occurred. Seven days later, he was seen by his physician because of worsening symptoms. A rapid test for influenza virus was reportedly negative. A diagnosis of possible influenza was made, and supportive care was advised. The next day, he was seen in the emergency department of another hospital. A chest radiograph reportedly showed evidence of pneumonia in the left upper lobe. Ceftriaxone and azithromycin were administered intravenously, azithromycin and an albuterol inhaler were prescribed, and the patient was discharged home.

Table 1.

Laboratory Data.
Two days later, 11 days before this admission, the patient called his physician because of persistent symptoms; prednisone and cough syrup were prescribed. After 2 more days, he was seen by an infectious-disease specialist in the outpatient clinic of another hospital. He reported exhaustion, fever (with a temperature of 38.9°C) despite having taken acetaminophen, and cough with blood-tinged sputum and pleuritic chest pain that prevented him from sleeping. On examination, he had dyspnea. The blood pressure was 148/71 mm Hg, the pulse between 88 and 120 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 94% while he was breathing ambient air at rest. There were crackles at the left lung base and left axillary region. Laboratory test results are shown in Table 1. A chest radiograph revealed a dense infiltrate on the left side. A diagnosis of severe community-acquired pneumonia was made, and the patient was admitted to the other hospital. Ceftriaxone and moxifloxacin were administered.

Figure 1.

Chest Radiographs.
Dr. Jeanne B. Ackman: Posteroanterior and lateral chest radiographs that were obtained 6 days before this admission (Figure 1A and 1B) showed severe consolidation in the left upper lobe, relatively mild consolidation in the right upper lobe, a trace left pleural effusion, and no obvious lymphadenopathy. Subsequent portable anteroposterior chest radiographs that were obtained during the next 5 days (Figure 1C) revealed further opacification of the left lung, with predominant involvement of the upper lobe, and worsening multifocal consolidation in the right lung that was most severe in the right upper lobe.

Dr. Hundemer: Vancomycin therapy was initiated on the third day at the other hospital, and imipenem therapy was initiated on the fifth day. On the sixth day (4 days before admission to this hospital), hypoxemia occurred, and an increasing amount of supplemental oxygen was required. The level of _1-antitrypsin was 270 mg per deciliter (reference range, 93 to 209). The anion gap and blood levels of alanine aminotransferase, total bilirubin, IgG, and IgM were normal; other test results are shown in Table 1. The patient was transferred to the medical ICU. Bronchoscopic examination revealed purulent secretions, without mucous plugs or masses. Cultures of sputum specimens were negative. Echocardiography revealed normal biventricular function and wall motion, and the left ventricular ejection fraction was 60 to 65%. On the ninth day at the other hospital, bilevel positive airway pressure was administered, with some improvement. Later that day, the trachea was electively intubated and methylprednisolone was administered. Cultures of the sputum grew candida species; blood cultures were negative.

On the 10th day at the other hospital, the patient was transferred by helicopter to this hospital (according to his family’s wishes) and admitted to the medical ICU. Medications at the time of transfer were fentanyl, midazolam, and norepinephrine by intravenous infusions, as well as vecuronium, imipenem, moxifloxacin, vancomycin, pantoprazole, ondansetron, methylprednisolone, sodium succinate, acetaminophen, enoxaparin, albuterol by nebulizer, fluticasone nasal spray, and nystatin suspension.

The patient had gout, for which he took indomethacin as needed. He had received an influenza vaccination earlier that season. He had no known allergies. He was married, had adult children, and lived in a semirural area of New England. He worked in manufacturing and had traveled for work to Indonesia and Japan during the month before this admission and to northern New England and the region surrounding the St. Lawrence River basin frequently during the previous year. His coworkers had not been ill. He reportedly did not participate in outdoor sports activities. He had a history of 40 pack-years of smoking and had stopped smoking 6 months before this admission; he drank alcohol infrequently and did not use illicit drugs. His mother and sister had _1-antitrypsin deficiency, his mother had chronic obstructive pulmonary disease, and his father had died at 63 years of age from myocardial infarction.

On examination, the patient was intubated, sedated, and afebrile. The blood pressure was 89/22 mm Hg, the pulse 50 beats per minute, and the respiratory rate 28 breaths per minute while he was receiving ventilatory support. There were coarse breath sounds bilaterally and diffuse 2+ edema of the arms and legs; the heart sounds and abdomen were normal. The plasma anion gap and results of serum protein electrophoresis were normal, as were blood levels of alanine aminotransferase, total and direct bilirubin, globulin, amylase, lipase, IgG, IgM, C3, and C4; other test results are shown in Table 1. Urinalysis revealed cloudy, yellow urine, with 1+ albumin and 2+ urobilinogen by dipstick. There were 5 to 10 red cells, 3 to 5 white cells, a few squamous cells, very few transitional cells, and very few renal tubular cells per high-power field, 20 to 100 hyaline casts and 20 to 100 granular casts per low-power field, and mucin.

Dr. Ackman: A chest radiograph that was obtained at the time of admission to this hospital revealed placement of endotracheal and esophagogastric tubes. There was a further increase in severe bilateral multifocal consolidation, without pneumothorax or definite pleural effusion (Figure 1D).

Dr. Hundemer: The fraction of inspired oxygen (Fio2) was increased to 1.00, and the partial pressure of arterial oxygen (Pao2) rose to 93 mm Hg, with an oxygen saturation of 95%. Methylprednisolone, meropenem, and continuous infusions of fentanyl, vasopressin, and propofol were administered; imipenem was discontinued. Gram’s staining of a sputum specimen revealed a moderate amount of polymorphonuclear leukocytes and no organisms; testing for antigens to adenovirus, parainfluenza, and respiratory syncytial virus was negative, as was nucleic acid testing for influenza A and B viruses.

Diagnostic procedures were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 57-year-old man was admitted to the medical intensive care unit (ICU) of this hospital in the winter because of severe pneumonia and acute hypoxemic respiratory failure.

The patient had been well until 21 days before this admission, when myalgias, arthralgias, chills, fever (with a temperature of 39.2°C), and upper respiratory symptoms occurred. Seven days later, he was seen by his physician because of worsening symptoms. A rapid test for influenza virus was reportedly negative. A diagnosis of possible influenza was made, and supportive care was advised. The next day, he was seen in the emergency department of another hospital. A chest radiograph reportedly showed evidence of pneumonia in the left upper lobe. Ceftriaxone and azithromycin were administered intravenously, azithromycin and an albuterol inhaler were prescribed, and the patient was discharged home.

Table 1.

Laboratory Data.
Two days later, 11 days before this admission, the patient called his physician because of persistent symptoms; prednisone and cough syrup were prescribed. After 2 more days, he was seen by an infectious-disease specialist in the outpatient clinic of another hospital. He reported exhaustion, fever (with a temperature of 38.9°C) despite having taken acetaminophen, and cough with blood-tinged sputum and pleuritic chest pain that prevented him from sleeping. On examination, he had dyspnea. The blood pressure was 148/71 mm Hg, the pulse between 88 and 120 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 94% while he was breathing ambient air at rest. There were crackles at the left lung base and left axillary region. Laboratory test results are shown in Table 1. A chest radiograph revealed a dense infiltrate on the left side. A diagnosis of severe community-acquired pneumonia was made, and the patient was admitted to the other hospital. Ceftriaxone and moxifloxacin were administered.

Figure 1.

Chest Radiographs.
Dr. Jeanne B. Ackman: Posteroanterior and lateral chest radiographs that were obtained 6 days before this admission (Figure 1A and 1B) showed severe consolidation in the left upper lobe, relatively mild consolidation in the right upper lobe, a trace left pleural effusion, and no obvious lymphadenopathy. Subsequent portable anteroposterior chest radiographs that were obtained during the next 5 days (Figure 1C) revealed further opacification of the left lung, with predominant involvement of the upper lobe, and worsening multifocal consolidation in the right lung that was most severe in the right upper lobe.

Dr. Hundemer: Vancomycin therapy was initiated on the third day at the other hospital, and imipenem therapy was initiated on the fifth day. On the sixth day (4 days before admission to this hospital), hypoxemia occurred, and an increasing amount of supplemental oxygen was required. The level of _1-antitrypsin was 270 mg per deciliter (reference range, 93 to 209). The anion gap and blood levels of alanine aminotransferase, total bilirubin, IgG, and IgM were normal; other test results are shown in Table 1. The patient was transferred to the medical ICU. Bronchoscopic examination revealed purulent secretions, without mucous plugs or masses. Cultures of sputum specimens were negative. Echocardiography revealed normal biventricular function and wall motion, and the left ventricular ejection fraction was 60 to 65%. On the ninth day at the other hospital, bilevel positive airway pressure was administered, with some improvement. Later that day, the trachea was electively intubated and methylprednisolone was administered. Cultures of the sputum grew candida species; blood cultures were negative.

On the 10th day at the other hospital, the patient was transferred by helicopter to this hospital (according to his family’s wishes) and admitted to the medical ICU. Medications at the time of transfer were fentanyl, midazolam, and norepinephrine by intravenous infusions, as well as vecuronium, imipenem, moxifloxacin, vancomycin, pantoprazole, ondansetron, methylprednisolone, sodium succinate, acetaminophen, enoxaparin, albuterol by nebulizer, fluticasone nasal spray, and nystatin suspension.

The patient had gout, for which he took indomethacin as needed. He had received an influenza vaccination earlier that season. He had no known allergies. He was married, had adult children, and lived in a semirural area of New England. He worked in manufacturing and had traveled for work to Indonesia and Japan during the month before this admission and to northern New England and the region surrounding the St. Lawrence River basin frequently during the previous year. His coworkers had not been ill. He reportedly did not participate in outdoor sports activities. He had a history of 40 pack-years of smoking and had stopped smoking 6 months before this admission; he drank alcohol infrequently and did not use illicit drugs. His mother and sister had _1-antitrypsin deficiency, his mother had chronic obstructive pulmonary disease, and his father had died at 63 years of age from myocardial infarction.

On examination, the patient was intubated, sedated, and afebrile. The blood pressure was 89/22 mm Hg, the pulse 50 beats per minute, and the respiratory rate 28 breaths per minute while he was receiving ventilatory support. There were coarse breath sounds bilaterally and diffuse 2+ edema of the arms and legs; the heart sounds and abdomen were normal. The plasma anion gap and results of serum protein electrophoresis were normal, as were blood levels of alanine aminotransferase, total and direct bilirubin, globulin, amylase, lipase, IgG, IgM, C3, and C4; other test results are shown in Table 1. Urinalysis revealed cloudy, yellow urine, with 1+ albumin and 2+ urobilinogen by dipstick. There were 5 to 10 red cells, 3 to 5 white cells, a few squamous cells, very few transitional cells, and very few renal tubular cells per high-power field, 20 to 100 hyaline casts and 20 to 100 granular casts per low-power field, and mucin.

Dr. Ackman: A chest radiograph that was obtained at the time of admission to this hospital revealed placement of endotracheal and esophagogastric tubes. There was a further increase in severe bilateral multifocal consolidation, without pneumothorax or definite pleural effusion (Figure 1D).

Dr. Hundemer: The fraction of inspired oxygen (Fio2) was increased to 1.00, and the partial pressure of arterial oxygen (Pao2) rose to 93 mm Hg, with an oxygen saturation of 95%. Methylprednisolone, meropenem, and continuous infusions of fentanyl, vasopressin, and propofol were administered; imipenem was discontinued. Gram’s staining of a sputum specimen revealed a moderate amount of polymorphonuclear leukocytes and no organisms; testing for antigens to adenovirus, parainfluenza, and respiratory syncytial virus was negative, as was nucleic acid testing for influenza A and B viruses.

Diagnostic procedures were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient's symptoms of myalgias, arthralgias, chills, fever, and upper respiratory symptoms, along with the development of severe pneumonia and acute hypoxemic respiratory failure, suggest a severe respiratory infection. The patient's history of travel to Indonesia and Japan, as well as his history of smoking, could have exposed him to various infectious agents. Despite treatment with multiple antibiotics, the patient's condition did not improve, suggesting a possible resistant or unusual pathogen. The patient's family history of \u03b11-antitrypsin deficiency could also suggest a predisposition to lung disease, although his own level of \u03b11-antitrypsin was within normal range. The presence of candida species in the sputum could suggest a fungal infection, but candida is also a common commensal organism and its presence does not necessarily indicate a fungal pneumonia. The patient's severe bilateral multifocal consolidation on chest radiograph is consistent with a severe pneumonia, but does not point to a specific etiology. Given the severity and persistence of the patient's symptoms despite broad-spectrum antibiotic treatment, a severe viral pneumonia, such as one caused by a novel or emerging virus, could be considered.\n\nDiagnosis: Severe viral pneumonia.""
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        ""content"": ""The patient's symptoms of myalgias, arthralgias, chills, fever, and upper respiratory symptoms, along with the development of severe pneumonia and acute hypoxemic respiratory failure, suggest a severe respiratory infection. The patient's condition did not improve despite treatment with multiple antibiotics, suggesting that the infection may be resistant to these drugs or caused by an atypical pathogen. The patient's history of travel to Indonesia and Japan, as well as his work in manufacturing, could potentially expose him to unusual pathogens. The patient's family history of _1-antitrypsin deficiency could potentially predispose him to lung disease, but his level of _1-antitrypsin was within the normal range. The patient's history of smoking could also contribute to his risk of respiratory disease. The patient's severe bilateral multifocal consolidation on chest radiograph is consistent with a severe pneumonia. The negative results for common respiratory pathogens suggest an atypical or unusual pathogen.\n\nDiagnosis: Severe pneumonia due to an atypical or unusual pathogen.""
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        ""content"": ""This is a 57-year-old man with a history of gout and a family history of _1-antitrypsin deficiency who presents with severe pneumonia and acute hypoxemic respiratory failure. His symptoms began with myalgias, arthralgias, chills, fever, and upper respiratory symptoms, which progressed to cough with blood-tinged sputum and pleuritic chest pain. Despite treatment with antibiotics, his symptoms persisted and worsened, leading to hospitalization and eventual transfer to the ICU. His chest radiographs showed severe consolidation in the left upper lobe and relatively mild consolidation in the right upper lobe, with further opacification of the left lung and worsening multifocal consolidation in the right lung over time. His sputum cultures grew candida species, but blood cultures were negative. \n\nThe differential diagnosis for this patient includes severe community-acquired pneumonia, hospital-acquired pneumonia, aspiration pneumonia, and pneumonia secondary to an atypical pathogen. Given the severity of his symptoms and the progression of his disease despite antibiotic treatment, an atypical pathogen or resistant organism should be considered. His recent travel to Indonesia and Japan also raises the possibility of a foreign or tropical pathogen. However, his family history of _1-antitrypsin deficiency, a condition that can lead to lung disease, could also be contributing to his severe respiratory symptoms. \n\nGiven the patient's severe pneumonia that has not responded to broad-spectrum antibiotics, the presence of candida species in the sputum, and the lack of improvement despite treatment, the most likely diagnosis is invasive pulmonary aspergillosis. This is a severe fungal infection that can occur in immunocompromised patients or those with chronic lung disease. The patient's family history of _1-antitrypsin deficiency could suggest underlying lung disease that predisposed him to this infection. \n\nDiagnosis: Invasive Pulmonary Aspergillosis.""
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 10.1056/NEJMcpc1406663,"Case 31-2015 — A 29-Year-Old Man with Thymoma, Diarrhea, and Weight Loss",,"Thymoma (types B2 and B3, clinical stage 4A), with associated cellular and humoral immunodeficiency (Good’s syndrome), autoimmune enteropathy, and pure red-cell aplasia.",Thymoma-associated cellular and humoral immunodeficiency (Good’s syndrome) and autoimmune enteropathy.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 29-year-old man with metastatic thymoma was seen in the outpatient oncology clinic of this hospital because of intractable diarrhea of 1 month’s duration.

The patient had received a diagnosis of thymoma at another hospital 5 years earlier, after a chest radiograph had been obtained to evaluate acute pain in the left shoulder.

Figure 1.

Imaging Studies.
Dr. Florian J. Fintelmann: The chest radiograph showed a large mediastinal mass and left pleural effusion (Figure 1A). Subsequent computed tomographic (CT) scans showed an anterior mediastinal soft-tissue mass that measured 10.0 cm craniocaudally, 10.1 cm transversely, and 5.0 cm anteroposteriorly (Figure 1B), as well as left pleural soft-tissue nodules, a pleural effusion, and associated atelectasis (Figure 1C). 18F-fluorodeoxyglucose positron-emission tomography revealed uptake in the mediastinal mass and left pleural nodules that was suggestive of pleural metastases. Magnetic resonance imaging (MRI) of the head was unremarkable.

Figure 2.

Pleural-Biopsy Specimen (Hematoxylin and Eosin).
Dr. Lawrence R. Zukerberg: Flexible bronchoscopy with video-assisted thoracoscopic evaluation of the left lung and pleural space was performed. Pleural-biopsy specimens showed nests of epithelioid tumor cells, some with numerous admixed lymphocytes separated by thick, hyalinized fibrous bands (Figure 2); these features are diagnostic of type B2 thymoma, with areas of type B3 thymoma. Flow cytometry revealed immature T cells that were consistent with thymocytes.

Dr. Blumenthal: Levels of human chorionic gonadotropin and alpha-fetoprotein were normal. A chemotherapy regimen of doxorubicin, cisplatin, vincristine, and cyclophosphamide was administered for three cycles, and then a thymectomy was performed.

Dr. Zukerberg: The resection specimen was a yellow, necrotic mass that measured 6.5 cm by 5.0 cm by 3.0 cm; no viable tumor was seen on microscopic examination. No measurable disease was present in the pleura.

Dr. Blumenthal: Thirteen months after the patient’s initial presentation, follow-up CT of the chest revealed new nodular left pleural thickening, a finding that was suggestive of metastatic disease. Thereafter, the patient was monitored with serial scanning. Approximately 2.5 years before this presentation, episodes of nonproductive cough developed that persisted for a few minutes at a time and were occasionally associated with vomiting and pain in the right lateral chest wall; there was no dyspnea at rest.

Dr. Zukerberg: Pathological examination of a core-needle biopsy specimen of the left pleura confirmed the presence of metastatic thymoma. A multiplexed polymerase-chain-reaction assay followed by single-base extension analysis revealed no mutations in any of the 68 tested loci from 14 cancer-associated genes (see the Supplementary Appendix, available with the full text of this article at NEJM.org).

Dr. Blumenthal: Additional chemotherapy with doxorubicin, cisplatin, vincristine, and cyclophosphamide was administered, followed by sunitinib; there was transient improvement in the cough. The treatment course was complicated by several episodes of fever and cough (at least three of which were documented as bacterial pneumonia) and intermittent oral thrush.

Six months before this presentation, treatment with an investigational agent — a selective inhibitor of phosphatidylinositol 3-kinase (PI3K) isoform _ — was begun. At the end of the second and fourth cycles of therapy, restaging scans showed stable disease. Four weeks before this presentation, at the end of the fifth cycle, diarrhea developed, and episodes increased in frequency to 10 to 12 liquid stools daily, each with an average volume of 250 ml; there was occasional nausea and vomiting, despite administration of loperamide hydrochloride, a solution of deodorized tincture of opium (10 mg of morphine equivalent per 1 ml of solvent), and diphenoxylate–atropine. Stool color reportedly varied in relation to oral intake; there was no abdominal pain, hematochezia, or melena.

Dr. Fintelmann: Thirteen days before this presentation, CT of the abdomen and pelvis revealed mild circumferential wall thickening of the sigmoid colon and prominence of the vasa recta, findings that were suggestive of inflammation (Figure 1D). Enlarging celiac lymphadenopathy was suggestive of progression of metastatic disease. CT of the chest that was performed on the same day revealed that the pleural and pulmonary nodules had not changed; these findings were consistent with stable thoracic metastases (Figure 1E).

Dr. Blumenthal: The blood uric acid level was 11.4 mg per deciliter (678 _mol per liter; reference range, 3.6 to 8.5 mg per deciliter [214 to 506 _mol per liter]). The investigational agent was stopped after a total of five cycles of therapy, without subsequent improvement in diarrhea. Six days later, 1 week before this presentation, testing of a stool specimen for Clostridium difficile was negative, and a stool culture did not grow any enteric pathogens.

One week later, the patient was seen in the outpatient oncology clinic of this hospital because of persistent diarrhea. He reported slight nausea without vomiting, fever, or chills, as well as poor appetite, increased fatigue, persistent chest-wall pain, nocturnal headaches, dyspnea when climbing stairs, and dryness of the lips and mouth and the skin of his hands. He had lost 9 kg of weight in the past month. Medications were allopurinol, a solution of deodorized tincture of opium (0.6 ml four times daily), hydromorphone, guaifenesin, diphenoxylate–atropine, potassium chloride, and, as needed, benzonatate for cough. He was allergic to vancomycin and omeprazole. He worked in a retail setting. He did not smoke, drink alcohol, or use illicit drugs. His paternal grandfather had had cancer, possibly of the prostate; other family history was noncontributory.

Table 1.

Laboratory Data.
On examination, the vital signs and oxygen saturation were normal. The abdomen was soft, with slight tenderness on deep palpation of the upper right quadrant and without guarding or rebound. The remainder of the examination was normal. The hematocrit, hemoglobin level, platelet count, and plasma anion gap were normal, as were the blood levels of glucose, total protein, albumin, globulin, magnesium, uric acid, phosphorus, total and direct bilirubin, alkaline phosphatase, and lactic dehydrogenase and results of renal-function tests. Nucleic acid testing for cytomegalovirus was negative; other test results are shown in Table 1.

Diagnostic procedures were performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 29-year-old man with metastatic thymoma was seen in the outpatient oncology clinic of this hospital because of intractable diarrhea of 1 month’s duration.

The patient had received a diagnosis of thymoma at another hospital 5 years earlier, after a chest radiograph had been obtained to evaluate acute pain in the left shoulder.

Figure 1.

Imaging Studies.
Dr. Florian J. Fintelmann: The chest radiograph showed a large mediastinal mass and left pleural effusion (Figure 1A). Subsequent computed tomographic (CT) scans showed an anterior mediastinal soft-tissue mass that measured 10.0 cm craniocaudally, 10.1 cm transversely, and 5.0 cm anteroposteriorly (Figure 1B), as well as left pleural soft-tissue nodules, a pleural effusion, and associated atelectasis (Figure 1C). 18F-fluorodeoxyglucose positron-emission tomography revealed uptake in the mediastinal mass and left pleural nodules that was suggestive of pleural metastases. Magnetic resonance imaging (MRI) of the head was unremarkable.

Figure 2.

Pleural-Biopsy Specimen (Hematoxylin and Eosin).
Dr. Lawrence R. Zukerberg: Flexible bronchoscopy with video-assisted thoracoscopic evaluation of the left lung and pleural space was performed. Pleural-biopsy specimens showed nests of epithelioid tumor cells, some with numerous admixed lymphocytes separated by thick, hyalinized fibrous bands (Figure 2); these features are diagnostic of type B2 thymoma, with areas of type B3 thymoma. Flow cytometry revealed immature T cells that were consistent with thymocytes.

Dr. Blumenthal: Levels of human chorionic gonadotropin and alpha-fetoprotein were normal. A chemotherapy regimen of doxorubicin, cisplatin, vincristine, and cyclophosphamide was administered for three cycles, and then a thymectomy was performed.

Dr. Zukerberg: The resection specimen was a yellow, necrotic mass that measured 6.5 cm by 5.0 cm by 3.0 cm; no viable tumor was seen on microscopic examination. No measurable disease was present in the pleura.

Dr. Blumenthal: Thirteen months after the patient’s initial presentation, follow-up CT of the chest revealed new nodular left pleural thickening, a finding that was suggestive of metastatic disease. Thereafter, the patient was monitored with serial scanning. Approximately 2.5 years before this presentation, episodes of nonproductive cough developed that persisted for a few minutes at a time and were occasionally associated with vomiting and pain in the right lateral chest wall; there was no dyspnea at rest.

Dr. Zukerberg: Pathological examination of a core-needle biopsy specimen of the left pleura confirmed the presence of metastatic thymoma. A multiplexed polymerase-chain-reaction assay followed by single-base extension analysis revealed no mutations in any of the 68 tested loci from 14 cancer-associated genes (see the Supplementary Appendix, available with the full text of this article at NEJM.org).

Dr. Blumenthal: Additional chemotherapy with doxorubicin, cisplatin, vincristine, and cyclophosphamide was administered, followed by sunitinib; there was transient improvement in the cough. The treatment course was complicated by several episodes of fever and cough (at least three of which were documented as bacterial pneumonia) and intermittent oral thrush.

Six months before this presentation, treatment with an investigational agent — a selective inhibitor of phosphatidylinositol 3-kinase (PI3K) isoform _ — was begun. At the end of the second and fourth cycles of therapy, restaging scans showed stable disease. Four weeks before this presentation, at the end of the fifth cycle, diarrhea developed, and episodes increased in frequency to 10 to 12 liquid stools daily, each with an average volume of 250 ml; there was occasional nausea and vomiting, despite administration of loperamide hydrochloride, a solution of deodorized tincture of opium (10 mg of morphine equivalent per 1 ml of solvent), and diphenoxylate–atropine. Stool color reportedly varied in relation to oral intake; there was no abdominal pain, hematochezia, or melena.

Dr. Fintelmann: Thirteen days before this presentation, CT of the abdomen and pelvis revealed mild circumferential wall thickening of the sigmoid colon and prominence of the vasa recta, findings that were suggestive of inflammation (Figure 1D). Enlarging celiac lymphadenopathy was suggestive of progression of metastatic disease. CT of the chest that was performed on the same day revealed that the pleural and pulmonary nodules had not changed; these findings were consistent with stable thoracic metastases (Figure 1E).

Dr. Blumenthal: The blood uric acid level was 11.4 mg per deciliter (678 _mol per liter; reference range, 3.6 to 8.5 mg per deciliter [214 to 506 _mol per liter]). The investigational agent was stopped after a total of five cycles of therapy, without subsequent improvement in diarrhea. Six days later, 1 week before this presentation, testing of a stool specimen for Clostridium difficile was negative, and a stool culture did not grow any enteric pathogens.

One week later, the patient was seen in the outpatient oncology clinic of this hospital because of persistent diarrhea. He reported slight nausea without vomiting, fever, or chills, as well as poor appetite, increased fatigue, persistent chest-wall pain, nocturnal headaches, dyspnea when climbing stairs, and dryness of the lips and mouth and the skin of his hands. He had lost 9 kg of weight in the past month. Medications were allopurinol, a solution of deodorized tincture of opium (0.6 ml four times daily), hydromorphone, guaifenesin, diphenoxylate–atropine, potassium chloride, and, as needed, benzonatate for cough. He was allergic to vancomycin and omeprazole. He worked in a retail setting. He did not smoke, drink alcohol, or use illicit drugs. His paternal grandfather had had cancer, possibly of the prostate; other family history was noncontributory.

Table 1.

Laboratory Data.
On examination, the vital signs and oxygen saturation were normal. The abdomen was soft, with slight tenderness on deep palpation of the upper right quadrant and without guarding or rebound. The remainder of the examination was normal. The hematocrit, hemoglobin level, platelet count, and plasma anion gap were normal, as were the blood levels of glucose, total protein, albumin, globulin, magnesium, uric acid, phosphorus, total and direct bilirubin, alkaline phosphatase, and lactic dehydrogenase and results of renal-function tests. Nucleic acid testing for cytomegalovirus was negative; other test results are shown in Table 1.

Diagnostic procedures were performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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        ""content"": ""The patient has a history of thymoma and is currently experiencing intractable diarrhea. The patient's diarrhea did not improve after stopping the investigational agent, suggesting that the diarrhea is not a side effect of the medication. The patient's stool tests for infectious causes were negative. The patient's CT scan showed inflammation of the sigmoid colon. The patient's blood tests were largely normal. Given the patient's history of thymoma, the diarrhea and colon inflammation could be due to paraneoplastic syndrome, a rare disorder triggered by an altered immune system response to a neoplasm. Paraneoplastic syndromes can cause a variety of symptoms, including gastrointestinal issues like diarrhea.\n\nDiagnosis: Paraneoplastic syndrome.""
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        ""content"": ""The patient is a 29-year-old male with a history of metastatic thymoma presenting with intractable diarrhea of 1 month's duration. The differential diagnosis for this patient includes infectious causes (such as Clostridium difficile, other bacterial infections, viral infections, or parasitic infections), medication side effects (particularly from chemotherapy or the investigational agent), inflammatory bowel disease, or a paraneoplastic syndrome related to his underlying cancer. The patient's stool has been tested for Clostridium difficile and other enteric pathogens, both of which were negative, making an infectious cause less likely. The patient's diarrhea did not improve after discontinuation of the investigational agent, making a medication side effect less likely. The patient does not have other symptoms suggestive of inflammatory bowel disease, such as abdominal pain or blood in the stool. The patient's CT scan showed mild circumferential wall thickening of the sigmoid colon and prominence of the vasa recta, which could be suggestive of inflammation, but without other symptoms of inflammatory bowel disease, this is less likely. Given the patient's history of metastatic thymoma, a paraneoplastic syndrome is a possibility. Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to a neoplasm. They are defined as clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease. In this case, the patient's intractable diarrhea could be a result of a paraneoplastic syndrome related to his underlying thymoma.\n\nDiagnosis: Paraneoplastic syndrome related to metastatic thymoma.""
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10.1056/NEJMcpc1415169,Case 30-2015 — A 50-Year-Old Man with Cardiogenic Shock,,"Myotonic dystrophy type 1, with associated cardiomyopathy, cardiac arrest, and generalized ischemia.",Adult-onset myotonic dystrophy type 1.,"Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP-BY-STEP DEDUCTION TO IDENTIFY THE CORRECT RESPONSE. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
This patient has oral ulcers, which can be associated with autoimmune and infectious diseases. The patient has a negative infectious work up and did not respond to antibiotics, which supports an autoimmune process. The patient has genital ulcers, which are associated with the autoimmune process of Behcet’s disease. Nodules of the legs further support an autoimmune process such as Behcet’s disease. Symmetric arthralgias are seen in a majority of patients with Behcet’s disease. Fever can be seen in systemic autoimmune processes such as Behcet’s disease. The rash is described as pustular, which can be seen in pathergy phenomenon, a highly specific sign for Behcet’s disease.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                 
A 50-year-old man was transferred to this hospital because of cardiogenic shock.

A diagnosis of dilated nonischemic cardiomyopathy had been made when the patient was in his late 40s. When he was 48 years of age, a dual-chamber pacemaker and implantable cardioverter–defibrillator (ICD) was placed.

Figure 1.

Transthoracic Echocardiograms.
Dr. Jodi L. Zilinski (Echocardiology): Four months before admission, transthoracic echocardiography revealed a left ventricular ejection fraction of 40% (Figure 1A, 1B, and 1C; and Videos 1 and 2, available with the full text of this article at NEJM.org).

Table 1.

Laboratory Data.
Dr. Herrington: Several days before admission, malaise, fatigue, increasing dyspnea, and chest tightness developed. One day before admission, the patient was seen by his primary care provider. The systolic blood pressure was reportedly between 80 and 89 mm Hg, the pulse higher than 100 beats per minute, and the oxygen saturation 77% while he was breathing ambient air. Emergency medical services were called; on examination, the patient’s mentation was normal, and the cardiac rhythm was rapid atrial fibrillation. During transport by ambulance to another hospital, ventricular tachycardia developed, and the patient became unresponsive and apneic. Cardiopulmonary resuscitation was begun, and the trachea was intubated. In the emergency department, blood levels of magnesium and alkaline phosphatase were normal; other test results are shown in Table 1. Ventricular tachycardia was followed by transient pulseless electrical activity, with hypotension, hypoxemia, hypercapnia, and acidosis. Oxygen, multiple external shocks, epinephrine, amiodarone, dopamine, and sodium bicarbonate were administered. After approximately 25 minutes, atrial fibrillation was restored, and the blood pressure rose to 98/20 mm Hg. Norepinephrine bitartrate, insulin, midazolam, cisatracurium, furosemide, fentanyl, vasopressin, sodium bicarbonate, magnesium, calcium gluconate, potassium chloride, potassium phosphate, heparin, and normal saline were administered. The patient was admitted to the intensive care unit (ICU).

Dr. Zilinski: Transthoracic echocardiography revealed a left ventricular ejection fraction of 15%, severe diffuse hypokinesis, regional wall-motion abnormalities, mild left ventricular dilatation, normal wall thickness, and moderate mitral regurgitation, without pericardial effusion.

Dr. Herrington: Chest radiographs reportedly showed increasing consolidation of the right middle and upper lobes. The patient was paralyzed, and mechanical ventilation was continued. Furosemide and chlorothiazide were administered for oliguria, and broad-spectrum antibiotic agents for presumed aspiration pneumonia; venoarterial extracorporeal membrane oxygenation (ECMO) was initiated for persistent hypoxemia. On the second day, the patient was transferred to this hospital and admitted to the ICU. Medications on transfer included norepinephrine, dopamine, fentanyl, midazolam, vasopressin, insulin, and cisatracurium.

The patient had muscle weakness that had begun approximately 15 years earlier, when increasing weakness of his hands developed. When the patient was 40 years of age, episodes of lightheadedness occurred; a diagnosis of paroxysmal atrial fibrillation was made, and prophylactic anticoagulation with warfarin was begun. When he was 41 years of age, he noted difficulty walking (with occasional stumbling), gripping and releasing tools, and climbing stairs and ladders. Electromyography, which was performed at another hospital, reportedly revealed brief-duration, low-amplitude, polyphasic motor-unit potentials. During the next 3 years, his symptoms worsened, and his left forearm was fractured after a fall.

On examination when the patient was 44 years of age, extraocular movements were normal, and mild bilateral ptosis, moderate bilateral facial weakness, and slight thinning of the temporalis muscles were present. His speech had a nasal quality, without dysarthria or tongue weakness. The muscle weakness was rated as 4 on the Medical Research Council (MRC) scale (which ranges from 0 [paralysis] to 5 [normal strength]) and involved the neck flexors, finger extensors, and intrinsic muscles of the hands; strength was normal in the proximal muscles of the arms. Muscle tone was normal throughout. After the patient firmly grasped the examiner’s hand, he had difficulty releasing his grip quickly. Tapping of the finger extensor muscles on the dorsal forearm and on the abductor pollicis in the thenar eminence produced muscle contractions that relaxed slowly. There was slight weakness of the hip flexor muscles, normal strength in the quadriceps and hamstrings, and weakness of the dorsiflexors (MRC score, 3+) and plantar flexors (MRC score, 4) of the feet. The patient was able to point to a target with his fingertip, perform the heel–knee–shin test, and carry out rapid, rhythmic tapping movements with his hands and feet. Vibration sense was mildly decreased in his toes. He rose from a chair without the use of his arms and had a high-stepping gait. Deep-tendon reflexes were hypoactive in the arms and absent at the ankles. Romberg’s sign was absent. Over the course of the next few years, weakness progressed. When the patient was 47 years of age, he had difficulty lifting 5-gallon buckets at work; examination reportedly revealed weakness of the neck flexors (MRC score, 4_), wrist and finger extensors (MRC scores, 4), and finger flexors and distal leg muscles (MRC scores, 3+) and normal strength in the deltoid, biceps, triceps, hip flexors, quadriceps, and hamstrings. Deep-tendon reflexes were absent.

The patient also had obstructive sleep apnea, sudden sensorineural hearing loss in the left ear (which had begun when he was 45 years of age and which was unresponsive to glucocorticoid therapy), hypertension, hyperlipidemia, morbid obesity, cholelithiasis (which had required cholecystectomy), problems with ejaculation, non–insulin-dependent type 2 diabetes mellitus, gastroesophageal reflux disease, depression, vitamin B12 and vitamin D deficiencies, and episodes of pneumonia that were thought to be related to aspiration. Medications that he was taking before this acute illness included warfarin, pravastatin, pioglitazone, metformin, ketoconazole, atenolol, citalopram, furosemide, pantoprazole, and bupropion (all daily), as well as a vitamin B12 supplement (monthly) and a vitamin D supplement (weekly). He reportedly had allergies to morphine, codeine, and tramadol. He was married and lived with his wife and children. He worked in a retail store. He drank alcohol occasionally and did not smoke. His father and one sister had an undefined neuromuscular problem. His father had had lung cancer, and his mother uterine cancer; both died when they were in their 70s. One of his children had scoliosis and a neuromuscular disorder similar to that of the patient.

On examination, the patient was sedated and paralyzed. Coarse breath sounds in the lungs and active bowel sounds were present. There was trace edema of both legs, and the abdomen was soft and nondistended. The pupils were sluggishly reactive; oculocephalic and corneal reflexes were absent. The arms and legs had minimal withdrawal and possible posturing. The blood levels of magnesium and amylase were normal; other test results are shown in Table 1. Sodium bicarbonate, insulin, glucose solution, and furosemide were administered, and urine output increased (450 mm3 of urine over a 2-hour period). A cannula was placed for distal perfusion, and ECMO was continued.

Figure 2.

Chest Radiograph.
Dr. Stacey Verzosa: A chest radiograph (Figure 2) showed bilateral diffuse consolidation that was most confluent in the left lower lung, an enlarged cardiac silhouette, bilateral layering pleural effusions, and the presence of medical devices, including a dual-chamber pacemaker and ICD and an ECMO catheter.

Dr. Herrington: Electroencephalography revealed alternation of low-amplitude bursts with near-complete suppression of cerebral activity. Continuous venovenous hemofiltration was begun, without improvement in neurologic function. Overnight, multiple units of red cells and fresh-frozen plasma were transfused, and albumin was administered. Heparin, insulin, vasopressin, and norepinephrine were administered. Results of a cosyntropin stimulation test were normal. On the second day, computed tomography of the head revealed no evidence of hemorrhage or mass lesions.

Dr. Zilinski: Repeat transthoracic echocardiography revealed severe diffuse left ventricular hypokinesis, with regional variation and a left ventricular ejection fraction of 13% (Figure 1D, 1E, and 1F; and Videos 3 and 4).

Dr. Herrington: Fentanyl and midazolam were discontinued, and hydrocortisone was administered, without improvement in the patient’s level of consciousness. Portable electroencephalography revealed generalized slowing with near-total suppression of cerebral activity and without evidence of epileptiform abnormalities. Additional laboratory test results are shown in Table 1. On the fifth hospital day, in consultation with the patient’s family, mechanical respiratory support was withdrawn and comfort measures were instituted; shortly thereafter, the patient died.

An autopsy was performed.
Rationale (REMEMBER TO USE STEP BY STEP DEDUCTION):
Diagnosis:","Read the initial presentation of a medical case below and determine the final diagnosis. Assume that all of the relevant details from figures and tables have been explained in the text. When providing your rationale, USE STEP BY STEP DEDUCTION TO CREATE A DIFFERENTIAL DIAGNOSIS AND THEN USE STEP BY STEP DEDUCTION TO DETERMINE THE CORRECT RESPONSE.. After you provide your rationale, provide a single, specific diagnosis for the case in less than 10 words.

Example Case:
A 25-year-old man was admitted to this hospital because of oral ulcers, rash, and odynophagia. The patient had been well until approximately 18 days before this admission, when mild sinus congestion developed. Sixteen days before this admission, repair of a labral tear of the right hip and femoroacetabular impingement was performed, after which naproxen was administered. Approximately 8 days before this admission, pharyngitis, odynophagia, fevers, chills, and night sweats occurred. Three days later (5 days before this admission), the patient was seen by his physician at an outpatient practice. On examination, the tonsils were enlarged and erythematous, with crypt abscesses and anterior cervical lymphadenopathy; the remainder of the examination was normal. Amoxicillin was administered. The next day, the patient’s temperature rose to 38.6°C. The following day (3 days before this admission), he returned to his physician’s office. The temperature was normal, and the remainder of the examination was unchanged. The patient continued to take amoxicillin; however, fevers recurred. The following day (2 days before this admission), he returned to his physician’s office again. There was cervical lymphadenopathy and pustular discharge on the tonsils but no evidence of peritonsillar abscess. Testing for heterophile antibodies was negative; results of renal- and liver-function tests were normal, as were blood levels of glucose, calcium, total protein, albumin, and globulin. Other test results are shown in Table 1. Amoxicillin–clavulanate was administered, and he returned home. Oral lesions, pain on swallowing, and scattered pustules on his face and trunk developed; the lesions progressed to involve his arms and legs. One day before this admission, the patient was seen by his physician for a fourth time. On examination, he appeared ill and lethargic; the temperature was 38.7°C, and there was a pustular rash on the face and torso. He was admitted to another hospital. The patient reported pain when swallowing that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Medications on admission were amoxicillin–clavulanate, acetaminophen–oxycodone, ibuprofen, and, at bedtime, melatonin. The temperature was 38.8°C, the blood pressure 147/82 mm Hg, the pulse 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The pharynx was erythematous, and the tonsils were erythematous and enlarged with crypt abscesses and a patchy exudate. There was bilateral anterior cervical lymphadenopathy. There was a pustule on the lower lip, as well as pustules with crusted centers and surrounding erythematous wheals involving the face, torso, arms, and legs. The lesions were dime-sized (approximately 18 mm in diameter) or smaller. The remainder of the examination was normal. Rapid testing of a pharyngeal specimen for streptococcal infection was negative, as was a monospot test for heterophile antibodies; the creatinine level and results of liver-function tests were normal. Other test results are shown in Table 1. Ampicillin–sulbactam, hydromorphone, viscous lidocaine, acetaminophen, ibuprofen, and morphine were administered. Blood cultures remained sterile. During the first day, the temperature rose to 39.0°C. The day after admission to the other hospital, examination by an infectious-disease consultant revealed severe exudative pharyngitis and ulcers mostly involving the upper and lower lips and anterior hard palate near the gumline. Pustular lesions mostly involved the face and back, although some were palpable on the right thigh; the palms and soles were not involved. At the request of the patient’s family, he was transferred to this hospital later that day. The patient reported fevers, headaches, mild sinus congestion, myalgias in both thighs and calves, tender nodules on his shins, perianal pruritus, constipation that had lasted for 3 days, and weight loss of approximately 3.5 kg during this illness. He had a history of acne that differed from his current facial lesions, as well as “cold sores” and genital erosions that resolved spontaneously and dysphagia and occasional hematemesis for which esophagogastroduodenoscopic examinations (performed 15 months and 4 months earlier) reportedly revealed a lower esophageal ring, esophageal erosions, and possible eosinophilic esophagitis. He had had varicella infection (chickenpox) as a child and a previous chlamydia infection. Hydrocodone reportedly caused vomiting. He lived with roommates, owned two dogs, and worked in an office; a coworker had recently had an upper respiratory tract infection. He drank alcohol and smoked marijuana. He had been sexually active with multiple partners in the past year, sometimes with unprotected intercourse. He had traveled to Hawaii many months earlier. His father had hypertension and ulcerative colitis, and his mother had diverticulitis. He was of Native American and western European ancestry. On examination, the temperature was 37.1°C, the blood pressure 144/87 mm Hg, the pulse 72 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. There were erythematous ulcers on the lips and hard palate, and the tonsils had white erosions on a red base. There was submandibular, cervical, and inguinal lymphadenopathy. There were scattered pink papules and plaques involving the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins that were tender on palpation and had no underlying fluctuance. The patient had an ulcer on the left side of the glans penis (2 to 3 mm in diameter), similar ulcers on the scrotum, and a left perirectal ulcer (1 cm in diameter) with surrounding erythema. There were no bullae, target lesions, or lesions on the palms or soles. The remainder of the examination was normal. Blood levels of glucose, calcium, phosphorus, magnesium, total protein, albumin, globulin, lactate dehydrogenase, and creatine kinase were normal, as were results of renal- and liver-function tests; other test results are shown in Table 1. Blood samples were obtained for culture. Urinalysis and a chest radiograph were normal. An electrocardiogram showed a normal sinus rhythm and nonspecific T-wave abnormalities. A diagnostic procedure was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
This is a young man who presents with oral ulcers, odynophagia, rash, and joint pains. He also has genital ulcers and fever. These findings support either an autoimmune or infectious process. The patient has a family history of autoimmune disease (father has Ulcerative Colitis) and infectious risk factors of unprotected sex and recent travel to Hawaii. The differential diagnosis for this patient includes sexually transmitted infections, Crohn’s disease, Behcet’s disease and Lupus. The patient’s urinalysis is normal, making chlamydia or gonorrhea less likely despite a history of unprotected sex. Furthermore, the rash described is pustular with papules and plaques of the trunk, thighs, and buttocks, as well as nodular of the shins without fluctuance. This is not the characteristic rash of Syphilis or Herpes simplex, removing sexually transmitted infections from our differential. The rash description is also not characteristic of lupus and the patient does not have evidence of kidney disease. The patient is also a young male. This makes Lupus less likely. The patient’s does not have diarrhea or gastrointestinal symptoms that would be consistent with Crohn’s disease, despite a family history of Ulcerative Colitis. This makes Crohn’s disease less likely. The constellation of oral ulcers, genital ulcers, and a pustular rash in a young male is concerning for Behcet’s disease. Furthermore, the patient’s other non-specific symptoms of rash, fever, and joint pains are supportive of an autoimmune process.
Diagnosis:
Behcet’s disease is the most likely diagnosis.
===
Case:                  
A 50-year-old man was transferred to this hospital because of cardiogenic shock.

A diagnosis of dilated nonischemic cardiomyopathy had been made when the patient was in his late 40s. When he was 48 years of age, a dual-chamber pacemaker and implantable cardioverter–defibrillator (ICD) was placed.

Figure 1.

Transthoracic Echocardiograms.
Dr. Jodi L. Zilinski (Echocardiology): Four months before admission, transthoracic echocardiography revealed a left ventricular ejection fraction of 40% (Figure 1A, 1B, and 1C; and Videos 1 and 2, available with the full text of this article at NEJM.org).

Table 1.

Laboratory Data.
Dr. Herrington: Several days before admission, malaise, fatigue, increasing dyspnea, and chest tightness developed. One day before admission, the patient was seen by his primary care provider. The systolic blood pressure was reportedly between 80 and 89 mm Hg, the pulse higher than 100 beats per minute, and the oxygen saturation 77% while he was breathing ambient air. Emergency medical services were called; on examination, the patient’s mentation was normal, and the cardiac rhythm was rapid atrial fibrillation. During transport by ambulance to another hospital, ventricular tachycardia developed, and the patient became unresponsive and apneic. Cardiopulmonary resuscitation was begun, and the trachea was intubated. In the emergency department, blood levels of magnesium and alkaline phosphatase were normal; other test results are shown in Table 1. Ventricular tachycardia was followed by transient pulseless electrical activity, with hypotension, hypoxemia, hypercapnia, and acidosis. Oxygen, multiple external shocks, epinephrine, amiodarone, dopamine, and sodium bicarbonate were administered. After approximately 25 minutes, atrial fibrillation was restored, and the blood pressure rose to 98/20 mm Hg. Norepinephrine bitartrate, insulin, midazolam, cisatracurium, furosemide, fentanyl, vasopressin, sodium bicarbonate, magnesium, calcium gluconate, potassium chloride, potassium phosphate, heparin, and normal saline were administered. The patient was admitted to the intensive care unit (ICU).

Dr. Zilinski: Transthoracic echocardiography revealed a left ventricular ejection fraction of 15%, severe diffuse hypokinesis, regional wall-motion abnormalities, mild left ventricular dilatation, normal wall thickness, and moderate mitral regurgitation, without pericardial effusion.

Dr. Herrington: Chest radiographs reportedly showed increasing consolidation of the right middle and upper lobes. The patient was paralyzed, and mechanical ventilation was continued. Furosemide and chlorothiazide were administered for oliguria, and broad-spectrum antibiotic agents for presumed aspiration pneumonia; venoarterial extracorporeal membrane oxygenation (ECMO) was initiated for persistent hypoxemia. On the second day, the patient was transferred to this hospital and admitted to the ICU. Medications on transfer included norepinephrine, dopamine, fentanyl, midazolam, vasopressin, insulin, and cisatracurium.

The patient had muscle weakness that had begun approximately 15 years earlier, when increasing weakness of his hands developed. When the patient was 40 years of age, episodes of lightheadedness occurred; a diagnosis of paroxysmal atrial fibrillation was made, and prophylactic anticoagulation with warfarin was begun. When he was 41 years of age, he noted difficulty walking (with occasional stumbling), gripping and releasing tools, and climbing stairs and ladders. Electromyography, which was performed at another hospital, reportedly revealed brief-duration, low-amplitude, polyphasic motor-unit potentials. During the next 3 years, his symptoms worsened, and his left forearm was fractured after a fall.

On examination when the patient was 44 years of age, extraocular movements were normal, and mild bilateral ptosis, moderate bilateral facial weakness, and slight thinning of the temporalis muscles were present. His speech had a nasal quality, without dysarthria or tongue weakness. The muscle weakness was rated as 4 on the Medical Research Council (MRC) scale (which ranges from 0 [paralysis] to 5 [normal strength]) and involved the neck flexors, finger extensors, and intrinsic muscles of the hands; strength was normal in the proximal muscles of the arms. Muscle tone was normal throughout. After the patient firmly grasped the examiner’s hand, he had difficulty releasing his grip quickly. Tapping of the finger extensor muscles on the dorsal forearm and on the abductor pollicis in the thenar eminence produced muscle contractions that relaxed slowly. There was slight weakness of the hip flexor muscles, normal strength in the quadriceps and hamstrings, and weakness of the dorsiflexors (MRC score, 3+) and plantar flexors (MRC score, 4) of the feet. The patient was able to point to a target with his fingertip, perform the heel–knee–shin test, and carry out rapid, rhythmic tapping movements with his hands and feet. Vibration sense was mildly decreased in his toes. He rose from a chair without the use of his arms and had a high-stepping gait. Deep-tendon reflexes were hypoactive in the arms and absent at the ankles. Romberg’s sign was absent. Over the course of the next few years, weakness progressed. When the patient was 47 years of age, he had difficulty lifting 5-gallon buckets at work; examination reportedly revealed weakness of the neck flexors (MRC score, 4_), wrist and finger extensors (MRC scores, 4), and finger flexors and distal leg muscles (MRC scores, 3+) and normal strength in the deltoid, biceps, triceps, hip flexors, quadriceps, and hamstrings. Deep-tendon reflexes were absent.

The patient also had obstructive sleep apnea, sudden sensorineural hearing loss in the left ear (which had begun when he was 45 years of age and which was unresponsive to glucocorticoid therapy), hypertension, hyperlipidemia, morbid obesity, cholelithiasis (which had required cholecystectomy), problems with ejaculation, non–insulin-dependent type 2 diabetes mellitus, gastroesophageal reflux disease, depression, vitamin B12 and vitamin D deficiencies, and episodes of pneumonia that were thought to be related to aspiration. Medications that he was taking before this acute illness included warfarin, pravastatin, pioglitazone, metformin, ketoconazole, atenolol, citalopram, furosemide, pantoprazole, and bupropion (all daily), as well as a vitamin B12 supplement (monthly) and a vitamin D supplement (weekly). He reportedly had allergies to morphine, codeine, and tramadol. He was married and lived with his wife and children. He worked in a retail store. He drank alcohol occasionally and did not smoke. His father and one sister had an undefined neuromuscular problem. His father had had lung cancer, and his mother uterine cancer; both died when they were in their 70s. One of his children had scoliosis and a neuromuscular disorder similar to that of the patient.

On examination, the patient was sedated and paralyzed. Coarse breath sounds in the lungs and active bowel sounds were present. There was trace edema of both legs, and the abdomen was soft and nondistended. The pupils were sluggishly reactive; oculocephalic and corneal reflexes were absent. The arms and legs had minimal withdrawal and possible posturing. The blood levels of magnesium and amylase were normal; other test results are shown in Table 1. Sodium bicarbonate, insulin, glucose solution, and furosemide were administered, and urine output increased (450 mm3 of urine over a 2-hour period). A cannula was placed for distal perfusion, and ECMO was continued.

Figure 2.

Chest Radiograph.
Dr. Stacey Verzosa: A chest radiograph (Figure 2) showed bilateral diffuse consolidation that was most confluent in the left lower lung, an enlarged cardiac silhouette, bilateral layering pleural effusions, and the presence of medical devices, including a dual-chamber pacemaker and ICD and an ECMO catheter.

Dr. Herrington: Electroencephalography revealed alternation of low-amplitude bursts with near-complete suppression of cerebral activity. Continuous venovenous hemofiltration was begun, without improvement in neurologic function. Overnight, multiple units of red cells and fresh-frozen plasma were transfused, and albumin was administered. Heparin, insulin, vasopressin, and norepinephrine were administered. Results of a cosyntropin stimulation test were normal. On the second day, computed tomography of the head revealed no evidence of hemorrhage or mass lesions.

Dr. Zilinski: Repeat transthoracic echocardiography revealed severe diffuse left ventricular hypokinesis, with regional variation and a left ventricular ejection fraction of 13% (Figure 1D, 1E, and 1F; and Videos 3 and 4).

Dr. Herrington: Fentanyl and midazolam were discontinued, and hydrocortisone was administered, without improvement in the patient’s level of consciousness. Portable electroencephalography revealed generalized slowing with near-total suppression of cerebral activity and without evidence of epileptiform abnormalities. Additional laboratory test results are shown in Table 1. On the fifth hospital day, in consultation with the patient’s family, mechanical respiratory support was withdrawn and comfort measures were instituted; shortly thereafter, the patient died.

An autopsy was performed.
Rationale (REMEMBER TO CREATE A DIFFERENTIAL DIAGNOSIS):
Diagnosis:","{
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